bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 815: Relationship between altered expression levels of MIR21, MIR143, MIR145, and MIR205 and clinicopathologic features of esophageal squamous cell carcinoma(ESCC)
Authors: Makino Hiroshi , Ucida Eiji , Akagi Ichiro , Miyashita Masao , Nomura Tsutomu , Hagiwara Nobutoshi , Ishibashi Osamu , Takizawa Toshihiro
Published: February 2011

Background. In spite of the undisputed importance of altered expression patterns of miRNAs in various cancers, there is little information on the clinicopathologic significance of cancer-related miRNAs (i.e., MIR21, MIR143, MIR144, MIR145, and MIR205) in esophageal squamous cell carcinoma (ESCC).

Methods. We examined the expression levels of the precursor and mature miRNA genes in ESCC using Real-Time PCR. Furthermore, we investigated the relationships between the expression levels of these five miRNAs and the clinicopathologic parameters of ESCC patients.

Results. The expression levels of pre-MIR21 and pre-MIR144 were lower in ESCC than in the corresponding normal esophageal epithelium (p < 0.05). The expression levels of mature MIR21 and mature MIR145 were higher in ESCC than those in normal epithelium (p < 0.05). The mature/pre ratio of MIR21 in ESCC was higher than that in normal epithelium (p < 0.05). In the other cancer-related miRNAs, the mature/pre ratio followed a similar tendency to MIR21. Furthermore, altered expression of these miRNAs was related to the clinicopathologic features of ESCC patients. The high expression of mature MIR21 and mature MIR205 was associated with lymph node positivity in ESCC patients (p < 0.05). The high levels of expression of mature MIR143 and mature MIR145 were associated with recurrence of metastasis in ESCC patients (p <0.05).

Conclusions. The findings may imply that the processing of pre-miRNAs into mature miRNA is accelerated in ESCC. Analysis of the expression levels of miRNAs should provide useful information for evaluation of the staging, prognosis, and treatment of ESCC 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 815.
Abstract 817: KRAS and BRAF mutation spectrum in 1,035 FFPE tumor samples submitted for clinical testing
Authors: Bender Ryan P. , McGinniss Matthew J. , Dejesa-Jamanila Liza , Kuslich Christine
Published: February 2011

Activating mutations in both the KRAS and BRAF genes are associated with poor prognosis and non-response to anti-EGFR therapies in patients with advanced cancers. Clinical guidelines have recommended that KRAS mutational status be determined in all patients with metastatic colorectal cancer that are being considered for anti-EGFR therapies. In this study, a pathologist reviewed an H&E slide of each tumor sample and determined the percent tumor nuclei and percent necrosis. Each specimen was macrodissected and DNA was extracted. DNA was then amplified with primers flanking KRAS exon 2 (codons 12 and 13), and KRAS exon 3 (codon 61), and BRAF exon 15. Using the ABI3730 and Mutation Surveyor software, mutations were scored as positive when evident in both the forward and reverse reactions. Following analysis of the 1,035 clinical tumor specimens submitted to our lab for KRAS mutation analysis by direct sequencing, 387 or 37% had a mutation. Codon 61 mutations accounted for 18 of the 387 mutations identified, or 4.6%. Furthermore, four rare KRAS mutations were identified [G12dup, G12L, G13R and G13C]. These 22 mutations would not be detected by the commonly used clinical qPCR KRAS mutational analysis kits, as they are designed to identify only the 7 most common codon 12 and 13 mutations. Colorectal specimens accounted for 684 of the 1,035 samples in the study of which 286 or 41% of these had KRAS mutations. Of the 237 clinical specimens tested for BRAF exon 15 mutations, 28 or 12% had mutations. Of these, 26 were the common V600E mutation, but two were rare [c.1798_1799GT>AA (p.V600K) and c.1798_1799GT>AG (p.V600R)]. Both of the rare mutations were present in skin cancer samples. Colon specimens had a BRAF mutation rate of 10%, while skin specimens had a mutation rate of 61%. Mutational analysis of KRAS in tumor samples by direct DNA sequencing detects a greater variety of mutations in KRAS than kit-based qPCR assays, including mutations that affect codon 61. Based on the data presented omitting rare variants in codons 12 and 13 and omitting codon 61 would decrease the analytical sensitivity of KRAS mutational analysis to 94%.

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 817.
Abstract 820: Molecular markers for head and neck cancer detection
Authors: Pereira Lutecia , Reis Isildinha , Duncan Robert , Goodwin Jarrard , Franzmann Elizabeth
Published: February 2011

Introduction: Fifty thousand new cases of HNSCC are diagnosed in the United States each year. Unfortunately, most of these cases are advanced and only cured about 40% of the time. Cure rates could reach over 80% if diagnosed in earlier stages. We are developing a simple and inexpensive molecular screening test for the early detection of HNSCC. The markers under investigation are detectable in oral rinses and include soluble CD44 (solCD44), hyaluronic acid (HA) and total protein.

