bluuebunny/crossref_metadata_2025 huggingface dataset:
No evidence of somatic aryl hydrocarbon receptor interacting protein mutations in sporadic endocrine neoplasia
Authors: Raitila A , Georgitsi M , Karhu A , Tuppurainen K , Mäkinen M J , Birkenkamp-Demtröder K , Salmenkivi K , Ørntoft T F , Arola J , Launonen V , Vahteristo P , Aaltonen L A
Published: October 2007

Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were recently observed in patients with pituitary adenoma predisposition (PAP). Though AIP mutation-positive individuals with prolactin-, mixed growth hormone/prolactin-, and ACTH-producing pituitary adenomas as well as non-secreting pituitary adenomas have been reported, most mutation-positive patients have had growth hormone-producing adenomas diagnosed at relatively young age. Pituitary adenomas are also component tumors of some familial endocrine neoplasia syndromes such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes. Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas. Here, we have analyzed 32 pituitary adenomas and 79 other tumors of the endocrine system for somatic AIP mutations by direct sequencing. No somatic mutations were identified. However, two out of nine patients with prolactin-producing adenoma were shown to harbor a Finnish founder mutation (Q14X) with a complete loss of the wild-type allele in the tumors. These results are in agreement with previous studies in that prolactin-producing adenomas are component tumors in PAP. The data also support the previous finding that somatic AIP mutations are not common in pituitary adenomas and suggest that such mutations are rare in other endocrine tumors as well.
The optimal imaging of adrenal tumours: a comparison of different methods
Authors: Ilias Ioannis , Sahdev Anju , Reznek Rodney H , Grossman Ashley B , Pacak Karel
Published: October 2007

Computed tomography (CT; unenhanced, followed by contrast-enhanced examinations) is the cornerstone of imaging of adrenal tumours. Attenuation values of <10 Hounsfield units on an unenhanced CT are practically diagnostic for adenomas. When lesions cannot be characterised adequately with CT, magnetic resonance imaging (MRI) evaluation (with T1- and T2-weighted sequences and chemical shift and fat-suppression refinements) is sought. Functional nuclear medicine imaging is useful for adrenal lesions that are not adequately characterised with CT and MRI. Scintigraphy with [131I]-6-iodomethyl norcholesterol (a labelled cholesterol analogue) can differentiate adrenal cortical adenomas from carcinomas. Phaeochromocytomas appear as areas of abnormal and/or increased uptake of [123I]- and [131I]-meta-iodobenzylguanidine (a labelled noradrenaline analogue). The specific and useful roles of adrenal imaging include the characterisation of tumours, assessment of true tumour size, differentiation of adenomas from carcinomas and metastases, and differentiation of hyperfunctioning from non-functioning lesions. Adrenal imaging complements and assists the clinical and hormonal evaluation of adrenal tumours.
Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues
Authors: Ulisse Salvatore , Baldini Enke , Toller Matteo , Delcros Jean-Guy , Guého Aurélie , Curcio Francesco , De Antoni Enrico , Giacomelli Laura , Ambesi-Impiombato Francesco S , Bocchini Sarah , D’Armiento Massimino , Arlot-Bonnemains Yannick
Published: October 2007

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.
The radiation response of hormone-resistant prostate cancer induced by long-term hormone therapy
Authors: Wu Chun-Te , Chen Wen-Cheng , Liao Shuen-Kuei , Hsu Cheng-Lung , Lee Kuan-Der , Chen Miao-Fen
Published: October 2007

Hormone therapy for prostate cancer eventually fails leading to a stage called hormone-resistant (HR) disease. To investigate the issue about the characteristics and the radiation response in HR prostate cancer, we established HR cell sub-lines, 22RV1-F and 22RV1-DF, from 22RV1 cells with androgen deprivation for 16 weeks, and obtained LNCaP-HR from LNCaP with long-term bicalutamide treatment. We examined their sensitivities to radiation therapy and the underlying mechanisms. In vitro and in vivo faster tumor growth rate was noted in the HR prostate cancer cells when compared with control. Moreover, HR prostate cancer cells had greater capacity to scavenge reactive oxygen species, and suffered less apoptosis and senescence, and subsequently were more likely to survive from irradiation as measured by clonogenic assay invitro and growth delay invivo. The decreased p53 and increased mouse double minute 2 oncogene (MDM2) might be the potential underlying mechanisms for the more aggressive growth and more radioresistance in HR prostate cancer cells. In conclusion, HR prostate cancer cells appeared to be more aggressive in tumor growth and in resistance to radiation treatment. Regulation of the expressions of p53 and MDM2 should be the promising treatment strategies for relative radioresistant prostate cancer.
The diagnosis and management of malignant phaeochromocytoma and paraganglioma
Authors: Chrisoulidou Alexandra , Kaltsas Gregory , Ilias Ioannis , Grossman Ashley B
Published: October 2007

