bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 828: Progranulin is a good predictive biomarker in ovarian cancer patients followed in first remission
Authors: Han Jasmine J. , Yu Minshu , Hays John L. , Kohn Elise C.
Published: February 2011

Both secretory leukocyte protease inhibitor (SLPI) and progranulin (PGRN) are upregulated and overexpressed in ovarian cancers (OvCa). SLPI has important function in carcinogenesis as a proliferation and survival factor. PGRN is a potent growth and survival factor for cancer cells, and binds to SLPI, the complex of which protects PGRN from degradation by elastase. Recently, human epididymis protein 4 (HE4), located at the same whey acidic protein (WAP) genomic locus as SLPI and with similar structure, has been FDA approved for monitoring OvCa recurrence. We explored the application of SLPI and PGRN as monitoring biomarkers for OvCa recurrence. Archived plasma samples from 23 OvCa patients in first clinical remission, that had been collected prospectively every 3 months until relapse, were used to measure SLPI and PGRN concentrations; archival CA125 results and HE4 measured using commercially available ELISA were controls. Initial PGRN concentration, at study entry, was identified as a predictive factor. Thirteen of 23 patients had elevated PGRN concentrations and normal CA125 at the time of clinical remission. Eleven of those 13 patients recurred within 18 months (p= <0.03), with sensitivity and specificity of 79% and 78%, respectively. HE4 progressively increased in 19 of 23 patients, and 9 patients had positive change >12 months prior to the clinical progression. Only one patient maintained stable HE4 concentration and remains in remission; 3 patients who had stable HE4 concentrations relapsed at 14, 18, and 30 months. Five patients are still in clinical remission, but HE4 concentrations are increased in 4 of 5. In our small panel, HE4 had sensitivity and specificity of 77% and 10%, respectively. For the first time, our work evaluated SLPI and PGRN as predictive and monitoring biomarkers for OvCa recurrence. Additional study is needed to validate the usefulness of PGRN as a predictive factor in OvCa remission.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 828.
Abstract 829: A panel of three biomarkers for differentiating high from low grade neuroendocrine tumors of the lung: Findings from a Pilot Project
Authors: Nawaz Nava K. , Lin Fan , Stark Azadeh , Schuerch Conrad
Published: February 2011

Background: Distinguishing low/intermediate grade (carcinoid & atypical carcinoid) from high grade neuroendocrine carcinoma [small cell carcinoma & large cell neuroendocrine carcinoma (LCNEC)] of the lung can be difficult, especially in small biopsy specimens. This distinction is important for appropriate planning of a patient's course of treatment. Expression of biomarkers can be used to improve the precision of a differential diagnosis. We evaluated the expression of a panel of 5 biomarkers: CD117, a cytokine receptor, and KOC, a member of the insulin-like growth factor messenger RNA-binding protein family; Ki-67, a proliferation marker; the von Hippel-Lindau gene product (pVHL) and p16, 2 tumor suppresser markers. This panel was chosen because of their biological functions and their differential expression in low/intermediate vs. high grade cacinomas.

Method: We studied 42 consecutive cases of carcinoma of the lung (20 small cell carcinomas, 7 large cell neuroendocrine carcinomas, 12 carcinoids and 3 atypical carcinoids). Tissue microarrays were constructed and biomarkers’ expressions were evaluated immunohistochemically. Staining was standardized and scored as “0+” = Negative, “1+” = Focal, “2+” = 30-49% cells staining and “3+” = 50-100% cells staining positively. A specimen scored as “0” / “1+” was classified as negative, while a specimen scored as “2+” / “3+” was considered positive. The likelihood of expression of the panel by histopathologic diagnosis was estimated using two-sided non-parametric statistical techniques.

Results: Statistically significant differential expression for KOC, p16, pVHL and Ki-67 between low and high grade tumors was seen, but no significant difference for CD117 was detected. High grade tumors showed greater expression of Ki-67 (OR=13.85, 95% CI 3.34-57.47, p=0.0003), p16 (OR=3.52, 95% CI 1.75-7.11, p=0.0004) and KOC (OR=4.24, 95% CI 1.88-9.56, p=0.0005); while, pVHL expression was lower in high relative to low/intermediate grade tumors (OR=0.31, 95% CI 0.12-0.84, p=.022). We detected a statistically significant probability of the joint over-expression of 3 of the 5 biomarkers [p16 and KOC and Ki-67] in LCNEC relative to atypical carcinoids (OR=2.53, 95% CI 1.24-5.17, p=.011).