Materials and Methods: To study the population most likely to benefit from this early detection test, high-risk controls were identified by their smoking and/or drinking behavior from primary care clinics. They received a complete head and neck exam and had no clinical evidence of malignancy or premalignancy. Low-risk controls were normal volunteers. All subjects completed a detailed questionnaire including demographic, socioeconomic, risk factor and general health information. Oral samples were collected using a previously described swish and gargle method. We performed the solCD44, HA and protein assays in blinded fashion on oral rinses from 18 HNSCC cases, 18 frequency-matched high-risk controls and 21 low-risk controls using previously reported ELISA and ELISA-like assays.

Results: We statistically assessed the adequacy of matching between the cases and high-risk controls with respect to age, gender, race, socioeconomic status, tobacco and alcohol exposure and oral health. There were no significant differences between cases and controls for any of these variables except for a borderline significant difference in race. Log2solCD44 levels were significantly higher in cancer cases (2.42 ng/ml) and high-risk controls (2.12 ng/ml) compared to low risk controls (0.64 ng/ml, p<0.05). Log2protein levels were also higher in cancer cases (0.88 mg/ml) and high-risk controls (0.97 mg/ml) compared to low-risk controls (0.52, p<0.05). Following receiver operating curve analysis, the AUC for distinguishing high-risk controls from low-risk controls was 0.94 for solCD44 and 0.82 for protein. The AUC for distinguishing cancer from low-risk controls was 0.95 for solCD44 and 0.77 for protein. After adjusting for race, the AUC for distinguishing cancer from high-risk controls was 0.76 for solCD44 and 0.68 for protein. Both of these were better for the nonwhite group (0.84 for solCD44 and 0.83 for protein).

Conclusions: In this preliminary data set, the solCD44 and protein test appear to effectively distinguish HNSCC cases from high and low-risk controls. Race may have an impact on results. Further work including more subjects with longer follow-up must be done to confirm or refute these findings.

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 820.
Abstract 822: KRAS and BRAF mutation analysis using formalin fixed and paraffin embedded colorectal tissue and fine needle aspiration biopsies from thyroid
Authors: Meireles Sibele Inacio , Nakano Fabio E. , Consolin Luciane Choppa do Valle , Stiepcich Mônica Maria Ágata , Hoff Ana O. , Biscolla Rosa Paula Mello , Coudry Renata Almeida
Published: February 2011

Point mutations in codons 12, 13 and 61 of the KRAS gene and in codon 600 of the BRAF gene can be identified in neoplastic tissue from many different organs. KRAS mutations are present in approximately 40% of sporadic colorectal adenocarcinoma and this analysis is important to determine response to anti-EGFR targeted therapies. BRAF mutations are present in approximately 40% of the papillary thyroid carcinoma and 10% sporadic colorectal adenocarcinoma. BRAF mutation V600E is associated with more aggressive thyroid tumors and its detection is important for thyroid cancer prognosis. Detection of BRAF mutation in colorectal cancer is also useful for characterizing sporadic tumors. A method developed in-house to identify mutations in KRAS (codos 12 and 13) was validated using formalin-fixed paraffin-embeded tissue (FFPE) from 31 surgical specimens diagnosed with metastatic colorrectal cancer. Similarly, a method for BRAF mutation analysis (codon 600) was developed and validaded using 39 smears from fine needle aspiration biopsies (FNAB) of the thyroid. Cytology analysis was performed to confirm the presence of neoplastic or suspected lesions. DNA was extract from 1-4 slides containing the FFPE tissue sections or smears from the FNAB. Mutation analyses were performed by Sanger sequencing and results were compared with pyrosequencing. Automatic analysis of nucleotide sequences using the SeqScape software (Applied Biosystems) was also implemented. There was 85.7% and 100% concordance between Sanger sequencing and pyrosequencing for KRAS and BRAF mutation analysis, respectively. Precision intra- and inter-assay analysis were concordant, with the exception of one sample with KRAS mutation. Sensitivity was evaluated using pools containing different proportions of mutated and non-mutated DNA from cell lines. Data analysis by visual inspection resulted in the detection of the mutant allele in samples with at least 10% of mutated DNA. However, KRAS and BRAF mutations analysis using SeqScape software detected the mutant allele in pools containing at least 30% and 25% of mutated DNA, respectively. This is in accordance with the overall sensitivity observed by standard sequencing analysis. In conclusion, KRAS and BRAF mutation analysis can be successfully performed using small amount of tissue sections from FFPE specimens and smears from FNAB. This material has the advantage of requiring small amounts of sample and also allows cytology review of the tissue content prior to molecular analysis.