Malignant phaeochromocytomas are rare tumours accounting for ~10% of all phaeochromocytomas; the prevalence of malignancy among paragangliomas is higher, especially those associated with succinate dehydrogenase subunit B gene mutations. Although a subset of these tumours has metastatic disease at initial presentation, a significant number develops metastases during follow-up after excision of an apparently benign tumour. Clinical, biochemical and histological features cannot reliably distinguish malignant from benign tumours. Although a number of recently introduced molecular markers have been explored, their clinical significance remains to be elucidated from further studies. Several imaging modalities have been utilised for the diagnosis and staging of these tumours. Functional imaging using radiolabelled metaiodobenzylguanidine (MIBG) and more recently, 18F-fluorodopamine and 18F-fluorodopa positron emission tomography offer substantial sensitivity and specificity to correctly detect metastatic phaeochromocytoma and paraganglioma and helps identify patients suitable for treatment with radiopharmaceuticals. The 5-year mortality rate of patients with malignant phaeochromocytomas and paragangliomas greater than 50% indicates that there is considerable room for the improvement of currently available therapies. The main therapeutic target is tumour reduction and control of symptoms of excessive catecholamine secretion. Currently, the best adjunctive therapy to surgery is treatment with radiopharmaceuticals using 131I-MIBG; however, this is very rarely curative. Chemotherapy has been used for metastatic disease with only a partial and mainly palliative effect. The role of other forms of radionuclide treatment either alone or in combination with chemotherapy is currently evolving. Ongoing microarray studies may provide novel intracellular pathways of importance for proliferation/cell cycle control, and lead to the development of novel pharmacological agents.
HER-2/neu transcriptionally activates Jab1 expression via the AKT/β-catenin pathway in breast cancer cells
Authors: Hsu Ming-Chuan , Chang Hui-Chiu , Hung Wen-Chun
Published: October 2007

Jab1 is a co-activator of activating protein-1 (AP-1) transcription factor and the fifth subunit of the constitutive photomorphogenesis 9 (COP9) signalosome, which has been shown to mediate nuclear exportation and ubiquitin-dependent degradation of the tumor suppressor p27Kip1. Jab1 is overexpressed in several types of human cancer. However, de-regulation of Jab1 gene expression in cancer cells is largely unclear. In this study, we reported that expression of Jab1 was stimulated by HER-2/neu oncogene via transcriptional activation. Promoter deletion and mutation analysis indicated that HER-2/neu stimulated Jab1 via the T cell factor (TCF) binding site located at the −380/−368 region of the human Jab1 promoter. DNA affinity precipitation assay and chromatin immunoprecipitation assay verified that binding of β-catenin and TCF-4 to this consensus site was increased by HER-2/neu. In addition, dominant-negative mutant of TCF significantly attenuated the stimulatory effect of HER-2/neu. We also demonstrated that HER-2/neu increased β-catenin/TCF-mediated Jab1 expression via the AKT signaling pathway because chemical inhibitor or dominant-negative mutant of AKT effectively attenuated the stimulatory action of HER-2/neu. IGF-I, which is a well-known AKT activator, also up-regulated the expression of Jab1 in NIH/3T3 and MCF-7 cells. Knockdown of Jab1 by small interfering RNA (siRNA) preferentially inhibited proliferation of HER-2/neu-overexpressing breast cancer cells. Taken together, our results suggest that HER-2/neu transcriptionally activates Jab1 expression to promote proliferation of breast cancer cells.
Risks of breast, endometrial, and ovarian cancers after twin births
Authors: Ji Jianguang , Fôrsti Asta , Sundquist Jan , Hemminki Kari
Published: October 2007

The concentrations of endogenous hormones differ between women with twin and singleton births, with a possible influence on the risk of cancer. We used the nationwide Swedish Family-Cancer Database, including 30 409 women with a twin birth, to examine the subsequent risks of breast, endometrial, and ovarian cancers. Relative risks (RRs) were calculated in a log-linear Poisson regression model of person-years as offset. Cancer data were retrieved from the Swedish Cancer Registry; a total of 1010, 210, and 174 women were diagnosed with breast, endometrial, and ovarian cancers respectively, after a twin birth. A significant decrease in the risk of breast cancer was noted among women with a twin birth compared with women with a singleton birth (RR 0.85, 95% confidence interval (CI) 0.74–0.98). The protective effects were observed throughout the intervals after last pregnancy and they were strongest shortly after the last pregnancy in women who delivered a twin birth before 30 years of age. Twin birth did not change the risk of endometrial cancer (1.08, 95% CI 0.79–1.47) but the RR was increased for women with the number of pregnancies ≥4 (1.39, 95% CI 1.11–1.76). The RR for ovarian cancer was 0.95 (95% CI 0.79–1.15). Our study showed that twin births significantly reduced the subsequent risk of breast cancer. However, the associations of twin births with endometrial and ovarian cancers were not substantial.
Valproic acid enhances tubulin acetylation and apoptotic activity of paclitaxel on anaplastic thyroid cancer cell lines
Authors: Catalano Maria G , Poli Roberta , Pugliese Mariateresa , Fortunati Nicoletta , Boccuzzi Giuseppe
Published: October 2007