Conclusion: Findings suggest that Ki-67, KOC and p16 is an effective antibody panel in differentiating high from low/intermediate grade neuroendocrine carcinoma.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 829.
Abstract 83: A role of hepatic retinoid storage in diethynitrosamine-induced hepatic injury and hepatocarcinogenesis
Authors: Shirakami Yohei , Moriwaki Hisataka , Blaner William S.
Published: February 2011

The liver is the main tissue site of retinoid (vitamin A and its derivatives) storage in the body and the non-parenchymal hepatic stellate cell (HSC) is the major cellular site of retinoid storage within the liver. Lipid droplets of HSCs contain a number of bioactive metabolites including retinoids. Following liver injury, HSCs undergo a process known as activation. Loss of retinyl esters, the retinoid storage form, and lipid droplets from HSCs is one of the first events in the development of hepatic disease, leading progressively to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Although the loss of lipid droplets is a hallmark of HSC activation, whether it is a cause or consequence of the HSC activation process is unclear. Moreover, the contribution of the loss of hepatic retinoid storage to hepatic injury and hepatocarcinogenesis remains unknown. To investigate the role of hepatic retinoid storage and retinoid-containing lipid droplets in hepatic injury and hepatocarcingenesis, we studied diethynitrosamine (DEN)-induced HCC in lecithin:retinol acyltransferase (LRAT) knockout (KO) mice, which lack retinoid-containing lipid droplets in their HSCs, and in retinol-binding protein (RBP) KO mice, which are unable to mobilize hepatic retinoid stores. We measured a number of factors implicated in hepatic injury and cancer initiation. Using an acute hepatic injury model for investigating cancer initiation, assessment of mRNA levels by qRT-PCR of TNF alpha and TGF beta in livers of LRAT KO mice indicated that these mice were more susceptible to cancer initiation than WT mice. On the other hand RBP KO mice showed less susceptibility. LRAT KO mice showed higher levels of CYP26A1, a gene whose expression is known to be highly and directly responsive to retinoic acid level, suggesting that hepatic retinoic acid levels in LRAT KO mice were higher than that of WT, and that this may influence hepatic injury and carcinogenesis. Overall, our data suggest that hepatic retinoid storage can influence the progression of hepatic disease.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 83.
Abstract 831: uPAR Expression is Up-regulated in Cervical Cancer
Authors: Sasaki Toru , Nishi Hirotaka , Terauchi Fumitoshi , Higuma Chinatsu , Nagai Takeshi , Nagao Toshitaka , Isaka Keiichi
Published: February 2011

Hypoxia occurs during development of cervical cancer and is considered to correlate with its invasion. Hypoxia induces cancer cells to have more invasive property through the urokinase plasminogen activator receptor (uPAR) expression. Also, poor prognosis of uterine cervical cancer is correlated with hypoxic condition. Thus, we examined the relationship among the uPAR mRNA level and clinical prognostic factors, such as clinical and pathological stage, hemoglobin level, histologic type, tumor marker level and the effect on clinical outcome, using 66 cases of cervical cancer and 10 normal cervical tissues. These factors were evaluated by t test and Spearman's rank correlation coefficient. Survival analysis was performed using Kaplan-Meier curves. The uPAR mRNA level is significantly up-regulated in cervical cancers, compared with that in normal cervixes. The level of hemoglobin was significantly correlated with uPAR mRNA expression. Whereas, no other clinical prognostic factor had correlation with uPAR mRNA expression. Also, the uPAR mRNA level was not correlated with survival. According to the invasion assays, cervical cancer cell lines, CA and CaSki, under hypoxic condition (1% O2) showed more invasive property than those under normoxia. Hypoxia enhanced the endogenous uPAR mRNA level and protein expression by realtime RT-PCR and western blot analysis, respectively. Although we hypothesized that uPAR expression was correlated with tumor invasion and poor prognosis, the results revealed that uPAR mRNA expression was not correlated with survival nor most clinical factors except for the hemoglobin level. Although uPAR seems to be critical for the invasiveness in cervical cancer cell lines, uPAR may not be involved in cervical cancer invasion in vivo. Only real hypoxia may regulate the uPAR mRNA expression in cervical cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 831.
Abstract 839: HER2 expression occurs early in breast cancer dissemination
Authors: Ignatiadis Michail , Durbecq Virginie , Veys Isabelle , Rosari Jose , Criscitiello Carmen , Bedard Philippe , Singhal Sandeep K. , Buxant Frédéric , Chaboteaux Carole , Ghizlane Rouas , Larsimont Denis , Liebens Fabienne , Piccart Martine , Sotiriou Christos
Published: February 2011

Background: Systemic spread of disseminated tumor cells from the primary site may occur early in breast tumorigenesis. The role of HER2 in breast cancer (BC) dissemination is not well understood. We evaluated the expression of HER2 on peripheral blood Circulating Tumor Cells (CTCs) from women with various stages of breast cancer (BC).

Methods: 81 women with preinvasive breast lesions (Atypical Ductal Hyperplasia, Lobular Carcinoma In Situ and Ductal Carcinoma In Situ), 101 women with early invasive BC and 35 women with metastatic BC were included. CTCs were defined as Cytokeratin 8,18,19+/CD45-/DAPI+ cells detected using the CellSearch® technology. Any staining for HER2 on CTCs using the CellSearch® HER2 profiling kit was considered positive. HER2 detection was calibrated through peripheral blood spiking experiments with MCF7 and SKBR3 cells.