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 822.
Abstract 825: Development of RNA quality-control methods to improve tissue archiving and molecular diagnostic testing
Authors: Stanoszek Lauren M. , Crawford Erin L. , Blomquist Thomas , Willey James C.
Published: February 2011

Biospecimen collection and processing methods practiced today yield clinical samples with a wide variation in RNA quality. Efforts to improve these methods are inadequate due to insufficient means to measure RNA quality. Improved RNA quality control (QC) measurement methods will enable establishment of cut-off criteria to determine which biospecimens will yield reliable RT-PCR results. Implementation of such criteria will enable existing banks of samples with variable RNA quality to be used for reverse transcriptase polymerase chain reaction (RT-PCR)-based diagnostic test development. Sources of inter-sample variation in RNA quality include RNA integrity, genomic DNA (gDNA) contamination, and substances that either a) interfere with RT efficiency and/or b) carry over to cDNA and cause gene-specific inhibition of PCR efficiency. An RNA integrity reference model was established by incubating A549 cell line populations at room temperature for different amounts of time following cytolysis. Between 0 and 100 min. post cytolysis, ACTB degradation, as well as the degradation of other major housekeeping genes, was more rapid than decline in RNA Integrity Number (RIN) Score, a measurement based on microcapillary electropheresis. Quantification of single-copy CC10 gene gDNA in RNA controlled for gDNA contamination and measurement of transcript abundance of each gene relative to known number of respective cDNA internal standards controlled for PCR inhibitors. The RT inhibition test uses a Reverse Transcription Standards Mixture (RTSM) that contains a known number of copies of ERCC (External RNA Control Consortium) RNA and cDNA standards. A known quantity of RTSM is added to an RNA sample and measurement of PCR product from the RNA standard relative to its cDNA standard following RT-PCR assesses RT efficiency. These RT-PCR tests have been implemented on an Agilent 2100 Bioanalyzer® and are being developed for implementation on high throughput RT-PCR platforms such as the Biotrove OpenArray® nanoarray and the Gene Express Standardized Expression Measurement (SEM) Center™. Improved methods for biospecimen collection will be selected and will then be used to identify which samples collected according to present methods are suitable for analysis by RT-PCR-based molecular diagnostic tests.

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 825.
Abstract 827: Proximity-based c-MET activation assay development in formalin-fixed paraffin-embedded (FFPE) samples and profiling c-MET/HGF axis in human cancer-derived tumors
Authors: Rajiv Dua , Zhang Jianhuan , Parry Gordon , Winslow John , Penuel Elicia
Published: February 2011

Aberrant activation of membrane receptors frequently occurs in human carcinomas. Measurement of receptor phosphorylation is commonly used as an indicator of receptor activation in formalin-fixed paraffin embedded (FFPE) sections. This format is used to preserve human tissue samples and is the most common format for readily-available tissues from clinical trials and patient disease management. However, preservation of the labile phosphorylation signal is often inconsistent and consequently, results can be ambiguous. Here, we describe an alternative, novel approach to detect and quantify both receptor and ligand expression, as well as, activation status in FFPE samples. Specifically, we describe the development and validation of VeraTag based assays to measure total c-Met, total HGF and HGF/c-Met interactions. Using, the VeraTag technology, proximity-based assays, were used to detect and quantify c-MET, HGF, and HGF/c-MET interactions resulting from both exogenous and endogenous ligand stimulation in FFPE-prepared cell line pellets. The developed assays were subsequently used to profile human carcinomas including non-small cell lung, stomach, and head and neck tumors. Our data demonstrate a novel approach to detect and quantify c-Met activation which enables profiling and characterization of the c-Met activation status in FFPE human tissue samples. Furthermore, these data also demonstrate a basic approach to detect and quantify ligand-receptor interactions by VeraTag proximity-based assays that can be widely applied to measure activation of receptors in archived FFPE human tissue samples.

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 827.
Abstract 830: Clinical significance of measuring serum p53 antibodies in synchronous multiple colorectal cancer and double cancer patients
Authors: Kawamata Mayumi , Ota Mitsuyoshi , Fujii Shoichi , Ichikawa Yasushi , Suwa Hirokazu , Tatsumi Kenji , Watanabe Kazuteru , Yamagishi Shigeru , Akiyama, Hirotoshi , Ishikawa Takashi , Chishima Takashi , Shimizu Daisuke , Hasegawa Satoshi , Endo Itaru
Published: February 2011

Aims: The clinical significance of measuring serum p53 antibodies in colorectal cancer patients was evaluated.

Patients and Methods: Preoperative serum tumor markers including CEA, CA19-9 and p53 antibody were examined in 264 patients (stage I: 68, II: 73, III; 81) who were given diagnoses of colon and/or rectal cancer in Yokohama City University Hospital from 2007 to 2008. Correlativity of tumor markers to clinical findings was investigated.

Results: In the overall patients, range, median and positive ratio of each tumor marker are shown in Table 1. Positive ratio of CEA and CA19-9 gradually increased according to clinical stage of the tumor, however, those of p53 showed almost the same concentration in any stage. Then, in stage I patients, positive ratio of p53 was higher than CEA and CA19-9 (p=0.0005).