The introduction of paclitaxel into multimodal therapy for anaplastic thyroid carcinoma has failed to improve overall survival. Toxicity rules out the high doses required, especially in older patients. The search for strategies to enhance paclitaxel antineoplastic activity and reduce its side effects is thus advisable. The study aimed to determine whether the histone deacetylase (HDAC) inhibitor valproic acid (VPA) improves the anticancer action of paclitaxel and elucidate the mechanisms underlying the effects of combined treatment. We examined the effect of VPA on the sensitivity to paclitaxel of two anaplastic thyroid carcinoma cell lines (CAL-62 and ARO), and the ability of the drug to determine tubulin acetylation and enhance paclitaxel-induced acetylation. The addition of as little as 0.7 mM VPA to paclitaxel enhances both cytostatic and cytotoxic effects of paclitaxel alone. Increased apoptosis explains the enhancement of the cytotoxic effect. The mechanism underlying this effect is through inhibition of HDAC6 activity, which leads to tubulin hyperacetylation. The results suggest a mechanistic link between HDAC6 inhibition, tubulin acetylation, and the VPA-induced enhancement of paclitaxel effects, and provide the rationale for designing future combination therapies.
Snail and Sonic Hedgehog activation in neuroendocrine tumors of the ileum
Authors: Fendrich Volker , Waldmann Jens , Esni Farzad , Ramaswamy Annette , Mullendore Michael , Buchholz Malte , Maitra Anirban , Feldmann Georg
Published: October 2007

The transcription factor Snail represses E-cadherin and induces epithelial–mesenchymal transition, a process also exploited by invasive cancer cells. Aberrant Hedgehog (Hh) signaling was recently observed in a variety of epithelial cancers and it has been shown that the Hh target gene Gli1 induces expression of Snail. In this study, we examined whether Snail and Sonic Hedgehog (SHH) are expressed in neuroendocrine tumors (NETs) of the ileum. Using immunohistochemistry, we found expression of Snail in 22 out of 37 (59%) of evaluated NET samples, but not in adjacent normal tissues. Snail expression was mostly restricted to the invasive front of the tumors. Six of seven liver metastases analyzed were positive for Snail. Intratumoral expression of SHH was detected in 27 out of 37 (73%) tumors. As opposed to Snail, cells expressing SHH were found to be distributed more randomly throughout the tumors. Out of 30 primary NETs, 16 (53%) showed both Snail and SHH expression. Furthermore, we found downregulation of E-cadherin in Snail-expressing cells by immunofluorescence. Real-time RT-PCR revealed conservation of the Hh target genes Gli1, Gli2, and Ptch in the pancreatic carcinoid cell line BON-1, which were downregulated upon Hh inhibition with cyclopamine. Moreover, Hh inhibition attenuated in vitro cell growth in a dose-dependent manner. In conclusion, we describe for the first time that Snail and SHH are overexpressed in a large subset of NETs of the ileum. Aberrant activation of these pathways might be involved in invasion and metastatic spread in NETs.
DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients
Authors: Jonkers Y M H , Claessen S M H , Perren A , Schmitt A M , Hofland L J , de Herder W , de Krijger R R , Verhofstad A A J , Hermus A R , Kummer J A , Skogseid B , Volante M , Voogd A C , Ramaekers F C S , Speel E J M
Published: October 2007

The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size ≥2 cm, Ki67 proliferative index ≥2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 non-insulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan–Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P≤0.0004) and tumor-specific death (P≤0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index ≥2% were reliable in predicting a poor tumor-free survival in non-insulinoma EPTs (P≤0.0181, whereas CK19 expression was the most optimal predictor of tumor-specific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in non-insulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.
Bicalutamide increases phospho-Akt levels through Her2 in patients with prostate cancer
Authors: Festuccia Claudio , Gravina Giovanni Luca , Muzi Paola , Pomante Roberto , Ventura Luca , Vessella Robert L , Vicentini Carlo , Bologna Mauro
Published: October 2007