Results: > 1 CTCs/22.5mL of blood were detected in 6 of 81 (7%) women with preinvasive breast lesions (range 0-3 CTCs) and 15 of 101 (15%) women with early invasive BC (range 0-8 CTCs), whereas > 1 CTCs/7.5mL of blood were detected in 17 of 35 (49%) women with metastatic BC (range 0-1160 CTCs) (p<0.001). HER2 expression on CTCs was not associated with estrogen receptor (ER) and progesterone receptor (PR) expression or the histological grade of the primary tumor. In women with detectable CTCs, the ratio of HER2-positive CTCs/total CTCs was higher in HER2-positive than HER2-negative primary tumors (p=0.023). Despite a higher detection rate of CTCs, the ratio of HER2-positive CTCs/total CTCs was lower in metastatic BC (median 0.15, range 0-1.0) than in preinvasive (median 1.0, range 0-1.0) or early invasive BC (median 1.0, range 0.3-1.0) (p<0.001). Similar results were observed when only HER2-negative primary tumors were considered (p=0.004).

Conclusion: This is the first report showing that HER2-positive CTCs can be detected in women with preinvasive breast lesions, further supporting the hypothesis that dissemination occurs early in breast tumorigenesis. HER2 expression on CTCs is more commonly observed in earlier stages of breast cancer, suggesting that HER2 plays an important role in early dissemination. The EORTC 90091-10093 trial will test the hypothesis that trastuzumab can eliminate HER2-positive CTCs in patients with HER2-negative early breast cancer.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 839.
Abstract 843: Fast molecular response of marrow disease is highly prognostic in stage 4 neuroblastoma > 1 year
Authors: Stutterheim Janine , Zappeij-Kannegieter Lily , Versteeg Rogier , van der Schoot C. Ellen , Caron Huib N. , Tytgat Godelieve A.M.
Published: February 2011

Aim

Real-time quantitative (RQ)-PCR for detection of minimal residual disease (MRD) in children with neuroblastoma (NBL) can be used for evaluation of molecular bone marrow (BM) response. However its prognostic value still has to be established. We previously developed a panel of specific neuroblastoma RQ-PCR markers for MRD testing. The goal of this study was to determine whether sequential molecular assessment of BM using this panel of markers was prognostic for overall survival (OS).

Methods

In this single center study, RQ-PCR was performed with five NBL-specific markers: homeobox2b (PHOX2B), tyrosine hydroxylase (TH), dopamine decarbohydroxylase (DDC), growth associated protein 43 (GAP43) and cholinergic receptor3 (CHRNA3), on 106 retrospectively collected samples of 53 patients age > 1 year with metastatic disease. The prognostic impact of MRD at diagnosis (n=39), at 3 months after diagnosis (n=38) and after completing induction chemotherapy (n=29) was assessed using univariate and multivariate Cox regression analysis.

Results

At diagnosis, there was no correlation between tumor load in BM and outcome (Spearman's test, p=0.93). At 3 months after diagnosis, 29%(11/38) of the patients were in molecular BM remission, which was associated with favourable outcome (5-y-OS 62.3±15.0% versus 18.5±7.5%;p=0.009). After completion of induction chemotherapy, BM of 41%(12/29) of the patients was still MRD positive, which was associated with poor outcome (5-y-OS 0% versus 52.3±12,3;p<0.001). For both time points, the prognostic value of molecular response was an independent prognostic factor.

Conclusion

MRD detection measured by a panel of NBL specific-PCR targets could identify fast responders, who clear their BM early during treatment. Fast molecular response was an independent prognostic factor, associated with better outcome.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 843.
Abstract 847: LINE-1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer
Authors: Saito Kenichiro , Kawakami Kazuyuki , Matsumoto Isao , Oda Makoto , Watanabe Go , Minamoto Toshinari
Published: February 2011

Introduction: Non-small cell lung cancer (NSCLC) has a relatively poor prognosis and is a leading cause of cancer death worldwide. A substantial proportion of NSCLC patients suffer a recurrence following curative tumor resection, even when they have early stage disease. Molecular markers that are able to predict patient prognosis after surgery are therefore of clinical relevance, especially for early stage NSCLC. Global hypomethylation and the hypermethylation of gene promoter regions are common events in tumor DNA and are possible markers to predict clinical course of NSCLC patients. The aim of this study was to evaluate the prognostic significance of both global hypomethylation and gene promoter hypermethylation in DNA from NSCLC.

Methods: Genomic DNA was obtained from tumor tissue of 379 NSCLC patients who underwent surgery. Methylation levels were measured by real-time PCR following bisulfite modification of DNA and were correlated with clinicopathological parameters and patient prognosis. Methylation of long interspersed nuclear element 1 (LINE-1) was used as a surrogate marker for global methylation. Hypermethylation of the APC, CDH13 and RASSF1 promoter regions was also evaluated.