Thirty five cases (13.3%) of patients had synchronous or metachronous double or triple colorectal cancers. In that group, positive ratio of p53 was 48.3%, and median serum concentration of p53 was 0.915U/ml (0.15-295). Positive ratio and serum concentration of p53 of double or triple colorectal cancer patients were significantly higher than that of single cancer patients (p=0.0375).

Conclusions: Serum concentration of p53 is sensitive, especially in early stage of colorectal cancer compared with other tumor markers. Colorectal cancer patients who showed high concentration of p53 have to be carefully checked for occult 2nd gastrointestinal tumor.1 nnCEA(ng/ml)CA19-9(ng/ml)p53 antibody(U/ml)Range (median)overall2640.3-3371(2.95)1-18927(12)0.15-443(0.53) Stage0180.3-5.7(1.45)1-44(9)0.15-2.36(0.28) StageI680.3-18.3(1.7)1-161(10)0.15-233(0.45) StageII730.5-148.1(3.9)1-1353(13)0.15-435.5(0.775) StageIII810.7-124.4(3.5)1-345(14)0.15-136.2(0.645) StageIV251.8-3371(23.9)1-18927(31)0.15-443(0.58)  nCEA(%)CA19-9(%)p53 antibody(%)Positive ratiooverall26432.214.835.2 Stage0185.65.616.7 StageI687.45.929.4 StageII7337.012.341.1 StageIII8137.016.038.3 StaIV2588.048.036.0

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 830.
Abstract 833: Effects of ERCC2 and ERCC4 genetic polymorphisms on survival of patients with esophageal cancer
Authors: Lee Jang-Ming , Yang Shi-Yi , Yang Pei-Wen , Chuang Tzu-Hsuen , Chen Jin-Shing , Hsu Hsao-Hsun , Huang Pei-Ming , Lee Yung-Chie
Published: February 2011

Effects of ERCC2 and ERCC4 genetic polymorphisms on survival of patients with esophageal cancer

Jang-Ming Lee1; Shi-Yi Yang2; Pei-Wen Yang1; Tzu-Hsuen Chuang 1; Jin-Shing Chen1; Hsao-Hsun Hsu1; Pei-Ming Huang1; and Yung-Chie Lee1. 1Department of Surgery, National Taiwan University Hospital; 2Graduate Institute of Epidemiology, National Taiwan University, Taipei

Background: XPD/ERCC2 (ERCC2) and XPF/ERCC4 (ERCC4) are the genes involved in nucleotide excision repair (NER). The clinical roles of the genetic polymorphism of ERCC2 on R156R (rs238406) and rs3136038 within ERCC4 promoter region in esophageal cancer are unknown.

Methods: We evaluated 400 patients with esophageal cancer collected from 1996 to 2009 at National Taiwan University Hospital. The genotypes of ERCC2 on R156R and ERCC4 on rs3136038 within promoter region were analyzed with the TaqMan assay from the genomic DNA of peripheral leukocytes. The results of the genotyping were correlated to the survival of the patients.

Results: There is no significant difference in clinical characteristics among the enrolled patients among different genotypes of ERCC2 and 4. The C/C genotype of ERCC2 R156R shows an insignificant unfavorable progression-free survival (PFS) compared to other genotypes (A/A or C/A) (adjusted [HR] = 1.17, 95% CI=0.90-1.51, P=0.236). The ERCC4 rs3136038 G/A genotype displays significant association with worse PFS compared to other genotypes (A/A or G/G) (adjusted [HR] = 1.29, 95% CI=1.02-1.62, P=0.033). Combining these two polymorphisms, these two unfavorable genotypes (C/C on ERCC2 R156R and G/A on ERCC4 rs3136038) display dose-dependently to associate a worse overall and progression free survival with a significant HR of death and disease progression in the patients with both of the unfavorable genotypes comparing with those who without (adjusted [HR] = 1.49, 95% CI=1.04-2.15, P=0.031 for overall survival[OS]; adjusted [HR] = 1.57, 95% CI=1.09-2.26, P=0.015 for progression free survival [PFS]). Kaplan-Meier survival curves demonstrated a significant different distribution of OS and PFS between all patients by the number of unfavorable genotypes of ERCC2 and 4. (P=0.049 for OS and P=0.040 for PFS).

Conclusion: Our study demonstrated that the genetic variants of ERCC2 and ERCC4 may play a role for the clinical outcome in ECa patients. The patients of esophageal cancer with both C/C on ERCC2 R156R and G/A on ERCC4 rs3136038 may require closer follow-up after treatment.

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 833.
Abstract 834: IGF-II promoter specific methylation patterns are associated with its expression and disease progression in epithelial ovarian cancer
Authors: Lu Lingeng , Katsaros Dionyssios , Qian Biyun , Preti Mario , Menato Guido , Beeghly Alicia , Yu Herbert
Published: February 2011

Purpose: High insulin-like growth factor-II (IGF-II) expression in epithelial ovarian cancer is associated with aggressive disease and poor prognosis. IGF-II expression is regulated by promoter methylation; aberrant methylation is common in cancer. The effect of promoter methylation on IGF-II expression and the role of methylation in ovarian cancer are investigated in a clinical study.