Bicalutamide monotherapy is emerging as an alternative in the treatment of locally advanced prostate cancer. However, a significant number of these patients will recur and be in need of second-line therapies. The knowledge of molecular arrangements after pharmacological therapy seems to be a new primary prerequisite to predict the efficacy or the failure of a secondary therapy. Based on these considerations, we have conducted this study in order to analyze the expressions of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), Akt, epidermal growth factor receptor (EGFR), phospho-EGFR (p-EGFR), human EGFR2 (Her2), and phospho-Her2 (p-Her2) after bicalutamide treatment. For this purpose, we evaluated retrospectively 69 prostate cancer tissues derived from patients who received radical prostatectomy as the only treatment, and 81 from patients who received bicalutamide for 120 days before surgery. In addition, we analyzed at different time points the effects of castration performed on athymic mice bearing the LuCaP 35 xenograft line at different times. We observed that bicalutamide treatment increased significantly the levels of p-Akt, EGFR, and Her2 with a concomitant reduction in PTEN. This effect was time dependent and required of sufficient time to be evident as indicated by data obtained with the LuCaP 35 tumors. A logistic multiple regression analysis revealed that a switch of p-Akt control from a PTEN/EGFR- to Her2-after bicalutamide treatment was possible. Since Akt and Her2 can be associated with reduced drug sensitivity, our report suggests that the evaluation of molecular arrangements after bicalutamide treatment could be useful to identify subsets of patients who will be molecular permissive for new adjuvant anti-target therapies.
Bone metastases of differentiated thyroid cancer: impact of early 131I-based detection on outcome
Authors: Hindié Elif , Zanotti-Fregonara Paolo , Keller Isabelle , Duron Françoise , Devaux Jean-Yves , Calzada-Nocaudie Marie , Sarfati Emile , Moretti Jean-Luc , Bouchard Philippe , Toubert Marie-Elisabeth
Published: October 2007

Bone is the second most frequent target of distant metastases in patients with differentiated thyroid cancer, and such forms carry a very poor prognosis. The impact of 131I therapy in this setting is controversial. We describe the diagnostic circumstances and outcome of patients with bone metastases recently managed in two institutions. Among 921 consecutive thyroid cancer patients who had total thyroidectomy and 131I ablation between January 2000 and December 2004 and who were subsequently monitored, bone metastases had been diagnosed in 16 patients. In three cases, the bone metastases were non-functioning (negative 131I uptake) . These patients were treated with surgery and radiotherapy but progressed rapidly. The other 13 patients had functioning (positive 131I uptake) bone metastases. In five of them, thyroid cancer was revealed by signs of distant involvement (bone pain, n = 4; dyspnea, n = 1). The bone metastases progressed in these five patients, despite local therapy and multiple courses of 131I. The bone metastases in the remaining eight patients were discovered on the post-surgery 131I therapy scan. Complementary radiological studies were negative except in one patient in whom one of the metastases (a 5 mm lesion of the right humerus) was visible on magnetic resonance imaging (MRI). Six of these patients showed a good response to 131I therapy, with 131I uptake and Tg levels becoming undetectable or showing a sharp fall. One patient refused 131I therapy; bone metastases became visible on MRI within 1 year and the Tg level rose tenfold. The disease progressed in one patient despite 131I therapy. Post-surgical 131I ablation can contribute to early detection of bone metastases at a time when the Tg level may be only moderately elevated, when other radiological studies are negative, and when the disease is potentially curable by 131I therapy.
MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle
Authors: Visone Rosa , Russo Lucia , Pallante Pierlorenzo , De Martino Ivana , Ferraro Angelo , Leone Vincenza , Borbone Eleonora , Petrocca Fabio , Alder Hansjuerg , Croce Carlo Maria , Fusco Alfredo
Published: October 2007