Results: Tumor tissue showed significantly higher CDH13 and RASSF1 methylation levels compared to normal lung tissue, but lower LINE-1 methylation levels. APC, RASSF1 and LINE-1 methylation levels were significant prognostic factors in univariate analysis of an initial cohort of 234 cases. APC and LINE-1 methylation remained significant prognostic factors in multivariate analysis that included age, gender, smoking history, histological type and pathological stage. LINE-1 methylation showed marginally significant prognostic value in stage IA and IB disease. To examine whether LINE-1 methylation was an independent prognostic factor, the study cohort was expanded to 364 cases. In sub-group analysis of stage IA cases with expanded cohort, survival was significantly worse for patients with LINE-1 hypomethylation. Multivariate analysis also revealed that LINE-1 methylation had significant prognostic value for stage IA NSCLC patients. Sub-group analysis failed to show prognostic value for LINE-1 methylation in all other NSCLC disease stages.

Conclusion: LINE-1 hypomethylation was an independent marker of poor prognosis in stage IA NSCLC. Validation of this finding in additional tumor cohorts could have clinical relevance for the management of early stage NSCLC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 847.
Abstract 848: VCAM-1 expression in epithelial ovarian cancer
Authors: Scalici Jennifer M. , Henretta Melissa , Slack-Davis Jill , Atkins Kristen
Published: February 2011

Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface adhesion molecule with known expression on the peritoneum of some advanced stage epithelial ovarian cancer patients. Previous study by our group has implicated VCAM-1 as a mediator of metastatic invasion of peritoneal surfaces by tumor cells in advanced disease, as inhibition of its function resulted in decreased tumor burden and improved overall survival in an animal model. We propose that VCAM-1 expression is a potential site of targeted therapy and in addition, expression may also serve as an early indicator of disease recurrence. We aim to correlate VCAM-1 expression with disease stage and histology to determine when in the course of disease expression begins. After IRB approval, archived tissue blocks from 1998-2008 containing samples of tumor, omentum, and peritoneum were evaluated for the presence of mesothelial cells. IHC staining of VCAM-1 was performed. Samples were evaluated and scored by a single pathologist blinded to stage and tumor type. All tissue samples from stage 1 patients were negative for VCAM-1 expression. The majority of samples from stages 3 and 4 were positive. Of the stage 2 samples, 50% were positive; those were primarily of serous histology. This suggests that there is an increase in peritoneal VCAM-1 expression as tumor cells leave the confines of the ovary and may serve as a marker of metastasis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 848.
Abstract 849: Detection of circulating micrometastasis in pancreatic cancer patients by immunomagnetic nanoparticles combined with RT-PCR
Authors: Zhou Jiahua , Hu Liang , Yu Zeqian , Zheng Jie , Yang Detong , Bouvet Michael , Hoffman Robert M.
Published: February 2011

By the time patients are diagnosed with pancreatic cancer, circulating cancer cells probably exist. Therefore, the detection of pancreatic tumor cells in the peripheral circulation could be used to diagnose early pancreatic cancer, which would otherwise not be detected by current imaging methods. The expression levels of h-TERT, CK20, CEA, and c-met were detected in a model of circulating micrometastasis in pancreatic cancer. The sensitivity and specificity of the measurements were evaluated. The expression of the above genes was subsequently measured in the circulation of pancreatic cancer patients. We compared their expression rate in pancreatic cancer patients at different stages to screen for the indicator with highest sensitivity and specificity in the detection of circulating pancreatic cancer cells. Immunomagnetic nanoparticles combined with RT-PCR enabled the detection of one tumor cell per 1×107 peripheral blood mononuclear cells. The positive expression rates of c-met, h-TERT, CK20, and CEA in the pancreatic cancer group were 80% (20/25), 100% (25/25), 84% (21/25), and 80% (20/25), respectively, while in the benign disease control group the rates were 0% (0/15), 0% (0/15), 6.77% (1/15), and 0% (0/15), respectively. There was a significant difference in the positive expression rate between the two groups (P<0.05). The specificity of h-TERT, CEA, and c-met was higher than that of CK20. The positive expression rate of the four genes was not related to gender, age, tumor size, CA-199 or CEA serum levels (P>0.05). However, the positive expression of c-met, CK20, and CE closely correlated with tumor stage (P<0.05). Immunomagnetic nanoparticles combined with RT-PCR were specific and sensitive for the detection of micrometastasis. The positive expression of c-met, h-TERT, CK20, and CEA in the circulation of pancreatic patients could be used as an indicator for circulating cancer cells. The detection rate of circulating cancer cells increased to 100% by the combined measurement of the four genes, suggesting the clinical utility of this approach.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 849.
Abstract 850: 32H2, a new diagnostic tool for HER2 CTFs
Authors: Palau Josep L. Parra , Peg Vicente , Escorihuela Marta , Mancilla Sandra , Arribas Joaquín
Published: February 2011

The tyrosine kinase receptor HER2 belongs to the Epidermal Growth Factor Receptor (EGFR) family and is amplified in 30% of breast cancer patients. These patients are currently treated with Herceptin (Trastuzumab), a monoclonal antibody against the extracellular domain of HER2.