Patients and Methods: The study enrolled 211 epithelial ovarian cancer patients who were followed after surgery for disease outcomes. Fresh tumor samples were collected from the patients and were analyzed for IGF-II promoter methylation using methylation-specific PCR, as well as for IGF-II mRNA expression with qRT-PCR. IGF-II peptide concentrations were measured with an ELISA kit in tumor tissues.

Results: The study found different levels of methylation in 3 IGF-II promoters (P2-P4) which are located in a large CpG island, high methylation in P2 (64.2%) and P3 (52.1%) and low in P4 (9.8%). Promoter-specific mRNA expression was lower in methylated than in unmethylated tumors. P3 methylation and expression appeared to play a major role for IGF-II in ovarian cancer. While methylation in individual promoter was not related to the disease, a methylation pattern between P2 and P3 was significantly associated with clinical and pathological features of ovarian cancer, including tumor grade, debulking results, residual tumor size and treatment response. The methylation pattern was also linked to disease progression, but not overall survival.

Conclusions: Our findings suggest that IGF-II expression affects tumor progression and the expression is regulated by methylation which may have clinical implications in disease management.

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 834.
Abstract 837: Genetic alterations in PIK3CA, AKT2 and PTEN gene associated with poor clinical outcome in oral squamous cell carcinoma
Authors: Huang Shiang-Fu , Chen I-How , Liao Chun-Ta , Wang Hung-Ming , Hsieh Ling-Ling
Published: February 2011

The PI3K/AKT pathway plays a fundamental role in the regulation of cell growth, division, survival, and, when disarranged, tumorigenesis. Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) negatively regulates this pathway by acting as a lipid phosphatase. Genetic alterations in the PIK3CA, AKT2 and PTEN gene are common in the PI3K/AKT pathway in human cancers and associated with the aggressiveness of the disease. Thus, drug discovery activities have been directed over the past few years to identify compounds that effectively and specifically disrupt this pathway in tumor cells. To appraise the possible contribution of genetic alterations in the PIK3CA, AKT2 and PTEN genes in activating PI3K/AKT pathway in areca-quid (AQ) associated oral cavity squamous cell carcinomas (OSCCs), PIK3CA mutations, PIK3CA and AKT2 amplifications, and inactivation of PTEN via loss of heterozygosity (LOH), homozygous deletion (HD) and promoter methylation were examined in 153 OSCCs. The frequency of PIK3CA mutations, PIK3CA and AKT2 amplifications, and inactivation of PTEN was 3.21%, 40.52%, 15.69% and 15.03%, respectively. Increased number of gene alterations in the PIK3CA, AKT2 and PTEN gene (χ2 trend test: P = 0.003 and P = 0.027, respectively) was positively associated with lymph node metastasis and tumor differentiation. Based on the status of gene alterations in the PIK3CA, AKT2 and PTEN gene, a gene dosage effect on disease-free and overall survival was observed in patients who had undergone radiotherapy after surgery; however, this gene dosage effect was not significant in patients who had been treated with surgery alone. In the subset of patients received radiotherapy after surgery, patients who had one alteration in PIK3CA/PTEN/AKT2 gene had a poorer disease-free and overall survival, as compared to those with normal PIK3CA/PTEN/AKT2; and those had at least 2 alterations in PIK3CA/PTEN/AKT2 gene would further worsen the condition. Our study provides a rational for exploring treatment strategies that include radiotherapy combined with compounds blocking PI3K/AKT pathway.

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 837.
Abstract 84: The L-ferritin receptor, Scara5, is expressed on breast cancer and glioma cells: A potential functional significance for cancer-associated high serum/CSF levels
Authors: Alkhateeb Ahmed , Webb Becky , Connor James
Published: February 2011

Elevated levels of circulating ferritin have been associated with several neoplasms, including neuroblastoma, glioblastoma, Hodgkin's lymphoma, and breast cancer. Despite the prognostic value of serum ferritin levels, its role in cancer biology is not understood. Ferritin has long been considered exclusively as an intracellular iron storage protein. However, several lines of evidence have suggested a role for ferritin beyond iron storage, such as angiogenesis, iron delivery, and modulation of the immune response. Recently, a receptor for L-ferritin (the predominant ferritin subunit in the serum and cerebrospinal fluid) has been identified as scavenger receptor class A, member 5 (Scara5). Our preliminary data show Scara5 to be expressed in glioma, neuroblastoma, and breast cancer cells. This novel observation led us to hypothesize that Scara5 internalizes L-ferritin, and serves as a non-transferrin iron delivery mechanism in cancer cells. In support of this hypothesis, we report here that both human liver and human heart ferritins increased cellular survival of the breast cancer cell line MCF-7 in serum free conditions. Taken together, these observations suggest an active functional role for circulating ferritin in tumor biology. The elevated levels of circulating ferritin observed in some cancers may enhance tumor metabolism and growth.