We have recently reported that MicroRNAs (miR)-221 and miR-222 were up-regulated in human thyroid papillary carcinomas in comparison with the normal thyroid tissue. Bioinformatic analysis proposed the p27Kip1 protein, a key regulator of cell cycle, as a candidate target for the miR-221/222 cluster. Here, we report that the enforced expression of miR-221 and miR-222 was able to reduce p27Kip1 protein levels in thyroid carcinoma and HeLa cells in the absence of significant changes in specific p27Kip1 mRNA levels. This effect is direct as miR-221 and miR-222 negatively regulate the expression of the 3′-untranslated region-based reporter construct from the p27Kip1 gene, and is dependent on two target sites in this region. Consistent with these results, an enforced expression of the miR-221 and miR-222 induced the thyroid papillary carcinoma cell line (TPC-1) to progress to the S phase of the cell cycle. It is likely that the negative regulation of p27Kip1 by miR-221 and miR-222 might also have a role in vivo since we report an inverse correlation between miR-221 and miR-222 up-regulation and down-regulation of the p27Kip1 protein levels in human thyroid papillary carcinomas. Therefore, the data reported here demonstrate that miR-221 and miR-222 are endogenous regulators of p27Kip1 protein expression, and thereby, the cell cycle.
Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Cust Anne E , Kaaks Rudolf , Friedenreich Christine , Bonnet Fabrice , Laville Martine , Tjønneland Anne , Olsen Anja , Overvad Kim , Jakobsen Marianne Uhre , Chajès Véronique , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Linseisen Jakob , Lukanova Annekatrin , Boeing Heiner , Pischon Tobias , Trichopoulou Antonia , Christina Bamia , Trichopoulos Dimitrios , Palli Domenico , Berrino Franco , Panico Salvatore , Tumino Rosario , Sacerdote Carlotta , Gram Inger Torhild , Lund Eiliv , Quirós J R , Travier Noémie , Martínez-García Carmen , Larrañaga Nerea , Chirlaque María-Dolores , Ardanaz Eva , Berglund Göran , Lundin Eva , Bueno-de-Mesquita H Bas , van Duijnhoven Fränzel J B , Peeters Petra H M , Bingham Sheila , Khaw Kay-Tee , Allen Naomi , Key Tim , Ferrari Pietro , Rinaldi Sabina , Slimani Nadia , Riboli Elio
Published: October 2007

To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (RR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38–0.97), Ptrend = 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% CI 0.99–2.90), Ptrend = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% CI 1.46–4.66), Ptrend = 0.0006, Pheterogeneity = 0.13) and never-users of exogenous hormones (Pheterogeneity = 0.005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51–2.97)), which increased with the number of MetS factors (Ptrend = 0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (Pinteraction = 0.01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
Unrecorded Intangible Assets: Abnormal Earnings and Valuation
Authors: Kohlbeck Mark , Warfield Terry D.
Published: October 2007

We use the unique banking industry setting to demonstrate the impact of unrecorded intangible assets on abnormal earnings and equity valuation in the context of the residual income valuation model. We show that the persistence of bank abnormal earnings and, consequently, the pricing multiples on bank abnormal earnings, vary with the level of unrecorded intangible assets. Our evidence suggests that unrecorded intangible assets are important in understanding the persistence and valuation of abnormal earnings in the banking industry. The analysis framework introduced in this paper could also be used to examine the valuation impacts of intangible assets in other industries.
Standard-Setting Issues and Academic Research Related to the Accounting for Financial Asset Transfers
Authors: Schipper Katherine , Yohn Teri Lombardi
Published: October 2007

A large number and cross-section of firms undertake financial asset transfers. The Financial Accounting Standards Board and the International Accounting Standards Board have been grappling with the appropriate accounting for financial asset transfers, especially with respect to derecognition—that is, when the assets should be removed from the transferor's balance sheet. This paper discusses the financial reporting issues surrounding financial asset transfers and summarizes the related academic research. It also discusses potentially useful future research that could provide insights for standard-setters and suggests some impediments to that research.
Auditing Related Party Transactions: A Literature Overview and Research Synthesis
Authors: Gordon Elizabeth A. , Henry Elaine , Louwers Timothy J. , Reed Brad J.
Published: October 2007

We examine research relevant to auditing related party transactions to contribute to the PCAOB project on this topic and to provide other policy makers, auditors, and academics with an overview of relevant literature. Specifically, we report on the challenges associated with the identification, examination, and disclosure of related party transactions. Additionally, we address issues and research evidence related to nondisclosure and reliance on management assertions, risk assessment, materiality, fraud detection, the effect of related party transactions on corporate governance, and international auditing issues. Overall, we believe that the findings in academic research and the significance of related party transactions in recent prominent fraud cases are consistent with the PCAOB's reconsideration of auditing of related party transactions. We conclude with implications for further research.
Including Credit Standing in Measuring the Fair Value of Liabilities—Let's Pass This One to the Shareholders
Authors: Chasteen Lanny G. , Ransom Charles R.
Published: October 2007