A group of HER2 positive patients express a series of carboxy terminal fragments (CTFs) of the receptor. These patients have worse prognosis and are more likely to develop metastasis. In addition, CTFs positive patients are resistant to treatment with Herceptin.

Functional characterization of the different CTFs shows that only those containing the transmembrane domain are active. Furthermore, the CTF generated by alternative initiation of translation at Methionine 611, CTF-611, seems to be a hyperactive due to its ability to constitutively form dimers maintained by disulfide bonds. These hyperactive dimers specifically control the expression of genes causally involved in malignant transformation, providing a likely mechanism for the clinical observations made in patients expressing CTFs.

To date, the presence of CTFs in breast tumors have been studied by Western blot or by double immunoflourescence, using two antibodies, one targeting the intracellular domain and the other the extracellular domain of the receptor. However, both techniques are not able to distinguish between active and inactive CTFs. In addition, only careful comparison of the electrophoretic migration of the species found in tumor samples with those expressed in cell lines transfected with individual CTFs allows the identification of individual CTF. Obviously these techniques cannot be used to effectively determine the presence of active CTFs in large-scale clinical studies. Furthermore, given its hyperactivity, it would be useful to have a specific antibody against 611-CTF.

Here we present the generation and characterization of a monoclonal antibody that recognize specifically 611-CTFs. The low affinity of the antibody for the full-length HER2 may be explained by structural features of the antibody epitope. Using the antibody in a collection of paraffin embedded tumors, we were able to identify a subgroup in the HER2 positive tumors with worst clinical outcome.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 850.
Abstract 853: Prognostic significance of VEGF mRNA in pN0 patients with colorectal cancer
Authors: Wong SC Cesar , Lam Money YY , Ma Brigette BY , Au Thomas CC , Chan Charles ML , Hui Edwin P , Chan John KC , Chan Anthony TC
Published: February 2011

Objectives:

Recently, we discovered isolated cytokeratin 20 (CK20) positive cells in pN0 lymph nodes (LN) from patients with colorectal cancer (CRC) and molecular dissection of this micrometastasis pathway is essential for us to understand which metastasis-related mRNA genes are involved. Using tumor metastasis quantitative polymerase chain reaction (QPCR) arrays, vascular endothelial growth factor (VEGF) mRNA has the highest median fold change in CK20 positive pN0 LN when compared to CK20 negative pN0 LN from patients with CRC (AACR Infection and Cancer abstract number B47). In this study, we validate the QPCR array results by measuring VEGF mRNA concentration in an independent set of pN0 patients with CRC and examine the prognostic significance of VEGF mRNA in the same cohort of patients.

Materials and Methods:

Twenty-nine paraffin-embedded pN0 LN specimens with CK20 positive cells and the same number of specimens without CK20 positive cells from patients with CRC detected by immunostaining were retrospectively retrieved from the Department of Pathology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region. Total RNA was extracted from each sample for the quantification of VEGF mRNA using primers and a Taqman minor groove binder probe which labeled with a carboxyfluorescein reporter dye at the 5′-end and a nonfluorescent quencher at the 3′-end (Applied Biosystems, Foster City, USA). All 58 pN0 patients with CRC were follow-up for 48 months from their respective diagnosis for recurrent or metastatic CRC and a recurrent/metastatic curve was plotted using the median copy number of VEGF mRNA as the cut-off point.

Results:

The median concentration of VEGF mRNA in CK20 positive pN0 LN (35710 copy numbers, range: 5189-51240 copy numbers) was significantly higher than those in CK20 negative pN0 LN (1654 copy numbers, range: 210-4450 copy numbers) (p < 0.0001, Mann Whitney test). Using the median VEGF mRNA copy number (35710) of 29 CK20 positive pN0 patients with CRC as the cut-off point to plot the recurrent/metastatic curves, the time to recurrence or metastasis was significantly shorter for 14 patients with VEGF mRNA concentration > 35710 copy numbers (median recurrence/metastasis = 29.5 months) than for 15 patients with VEGF mRNA concentration ≤ 35710 copy numbers (p < 0.05, log-rank test).