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 84.
Abstract 845: Vascular cell adhesion molecule-1 (VCAM-1) expression in patients with ovarian tumors of low malignant potential
Authors: Henretta Melissa , Scalici Jennifer M. , Duska Linda , Slack-Davis Jill , Atkins Kristen
Published: February 2011

The molecular basis for gynecologic tumor dissemination into the peritoneum is not well understood, however it is the primary mechanism of death in advanced stage ovarian cancers. Although serous borderline and serous invasive ovarian cancers are similar, they differ in their ability to implant and invade peritoneal structures. Vascular cell adhesion molecule-1 (VCAM-1), a cell surface receptor expressed on activated endothelial and mesothelial cells, regulates leukocyte attachment and extravasation at sites of inflammation. Recent studies by our group demonstrated the ability of ovarian carcinoma to induce the expression of VCAM-1 on mesothelial cells, and correlated the presence of VCAM-1 with peritoneal dissemination of the tumor. We undertook the current study to determine whether VCAM-1 is expressed on the mesothelium of patients with borderline ovarian tumors. After IRB approval was obtained, cell blocks containing peritoneum and omentum from 10 patients with borderline tumors were processed and stained using antibodies to VCAM-1. Mesothelial expression of VCAM-1 was determined by a single pathologist blinded to tumor type and stage. Samples were determined to be positive if mesothelial cells demonstrated membrane staining. Cytoplasmic staining for VCAM-1 was not considered positive, nor was staining of non-mesothelial cells. Of the 10 patients, four were stage 1a and six were stage 1c serous borderline tumors. Nine of 10 had peritoneal or omental biopsies that did not stain for VCAM-1. The one sample which did stain positively was micropapillary type, which is an invasive sub-type of borderline ovarian cancers. Together, these observations support the hypothesis that VCAM-1 expression correlates with ovarian cancer peritoneal invasion and offers a possible explanation for the inability of borderline tumors to invade peritoneal structures.

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 845.
Abstract 86: Role of autophagy in lymphoma treatment: Autophagy manipulation in lymphoma therapeutic cell killing
Authors: Gump Jacob M.
Published: February 2011

Manipulation of autophagy to augment cancer treatment is an area of active research. We sought to determine the role of autophagy in lymphoma treatment with cytotoxic chemotherapeutics alone and in combination with both genetic and pharmacologic manipulation (activation and inhibition) of autophagy. We found that cellular responses to certain chemotherapeutic agents are altered by autophagic manipulation whereas others are not. Using single cell microscopic assays and flow cytometry we have found that manipulation of autophagy has an effect on a subset of lymphoma cells in culture altering their response to cell death stimuli. The overall magnitude, kinetics and mechanistic aspects of apoptosis are altered in this subset of cells. This finding that there are differences in the response to autophagy manipulation between cancer cells in a population has implications for the treatment of lymphoma and other cancers.

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 86.
Abstract 871: Dermatofibrosarcoma protuberans in a black African population: A clinicopathologic study with emphasis on the predictors of recurrence and outcome
Authors: Ogun Gabriel O. , Ogunbiyi Adebola O.
Published: February 2011

Background: Dermatofibrosarcoma protuberans are relatively rare in our environment. Detailed studies on the subject in homogenous black African population are rare in literature. The aim of the study was to retrospectively analyze the clinical and histopathologic features of the tumor and identify the factors that directly influence recurrence, outcome and prognosis in the setting of a developing country with limited resources.

Materials and Methods: All cases of Dermatofibrosarcoma protuberans histopathologically diagnosed and available from the files and records of Department of Pathology, University College Hospital, Ibadan, Nigeria between January 1989 and December 2007 were identified, reviewed and included in the study. The detailed clinical parameters like age at presentation, gender, size and site of tumor, stage at presentation, treatment modalities, recurrence and follow up details; also details of histopathologic features like mitotic count and presence of tumor at the resection margins were analyzed.

Results: A total of 58 cases were identified and are presented. All the patients were Nigerians. Patient's age ranged from 5-74 years (median, 35years) with a modal age group of 30-39 years. The male/ female ratio had a male preponderance of 2.2:1. Tumor site distribution was trunk (39.5%), lower limb (27%), Upper limb (21%) and head and neck (12.5%). Tumor size ranged from 1.5 to 21cm. Seventy four percent presented with pT2 (TNM) stage tumor. Size of tumor larger than 7cm, mitotic count of greater than 7 per 10hpf and involvement of the subcutaneous tissue were strong indicators of the likelihood of recurrence. Forty five percent of our patients had recurrence with a patient having eight recurrences. The cost implications significantly delayed adjuvant therapy after surgical resection in our patients. This is because the cost of management is borne directly by patients in our environment. About 50% of our patients especially those with pT1 stage tumors were lost to follow up in less than 6 months. Two of our patients had features with fibrosarcoma-like transformation.