Measuring and reporting liabilities at fair value is part of the FASB's overall project on fair value measurement and reporting. The FASB has taken the position that in measuring and reporting the fair value of a liability, such as a debt financial instrument, the fair value measure should reflect the credit standing of the issuer. Furthermore, changes in fair value, including the effect of changes in the issuer's credit standing, should be reported as gains and losses on the issuer's income statement. Whether liabilities should be reported at fair value and whether the fair value measure should incorporate credit standing and changes in credit standing are controversial issues. The primary controversy centers on the counterintuitive results of an entity's recording of a loss if its credit standing improves or a gain if its credit standing deteriorates. In this paper, we advocate an alternative position. We propose that liabilities be measured and reported using risk-free rates. This proposed approach recognizes the default risk portion of a debt's fair value as a distribution to shareholders when the liability is incurred. Our proposal supports the FASB's position that an entity's cost of borrowing, that is, interest expense on the entity's income statement, should reflect its credit standing and changes in its credit standing. We believe that our approach to accounting for liabilities is a viable alternative that warrants consideration. It avoids counterintuitive results, is consistent with the theories underlying the pricing of debt securities, and is more consistent with a going-concern assumption that an entity is expected to fulfill its debt obligations.
PCAOB Inspections of Smaller CPA Firms: Initial Evidence from Inspection Reports
Authors: Hermanson Dana R. , Houston Richard W. , Rice John C.
Published: October 2007

We examine 316 Public Company Accounting Oversight Board (PCAOB) inspection reports issued to smaller CPA firms (100 or fewer issuer clients) through July 2006. We find that 60 percent of the inspected firms have audit deficiencies. Firms with audit deficiencies are smaller, have a larger number of issuer clients, and are growing more rapidly than firms without deficiencies, suggesting an over-extension into the issuer client market by some firms. Deficiencies are more likely for inspections conducted in 2004 than 2005, and the PCAOB appears to have targeted smaller, riskier, rapidly growing audit firms for its 2004 inspections. In addition, we find some evidence that clients of deficiency firms are smaller, less profitable, and more highly leveraged. We also summarize the most common audit deficiencies and offer implications and directions for future research.
Auditor Communications with the Audit Committee and the Board of Directors: Policy Recommendations and Opportunities for Future Research
Authors: Cohen Jeffrey , Gaynor Lisa Milici , Krishnamoorthy Ganesh , Wright Arnold M.
Published: October 2007

To contribute to the Public Company Accounting Oversight Board (PCAOB) project on auditor communications with audit committees and boards of directors, we present in this paper a review of relevant academic literature. We also identify promising future research opportunities for the academic community. We specifically focus on how the communication process may affect overall financial reporting quality, internal controls, control environments, and external auditors' performance, as well as matters that potentially impact financial reporting and should interest the PCAOB (e.g., in the area of management discussion and analysis). We specifically link the findings from academic research to the discussion questions posed by the PCAOB in its 2004 briefing paper. Several potential implications of the findings should also interest standard-setters and regulators addressing issues related to corporate governance and financial reporting quality.
Reflections on Stewardship Reporting
Authors: O'Connell Vincent
Published: October 2007

Following the July 2005 decision by the IASB/FASB not to designate “stewardship” as a separate financial reporting objective in their converged Conceptual Framework, the purpose of this commentary is to call for a renewed emphasis on stewardship-related research in financial reporting. To this end, I propose specific questions related to the following themes: (1) the interaction between stewardship and decision-usefulness; (2) the contemporary meaning of stewardship; (3) changes in the importance of stewardship over time; (4) stewardship and corporate governance; and (5) stewardship and social and environmental reporting. The primary goal of the proposed research agenda is to better inform the debate about the wisdom of consigning the separate stewardship reporting objective to the realms of accounting history in those many nations where the converged IASB/FASB Conceptual Framework is likely to guide the future development of financial reporting standards.
Unfunded Public Employee Health Care Benefits and GASB No. 45
Authors: Keating Elizabeth K. , Berman Eric S.
Published: October 2007

The Government Accounting Standards Board (GASB) recently released Statement No. 45, Accounting and Financial Reporting by Employers for Post-Employment Benefits Other Than Pensions and its companion Statement No. 43 for pooled stand-alone health care plans, which will profoundly affect American governmental finance. The goal of this article is to encourage governments to consider carefully a full range of options in funding and restructuring other post-employment benefits (OPEB). This article will review Statement No. 45's potential impact on governments and review existing disclosures in financial reports as well as bond offering statements. The article will discuss the statement's impact on budgets and governmental operations, including collective bargaining. Funding options under Statement No. 45 will be detailed, including the advantages and disadvantages of irrevocable trusts and OPEB bonds. The article will also discuss the impact of Medicare Part D subsidies received by governments, as well as the bond rating implications of policy decisions surrounding OPEB. As the largest government entities are just now implementing GASB Statement No. 45, estimates of the magnitude of unfunded OPEB liabilities are limited as are the strategies likely to be adopted to cover these obligations. This article offers a summary of the unfunded OPEB liabilities reported by states and major cities and suggests some measures for assessing the ability of these entities to address these costs.
Disclosure, Incentives, and Contingently Convertible Securities
Authors: Marquardt Carol A. , Wiedman Christine I.
Published: October 2007