Conclusions:

VEGF mRNA concentration is significantly correlated to the time of recurrence/metastasis and it may be able to predict the risk of recurrence/metastasis in pN0 patients with CRC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 853.
Abstract 854: Claudin-5 expression in tumor cells is a potential prognostic marker in pediatric ependymoma
Authors: Virág József , Baksa Gábor , Schaff Zsuzsa , Tímár József , Garami Miklós , Hegedũs Balázs
Published: February 2011

Ependymomas are common pediatric brain tumors that originate from the ependymal cell layer and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict clinical behavior. In a retrospective study, we performed the immunohistochemical analysis of 35 pediatric ependymomas for critical components of the cell-cell junctions including cadherins, claudins and occludins. Surprisingly, we found that a number of supratentorial but not infratentorial ependymoma expressed high levels of the brain endothelial cell tight junction component claudin-5 in tumor cells. Interestingly, this region specific expression pattern was also found in the choroid plexus epithelium of the lateral ventricles from tumor free neonatal tissue samples. Ultrastructural studies of human ependyma from various brain regions confimed that the observed protein expression pattern results in distinct regional differences in cell-cell junction organization and thus in ependymal barrier function. Nevertheless, we observed a significant increase in overall survival in patients bearing claudin-5 expressing ependymoma cells. These findings might - at least in part - be explained by the high expression cell-cell junction proteins that can interfere with the invasive capacity of tumor cells. Our data indicates that the assessment of claudin-5 expression in ependymoma cells is a potentially useful prognostic marker in this pediatric CNS malignancy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 854.
Abstract 855: Medication use and ovary cancer risk in the California Teachers Study
Authors: Duan Lei , Lacey James , Clarke-Dur Christina , West Dee , Bernstein Leslie , Henderson Katherine
Published: February 2011

Background: Approximately 21,000 new cases of ovarian cancer are diagnosed in the United States each year. Because inflammation is thought to affect ovarian carcinogenesis, non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, and other medications such as acetaminophen and histamine receptor antagonists, may affect the risk of ovarian cancer. However, existing epidemiological evidence on these associations is mixed.

Methods: We assessed the relationship between medication use and risk of invasive epithelial ovarian cancer in the California Teachers Study (CTS), a prospective cohort of former or current female public school teachers and administrators in California. Analysis included 104,184 women, of whom 420 were diagnosed with invasive epithelial ovarian cancer during follow-up through December 31, 2007. Self-reported medication use from the baseline CTS questionnaire (1995-1996) was used to classify exposures. Relative risks (RR) and 95% confidence intervals (CI) were obtained using Cox proportional hazards methods.

Results: Regular use, defined as at least once a week, of aspirin (RR 0.96; 95%CI 0.76 − 1.19), non-aspirin NSAIDs (RR 1.04; 95%CI 0.80 − 1.30), acetaminophen (RR 1.13; 95%CI 0.85 − 1.50) or histamine receptor antagonists (RR 0.85; 95%CI 0.58 − 1.20) was not associated with ovarian cancer risk. Ovarian cancer risk was not associated with daily use of aspirin (RR 1.04; 95%CI 0.77 − 1.45) or non-aspirin NSAIDs (RR 0.85; 95%CI 0.56 − 1.31) but was associated with daily use of acetaminophen (RR 1.82, 95%CI 1.01 − 2.95), and the latter association persisted after excluding ovarian cancers diagnosed during the first one to five years of follow-up. Two-thirds of the daily acetaminophen users also reported using acetaminophen for more than three years, but there was no association between increasing duration of use and ovarian cancer risk.

Conclusion: Our results do not support the hypothesis that these medications reduce the risk of ovarian cancer. Conversely, the finding that daily acetaminophen use was associated with increased risk of ovarian cancer differs from previous studies and may warrant further investigation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 855.
Abstract 860: Hypertension, diuretics, and antihypertensives in relation to bladder cancer
Authors: Jiang Xuejuan , Castelao J. Esteban , Yuan Jian-Min , Groshen Susan , Stern Mariana C. , Conti David V. , Cortessis Victoria K. , Coetzee Gerhard A. , Pike Malcolm C. , Gago-Dominguez Manuela
Published: February 2011

Background: The role of hypertension and/or antihypertensive medication use on bladder cancer risk is inconclusive. Given the high prevalence of hypertension in the United States, in the present study we investigated the relation between hypertension, antihypertensive drugs, and bladder cancer risk using a population-based case-control study conducted in Los Angeles County, California.

Methods: A population-based case-control study of bladder cancer was conducted in Los Angeles County from 1987-1999 and a total of 1586 age-, gender-, race- matched cases and neighborhood controls were included in the analyses. Participants were asked if they were told by a doctor that they had hypertension. They were also asked if they had taken any of the 21 brand names of diuretics and antihypertensive drugs listed in the questionnaire, which represented all the common prescription medications in these respective categories marketed in the US since the 1950s. Regular use was defined as taking a listed brand name drug two or more times a week for one month or longer. We asked regular users the ages at first and last use, duration of use, usual frequency and dosage of use, and the primary reason for such use.