Conclusion: The trunk and the lower limb accounted for 66.5% of location of tumor. The follow up data was poor in patients with small sized tumors. Large tumor size and high mitotic count increased the rate of recurrence. The cost implication of care, which is directly borne by patients due to out-of pocket payment lead to poor follow up and 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 871.
Abstract 875: Ovarian and uterine carcinosarcoma: A comparative analysis of prognostic variables and survival outcomes
Authors: Garg Gunjal , Shah Jay P. , Bryant Christopher , Kumar Sanjeev , Morris Robert T.
Published: February 2011

Objective: Carcinosarcomas (malignant mixed mullerian tumor) of the female genital tract are rare tumors associated with poor outcome. Previous studies have demonstrated that even tumors of similar histology originating in organs that are in proximity may be biologically distinct entities by virtue of their occurrence through different molecular pathways. The objective of this study was to identify site specific differences in the clinical behavior and survival outcome of carcinosarcomas originating in female genital tract by comparing carcinosarcomas arising in the uterus and ovaries. Methods: Data on patients with uterine carcinosarcoma and ovarian carcinosarcoma were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and to identify possible predictors for survival. Results: The identified cohort included 3,683 women, with 2,759 (75%) uterine carcinosarcomas and 924 (25%) ovarian carcinosarcomas. Uterine carcinosarcoma patients were older than patients with ovarian carcinosarcoma (median age 67.61 vs. 65.83 years, p<0.001). Women with uterine carcinosarcomas compared with ovarian carcinosarcoma were more often African American (17.3% versus 6%; P<0.001) and presented more often with early stage disease (Stage I/II 56.6% compared with 24.6%; P <0.001). Uterine compared to ovarian carcinosarcomas differed significantly with regards to the performance of salpingo-oopherectomy (96 % versus 99.4 %; P = 0.001), lymphadenectomy (62.6% versus 41.2%; P <0.001), and administration of radiotherapy (38.2% versus 4.8%; P <0.001). No difference was found in survival between patients with uterine and ovarian carcinosarcoma on stage- stratified Kaplan- Meier survival analysis or multivariate analysis using Cox model. Although, age (p<0.001), race (p<0.001), marital status (p<0.001), stage (p<0.001), lymphadenectomy (p<0.001), and radiation (p=0.005) were all significant prognostic factors in uterine carcinosarcoma, only age (p=0.001), stage (p<0.001), and lymphadenectomy(p<0.001) reached statistical significance in ovarian carcinosarcoma on multivariate analysis. Conclusion: Ovarian carcinosarcomas present at a more advanced stage and have a comparable prognosis at each stage with uterine carcinosarcomas. Improved survival observed in lymphadenectomy group argues in favor of routinely performing lymph node dissection in patients with uterine and ovarian carcinosarcoma.

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 875.
Abstract 879: Mitochondrial DNA content and its association with lung cancer risk and clinical outcomes
Authors: Pu Xia , Lippman Scott M. , Gu Jian , Xing Jingliang , Chang Joe , Chang David , Spitz Margaret R. , Wu Xifeng
Published: February 2011

Mitochondrion is an essential cellular organelle generating energy, and also plays a key role in the initiation and regulation of apoptosis. Impaired mitochondria function may inhibit apoptosis; enhance reactive oxygen species and generate cancer related proteins. The difference in mitochondrial DNA (mtDNA) content (also termed mtDNA copy number) may contribute to cancer predisposition as well as variations in clinical outcomes. To test this hypothesis, we conducted a large-scale case-control study to investigate the role of mtDNA content in lung cancer etiology and clinical outcomes. MtDNA content in 2,442 newly diagnosed lung cancer patients and 2,417 matched controls were measured by quantitative real-time polymerase chain reaction. Clinical outcome data were collected for non-small cell lung cancer (NSCLC) patients (2,020 subjects). We analyzed the association of MtDNA copy number with the risk of developing lung cancer and also the clinical outcomes in NSCLC patients. MtDNA content was significantly lower in patients than controls (mean=1.17 vs. 1.23, P=4.28×10−4). Compared to higher mtDNA content (above the median value in the controls), lower mtDNA content was associated with a significantly increased risk for lung cancer (OR=1.25, 95%CI=1.11-1.41, P=1.52×10−4). In the trend analysis, we detected a significant dose-response relationship between mtDNA content and risk, as lower mtDNA content was associated with a progressively increased risk for lung cancer (P-trend=1.40×10−4). In the analysis of clinical outcomes, a significant difference in mtDNA content was observed between death and survival groups (mean=1.12 vs. 1.27, P=6.62×10−4) in early stage (stage I and II) NSCLC patients. Compared to those who have higher mtDNA content, patients who have lower mtDNA content had a 45% higher risk for death (HR=1.34, 95%CI=1.05-1.71, P=0.019), and a dramatically shorter survival time (58 months vs. 96 months, log-rank P=5.68×10−4). A dose-response effect of increased risk for death was found with decreased mtDNA content (P-trend=0.048) in this group of patients. No significant results were found in advance stage (stage III and IV) patients. To our knowledge, this is the first study to evaluate the association of MtDNA copy number with lung cancer risk and clinical outcomes. Our results suggested that lower mtDNA content is associated with increased lung cancer risk and poor prognosis in early stage NSCLC 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 879.
Abstract 884: Enhancing cultural communication to reduce cancer disparities
Authors: Quinn Gwendolyn P. , Chavez Julio Jimenez , Simmons Vani N. , Castro Eida , Gwede Clement K. , Vadaparampil Susan T. , Antonia Teresita M. , Meade Cathy , Brandon Thomas
Published: February 2011