We present descriptive evidence on the quality of firms' disclosures related to contingently convertible securities (COCOs). We document evidence of inconsistent and inadequate disclosure of the information necessary to undo the financial reporting effects associated with COCOs prior to 2004, when only the general disclosure requirements on capital structure provided in SFAS 129 were in effect. Disclosure quality improved after the introduction of FASB Staff Position 129-a, which specifically required firms to disclose the terms of COCOs that would enable users to understand the conversion features of COCOs and their potential impact on earnings per share (EPS). However, we find evidence that managerial incentives significantly affect disclosure quality in both disclosure regimes. Our results underscore the difficulty that standard setters face in developing general disclosure guidelines that foster adequate disclosure and suggest that additional specific disclosure guidance may be necessary as new financial instruments and transactions evolve.
An Investigation of Auditor Perceptions about Subsequent Events and Factors That Influence This Audit Task
Authors: Janvrin Diane J. , Jeffrey Cynthia G.
Published: October 2007

Events that occur after the balance sheet date but before the audit report is signed and dated (subsequent events) may have a material effect on the financial statements and their users. New SEC reporting requirements reduce the time between the balance sheet and report dates, limiting the availability of subsequent event evidence. Professional groups, including the Canadian Institute of Chartered Accountants (CICA) and the American Institute of Certified Public Accountants (AICPA), question whether sufficient evidence will exist if subsequent event information is not available. They fear that decreased availability of subsequent event evidence may lower the quality of both audit judgments and financial reporting.

Scant prior research examines auditors' perceptions about subsequent events. Our study examines how auditors search for and discover subsequent event evidence and factors that influence this process. Responses from auditors representing all Big 4 firms and one national firm suggest that subsequent event evidence is important. Auditors generally follow procedures recommended by audit standards; however, recommended procedures uncover subsequent event evidence with low frequency. Implications for future research are discussed.
Recent Developments at the Securities and Exchange Commission: Academic Contributions and Opportunities
Authors: Jorgensen Bjorn N. , Linthicum Cheryl L. , McLelland Andrew J. , Taylor Mark H. , Yohn Teri Lombardi
Published: October 2007

In recent years, the Securities and Exchange Commission (SEC) has grown in size and scope. The implementation of Sarbanes-Oxley (SOX) and the globalization of accounting standards have increased the SEC's workload and brought forth important questions regarding the development and application of accounting and auditing standard setting and regulation. This paper identifies key issues of importance to the SEC including record levels of restatements, SOX implementation, the backdating of stock options, increased use of fair-values in financial reporting, adoption of IFRS by numerous non-U.S. registrants, and foreign deregistration. The article highlights the contribution of academic research as it relates to SEC speeches and rulemaking, drawing upon experience of 2005–2006 SEC academic fellows.
Board Oversight of Corporate Ethics Programs and Disclosure Transparency
Authors: Felo Andrew J.
Published: October 2007

For a number of years, groups such as the Jenkins Committee and the SEC have taken steps to make corporate activities more transparent to investors. In addition, the Sarbanes-Oxley Act requires publicly traded firms to disclose whether they have adopted codes of ethics for their senior financial officers. An implicit assumption is that ethics codes will help firms develop more transparent disclosure policies by enhancing their internal control environments. However, past research (Felo 2000) provides evidence that board involvement in the development, implementation, and maintenance of codes is an important factor in whether ethics codes are related to stronger internal control environments.

Using results from Standard and Poor's survey of transparency and disclosure (Patel and Dallas 2002), I find that firms having ethics programs overseen by their boards disclose more overall information, financial information, and board and management information than do other firms. Additionally, they are more likely to disclose information recommended by the Jenkins Committee and to voluntarily provide information recently mandated by the SEC. Although my evidence only demonstrates an association between board oversight of ethics programs and disclosure transparency, it does support mandating greater board involvement in corporate ethics programs as a way to enhance corporate disclosure transparency.
Animal Testing and Legitimization: Evidence of Social Investment and Corporate Disclosure
Authors: Savage Arline , Callaghan Joseph H.
Published: October 2007

Little research has been done concerning the disclosure of animal testing in annual reports. We posit that companies receive pressure from two groups to disclose animal testing practices: social/political activists and financial intermediaries (fund managers). We describe a legitimization framework culminating in corporate social disclosures on animal testing in annual reports and we use legitimacy theory to inform our empirical investigation of animal testing disclosures. The results reveal a significant increase in number and intensity of disclosures over the period considered. These disclosures also reflect a change in the nature of the underlying firm behavior in a manner consistent with legitimacy theory and predictions of our legitimization framework. We find that political/social activists appear to be more effective in their legitimizer role than financial intermediaries. Further, exploratory analyses reveal that some socially-responsible mutual fund managers invested in companies that perform animal testing, despite it allegedly being a screening criterion. In light of these findings, we suggest ways in which animal rights organizations could advocate to further improve corporate behavior with regard to animal testing.
Does Auditor Industry Specialization Matter? Evidence from Market Reaction to Auditor Switches
Authors: Knechel W. Robert , Naiker Vic , Pacheco Gail
Published: October 2007