Results: A history of hypertension was not related to bladder cancer; however, among hypertensive individuals, there was a significant difference in bladder cancer risk related to the use of diuretics or antihypertensive drugs (P for heterogeneity =0.003). Compared with individuals without hypertension, hypertensive individuals who regularly used diuretics/antihypertensives had a similar risk (odds ratio - OR, 1.05; 95% confidence interval − 95%CI, 0.86-1.29), while untreated hypertensive subjects had a 36% reduction in risk (OR, 0.64; 95% CI, 0.47-0.87). A greater reduction in bladder cancer risk was observed among current smokers (OR, 0.45; 95% CI, 0.28-0.72) and carriers of GSTM1 null (homozygous absence) genotypes (OR, 0.29; 95% CI, 0.16-0.54). Similarly, among smokers with GSTM1 null genotype, levels of 4-aminobiphenyl-hemoglobin adducts were significantly lower among untreated hypertensive individuals (45.7 pg/g Hb) compared to individuals without hypertension (79.8 pg/g Hb) (P = 0.009).

Conclusion: Our results suggest that untreated hypertension is associated with a reduced risk of bladder cancer, a finding that was partially supported by our biomarker data.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 860.
Abstract 862: Network patient navigation: An integrative, longitudinal model to reduce breast cancer disparities
Authors: Patierno Steven R. , LaVerda Nancy L. , Alexander Lisa M. , D. Ed , Levine Paul H. , Young Heather A. , Hoffman Heather J.
Published: February 2011

Introduction: Minority breast cancer mortality rates in Washington, DC are among the nation's highest. To address disparities we instituted the DC Citywide Patient Navigation Research Program (DC-PNRP) - an inter-institutional collaboration that is one of 9 National PNRP sites funded by NCI/ACS to evaluate the effectiveness of patient navigation in reducing barriers to obtaining health care while also addressing psychosocial factors.

Study Procedures: More than 1000 minority women have been enrolled from 7 recruitment sites at the point of suspicious finding to investigate whether patient navigation decreases time from suspicious breast finding to diagnostic resolution and time from diagnosis to treatment initiation. Utilizing a non-randomized design, concurrent, medical records-based controls have been identified. Data collection will extend through March 2010. A unique framework of “network navigation” emerged whereby services were integrated across a city-wide network of unaffiliated healthcare sites. Navigators from a broad partnership of clinical and community sites were trained to work collaboratively within a city-wide network to enroll patients in the study and assure each patient receives timely, quality care. This “integrative navigation” model is collecting data addressing not only structural barriers to access to care (i.e., inadequate insurance, lack of transportation, etc.), but also psychosocial barriers (i.e., fear, medical mistrust, acculturation, etc.). Frequent trainings, efforts that promote increased communication between navigators, and sharing of information about community resources were implemented to enhance care coordination and to assure appropriate referral strategies between community outreach, screening, and treatment sites.

Results and Conclusion: Implementation of DC-PNRP led us to broaden the original treatment-oriented navigation model to create a “Longitudinal Navigation” paradigm that follows the patient from outreach through survivorship. Data will be shown describing how this model addresses barriers to access and the underlying fragmentation of services that exist in DC for low-income uninsured or under-insured women. Data on the types and distribution of barriers will also be presented. This city-wide program serves as model for inter-institutional cooperation to improve health care access, particularly for the underserved.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 862.
Abstract 864: Correlates of mammography screening practice among immigrant women in Southern California
Authors: Shaheen Magda A. , Caro Blanca , Aman Yasser , Esfandiari Mahtash , Hulett Judie , Galal Osman
Published: February 2011

Introduction: Breast cancer (BC) is the most commonly diagnosed cancer among women in the United States. Immigrant underrepresented women are facing many challenges and barriers to knowledge, access to health care and preventive services. Few studies have examined factors associated with mammography screening among immigrant women in Southern California.

Purpose: We examined factors associated with mammography screening among immigrant women in Southern California.

Methods: A cross-sectional study of 517 immigrant women aged 40 years and older. The instrument included constructs from the Health Belief Model. The survey was conducted using a self administered questionnaire in the women's preferred language. The outcome variables were the percentage of women ages 40 and older who ever received a mammogram and the percentage of women who received a mammogram within the past year. Independent variables were demographics, frequency of visits to health care provider, and scores of the following variables: knowledge of BC symptoms and BC risk factors, perceived benefits, perceived health motivation and perceived barriers to obtaining a mammogram. We analyzed data using SPSS 15.

Results: of the 517 women, 50% were Iranian, 15% were Arab, and 21% were Asian/South Asian. Twenty eight percent had family history of BC, 63% had a friend diagnosed with BC, and 47% had yearly visit to the health care provider. Ever had a mammogram was reported by 88% of the women and 73% reported they had mammogram within the last 12 months. Participants had low knowledge of BC symptoms (mean score=7, Standard Deviation [SD]=3.5, range=1-13) and low knowledge of BC risk factors (mean score=8, SD=3.6, range=1-21). Women showed high health motivation (mean score=4.4, SD=0.6, range=1-5) and low barriers (mean score=2.4, SD=0.6, range=1-5). Predictors of ever had a mammogram were age, having a friend who was diagnosed with BC, and having a high score of health motivation. Factors associated with having a mammogram within the past year were having frequent visits to the health care provider, having a higher score in knowledge of BC symptoms, and having a lower score of perceived barriers to obtaining a mammogram.