An alliance between a patient's cultural identity and a physician's cultural competency can improve patient physician communication and ultimately reduce health disparities[1]. However, communication barriers in the patient-physician relationship contribute to health disparities in the cancer care setting.[2] Providers are often unaware of their skill level and perceptions and may believe they do not need improvement. 2 This study sought to develop and evaluate a brief intervention for oncology care providers to improve cultural communication related to Hispanic patients and families. Oncologists at a major cancer center were surveyed to identify which of the nine AHRQ cultural competency techniques they desired to receive more training (n= 72). 66% selected, “I am interested in receiving information on how to communicate difficult issues such as terminal illness and controversial diagnosis, in a way that is respectful to Hispanic culture.” A workshop was held for 55 staff containing a didactic lecture from an Hispanic provider addressing culture, terminal illness, and communication strategies. A panel of interpreters, translators, and bi-lingual providers answered questions from the audience and a group discussion was held. A seven item pre-test was administered prior to the workshop, followed by a three item post-test. 62% agreed the panel discussion was helpful in developing techniques for communicating bad news to Spanish speaking patients. At baseline 20% of participants felt very comfortable with their cultural communication skills, however, only 3% felt very comfortable after attending the intervention. At pre-test 25% reported having very little knowledge about the cultural context of breaking bad news to Hispanic patients, yet at post-test 0% reported having very little knowledge. These data suggest the training was successful overall, as well as aiding in identifying providers who previously had a high level of comfort based on misperceptions of good cultural communication and through the workshop realized they needed improvement.

[1] Brach, Cindy, Fraser, Irene

Can Cultural Competency Reduce Racial And Ethnic Health Disparities? A Review And Conceptual Model

Med Care Res Rev 2000 57: 181-217

[2] Saha, Somnath, Arbelaez, Jose J., Cooper, Lisa A.

Patient-Physician Relationships and Racial Disparities in the Quality of Health Care

Am J Public Health 2003 93: 1713-1719

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 884.
Abstract 885: GSTM1 CNV and promoter SNPs are associated with REC/SPT and survival after Retinoid Acid treatment for head and neck cancer
Authors: Zhang Xuemei , Huang Maosheng , Wu Xifeng , Kadlubar Susan , Yu Xinfeng , Caldwell David , Lin Jie , Ning Baitang , Kadlubar Fred F.
Published: February 2011

Purpose: This study sought to determine if copy number variant (CNV) combined with other genetic variants in the glutatione S-transferase Mu class1 (GSTM1) promoter have an important impact on recurrence and overall survival in head and neck cancer patients after retinoid acid treatment. Experimental Method: This study included 441 head and neck patients treated with retinoid acid. Among these cases, 133 experienced recurrence of disease and/or a second primary tumor, while 308 have single primary disease. TaqMan real-time PCR and direct sequencing were used to determine genetic variants in GSTM1. Recurrence and secondary primary tumor (REC/SPT) were evaluated by logistic regression modeling and overall survival was estimated by Kaplan-Meier analysis using STATA. Results: Regression analysis revealed significantly decreased REC/SPT and increased overall survival in subjects with at least 2 copies of GSTM1 (OR=0.57; 95%CI=0.35-0.95) but not in those with 1 copy of the gene. Kaplan-Meier survival analysis also revealed longer overall survival in patients with at least 2 copies of GSTM1. Allele frequency analysis showed −498 C>G, −426 A>G, −339 C>T polymorphisms were significantly associated with REC/SPT in head and neck cancer patients a(OR 0.12 (0.02-0.87), 0.30 (0.11-0.80) and 1.87 (1.00-3.51), respectively. Further survival analysis demonstrated that the −498G, −426G and −339C alleles significantly increased the overall survival in head and neck cancer subjects. Conclusion: These results suggest the GSTM1 CNV combined with single nucleotide polymorphisms is a better predictor of REC/SPT and overall survival of head and neck cancer after retinoic acid treatment than just measuring the presence/absence of GSTM1.

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 885.