Numerous capital market studies have investigated the stock market's reaction to firms switching to and from brand name auditors (Big 8/6/5/4 auditors). However, audit firm brand name is only one possible indication of the quality of an auditor. This study contributes to the existing literature on auditor switching, by examining how the market reacts to auditor switches to or from audit firms that are considered to be industry specialists. Consistent with our hypotheses, we find that firms switching between Big 4 auditors experience significant positive abnormal returns when the successor auditor is an industry specialist, and they experience significant negative abnormal returns when the successor auditor is not a specialist. We also find that these market reactions are more likely to be due to changes in perceived audit quality rather than differential costs of using specialist auditors. In supplemental analysis of switches involving non-Big 4 auditors, we find that firms that switch from a specialist Big 4 auditor to a non-Big 4 auditor suffer the largest negative market reaction. Surprisingly, we also observe that the market reacts most positively when a company switches from a non-Big 4 auditor to a Big 4 auditor who is not a specialist. These results suggest that the market does perceive audit quality differences based on industry specialization to be relevant to the valuation of a company's market value.
Auditors' Decisions on Audit Differences that Affect Significant Earnings Thresholds
Authors: Ng Terence Bu-Peow
Published: October 2007

I conduct an experiment to provide evidence on auditors' propensities to book (or waive) an audit difference that affects the client's ability to meet different earnings thresholds that are potential targets of clients' earnings management attempts. Results indicate that auditors have a higher propensity to book a quantitatively immaterial audit difference that affects the client's ability to meet recent earnings than one that affects the client's ability to meet analysts' expectations. However, these propensities are significantly lower than their propensity to book an audit difference (of the same nature and magnitude) that affects the client's ability to achieve positive earnings. I provide some evidence that the differences in auditors' decisions may be attributable to differential awareness of the different thresholds as well as to differential materiality and risk assessments. Auditors' propensity to book the audit difference decreases with its subjectivity, regardless of the earnings threshold affected. Further evidence suggests that the availability of explicit materiality guidance, which enhances auditors' awareness of the earnings thresholds, has the greatest impact in raising auditors' propensity to book an audit difference that affects the client's ability to meet analysts' expectations, followed by one that affects the client's ability to meet recent earnings, but not one that affects the positive earnings threshold.
The Impact of Roles of the Board on Auditors' Risk Assessments and Program Planning Decisions
Authors: Cohen Jeffrey R. , Krishnamoorthy Ganesh , Wright Arnold M.
Published: October 2007

Given governance breakdowns, an important issue is whether auditors are sensitive to a client's governance structure. The purpose of the study is to examine how the roles played by the board affect auditors' risk assessments and program planning decisions. An agency role of the board emphasizes monitoring corporate management while a resource dependence role focuses on helping a firm cope with environmental uncertainty, gain access to external resources, and establish sound business strategies.

Sixty-eight audit partners and managers evaluated a case where the roles of the board were manipulated: agency role (stronger or weaker) and resource dependence role (stronger or weaker). Results indicate that auditors' inherent risk assessments were not significantly affected by the resource dependence role, but control risk assessments were higher when the board played either a weak agency or weak resource dependence role than for the parallel strong condition. Further, audit program planning judgments were significantly affected by both the agency and the resource dependence variables. Finally, exploratory analysis indicates that when the board was stronger on both the agency and resource dependence dimensions, control risk assessments were the lowest and auditors decreased planned audit effort, while audit effort was increased for all other conditions.
The Effects of Client and Preparer Risk Factors on Workpaper Review Effectiveness
Authors: Asare Stephen K. , Haynes Christine M. , Jenkins J. Gregory
Published: October 2007

Both client risk and workpaper preparer risk are important contextual factors that reviewers must manage. In this study, we experimentally investigate how combined client risk and preparer risk impact workpaper review effort and accuracy. We found that reviewers allocated more effort when reviewing workpapers of a high-risk client, relative to a low-risk client, but preparer risk did not drive effort. With respect to review accuracy, we found that in a high client risk environment, reviewers were more accurate when preparer risk was high than when preparer risk was low. However, when client risk was low, review accuracy was invariant to preparer risk. These results suggest that although preparer risk is not a driver of review effort, it nevertheless can affect accuracy when client risk is high. Together, the results suggest that review effort does not appear to be the sole determinant of review accuracy.