Conclusions: The findings indicated that health care provider may influence the BC screening among immigrant women. There is a need for a culturally sensitive educational intervention to enhance the knowledge and awareness related to BC. This intervention can be provided through the health care provider and through the social support and family groups.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 864.
Abstract 865: Impact of race and health insurance on delays in breast cancer diagnosis and treatment in the District of Columbia
Authors: Hoffman Heather J. , Levine Paul H. , Patierno Steven R. , Young Heather A. , Alexander Lisa M. , LaVerda Nancy L.
Published: February 2011

Background: Delays in follow-up after breast cancer screening are thought to contribute to disparities in breast cancer outcomes. The primary objective of this study is to determine the impact of race as well as health insurance status on the diagnostic delay time, defined as the number of days from abnormal screening to definitive diagnosis. In addition, we analyze the effects of race and health insurance status on the treatment delay time, defined as the number of days from definitive breast cancer diagnosis to treatment initiation.

Methods: This is a retrospective study of 695 women examined for breast cancer between 1997 and 2009 at seven hospitals and clinics located in the District of Columbia. The outcomes of interest were the diagnostic delay time and the treatment delay time. We used full-factorial and main-effects ANOVA models to test for significant differences in these outcomes between African-American and white women with and without some type of health insurance.

Results: The mean diagnostic delay time was 37 days for insured white women, 76 days for uninsured white women, 75 days for insured African-American women, and 73 days for uninsured African-American women. In fitting a full-factorial ANOVA model, we found that insured white women had a significantly shorter delay in diagnosis than insured African-American women (p=0.0001) as well as uninsured white women (p=0.0007). Furthermore, a main-effects ANOVA model showed that after controlling for insurance status, African-American women had a mean treatment delay time of 45 days, which was significantly longer than the mean treatment delay time of only 17 days for white women (p<0.0001). Insurance status, however, had no significant effect on the treatment delay time after controlling for race (p=0.72).

Conclusions: Insured African-American women and uninsured white women waited more than twice as long to reach their definitive diagnosis than insured white women. African-American women also waited more than three times as long as white women for treatment initiation following definitive diagnosis. Lack of health insurance markedly decreased the speed of diagnostic resolution in white women, but having health insurance did not increase the speed of diagnostic resolution in African-American women. These results suggest that lack of health insurance may not be the primary barrier to optimal diagnostic resolution and treatment initiation in African-American women. It will be important to determine what other factors serve as the primary barriers, as well as if these delays affect the final breast cancer outcome for the patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 865.
Abstract 867: Oral contraceptive, menopausal hormone therapy use and risk of B-cell non-Hodgkin lymphoma in the California Teachers Study
Authors: Lu Yani , Sullivan-Halley Jane , Henderson Katherine D. , Ma Huiyan , Duan Lei , Wang Sophia S. , Lacey James , Chang Ellen T. , Deapen Dennis , Bernstein Leslie
Published: February 2011

Objective: To evaluate whether use of oral contraceptives (OC) or menopausal hormonal therapy (MHT) is associated with B-cell non-Hodgkin lymphoma (NHL).

Methods: Within the prospective California Teachers Study cohort, women under age 85 with no history of hematopoietic cancer were followed from 1995 through 2007 for diagnosis of B-cell NHL. Overall, 547 women of 116,779 women eligible for analysis of OC use and 402 of 54,758 postmenopausal women eligible for analysis of MHT use developed B-cell NHL. Relative risks (RR) and 95% confidence intervals (CI) were estimated by fitting multivariable Cox proportional hazards models.

Results: Women who used OCs had marginally lower risk of B-cell NHL than women who had never used OCs (RR=0.86, 95% CI=0.69-1.06). The reduced risk was most pronounced among women who started OCs before age 25, but did not decrease with increasing duration. No association with MHT was observed when MHT ever users were compared to the never users (RR=1.05, 95% CI=0.83-1.33); this result was consistent across formulations of MHT [unopposed estrogen therapy (ET), combined estrogen and progestin therapy (EPT)]. Among women who had never used MHT, women with a bilateral oophorectomy had three times greater risk than those with natural menopause (RR=3.15, 95% CI=1.62-6.13), whereas there was no association with bilateral oophorectomy among women who had used MHT. In stratified analyses according to hysterectomy and oophrectomy status, ET and EPT did not affect risk for women with natural menopause or those with hysterectomy who had at least part of an ovary remaining. Among women who had a bilateral oophorectomy, ET reduced risk of NHL (RR=0.41, 95% CI=0.21-0.82).

Conclusion: These data suggest that ET use decreases the risk of B-cell NHL among women with both ovaries removed, but not among women retaining at least part of an ovary. In other subgroups MHT does not influence risk.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 867.