Adenocarcinomas of the biliary tract and gallbladder are aggressive tumors with a poor prognosis. Standard chemotherapy often offers minimal benefit. Because epidermal growth factor receptor and HER-2/neu antagonists have been successfully used in adenocarcinomas from other sites, their use in cholangiocarcinoma can be potentially beneficial. This study examines the epidermal growth factor receptor and HER-2/neu expression and the epidermal growth factor receptor gene copy number in biliary tract adenocarcinomas. Fifty-one formalin-fixed, paraffin-embedded cases of adenocarcinomas (26 intrahepatic, 19 extrahepatic, 6 gallbladder) were stained with monoclonal antibodies against epidermal growth factor receptor and HER-2/neu. Fluorescence in situ hybridization analysis was performed in 37 cases using probes directed against epidermal growth factor receptor and centromeric region of chromosome 7. Epidermal growth factor receptor expression was present in 41 (80%) cases, with moderate or strong epidermal growth factor receptor staining in 30 (59%) cases. HER-2/neu was positive in 2 (4%) cases. Fluorescence in situ hybridization analysis showed gain in epidermal growth factor receptor gene copy number in 17 (46%) tumors. Of the latter, 1 showed gene amplification, whereas all others showed gain in chromosome 7, indicating balanced polysomy. Epidermal growth factor receptor overexpression by immunohistochemistry correlated significantly with epidermal growth factor receptor copy number by fluorescence in situ hybridization (P = .02). HER2/neu expression is uncommon in these tumors.
"The goal of this study was to assess a large series of intrahepatic, perihilar and extrahepatic cholangiocarcinomas for FGFR2 translocations and clinicopathologic correlates using a fluorescence in situ hybridization (FISH) assay that could be routinely performed in a clinical laboratory. We also undertook investigation of these tumors for ROS1 translocations and ERBB2 (HER2) amplification since the tyrosine kinases encoded by these genes have also been reported in cholangiocarcinoma   "
[Show abstract][Hide abstract] ABSTRACT: Patients with cholangiocarcinoma often present with locally advanced or metastatic disease. There is a need for effective therapeutic strategies for advanced stage cholangiocarcinoma. Recently, FGFR2 translocations have been identified as a potential target for tyrosine kinase inhibitor therapies. This study evaluated 152 cholangiocarcinomas and 4 intraductal papillary biliary neoplasms of the bile duct for presence of FGFR2 translocations by fluorescence in situ hybridization (FISH) and characterized the clinicopathologic features of cases with FGFR2 translocations. Thirteen (10 women, 3 men; 8%) of 156 biliary tumors harbored FGFR2 translocations, including 12 intrahepatic cholangiocarcinomas (12/96; 13%) and 1 intraductal papillary neoplasm of the bile duct. Histologically, cholangiocarcinomas with FGFR2 translocations displayed prominent intraductal growth (62%) or anastomosing tubular glands with desmoplasia (38%). Immunohistochemically, the tumors with FGFR2 translocations frequently showed weak and patchy expression of CK19 (77%). Markers of the stem cell phenotype in cholangiocarcinoma, HepPar1 and CK20, were negative in all cases. The median cancer-specific survival for patients whose tumors harbored FGFR2 translocations was 123 months compared to 37 months for cases without FGFR2 translocations (p = 0.039). This study also assessed 100 cholangiocarcinomas for ERBB2 amplification and ROS1 translocations. Of the cases tested, 3% and 1% were positive for ERBB2 amplification and ROS1 translocation, respectively. These results confirm that FGFR2, ERRB2, and ROS1 alterations are potential therapeutic targets for intrahepatic cholangiocarcinoma.
Human pathology 08/2014; 45(8). DOI:10.1016/j.humpath.2014.03.014 · 2.77 Impact Factor
"Over expression of EGF correlated significantly with copy number of EGF. HER2/neu expression is uncommon in these tumors. "
[Show abstract][Hide abstract] ABSTRACT: Gallbladder cancer (GBC) is a common malignancy of the biliary tract and involves the changes in multiple oncogenes and multiple genetic genes. Since over the past decade there has been an advance in the knowledge of the genetic basis of cancer, mainly as a result of the rapid progression of molecular technology; however, conventional therapeutic approaches have not had much impact on the course of this aggressive neoplasm. Knowledge of the molecular biology of GBC is rapidly growing. Genetic alterations in GBC include adenosine triphosphate-binding cassette transporter ABCG8, membrane-bound enzyme ADAM-17 of multi-functional gene family, and other genes including p53, COX2, XPC, and RASSF1A. The advances in molecular biology have potential implications for the detection of this disease, using Synuclein-gamma, Syndecan-1, glycoprotein 72 (TAG-72), tumor endothelial marker 8 protein (TEM8) and TNF-alpha. The use of these molecular diagnostic methods is of clinical importance for the gene replacement therapy, genetic prodrug activation therapy, and antisense immunology technology for the treatment of malignancy. The author reviewed recent publications on PubMed, and summarized molecular biology of GBC, with an emphasis on features of potential clinical implications for diagnosis and management.
North American Journal of Medical Sciences 10/2012; 4(10):435-41. DOI:10.4103/1947-2714.101979
"A better understanding of the chromosome 17 abnormalities will help to select patients who may respond well to some therapies. The examination of HER2 expression and copy number amplification (17q21.1) is widely utilized for predicting therapeutic response for trastuzumab (Herceptin) not only in breast cancer, but also in malignancies of the gastrointestinal tract [2–5]. "
[Show abstract][Hide abstract] ABSTRACT: Abnormalities of chromosome 17 are important molecular genetic events in human breast cancers. Several famous oncogenes (HER2, TOP2A and TAU), tumor suppressor genes (p53, BRCA1 and HIC-1) or DNA double-strand break repair gene (RDM1) are located on chromosome 17. We searched the literature on HER2, TOP2A, TAU, RDM1, p53, BRCA1 and HIC-1 on the Pubmed database. The association of genes with chromosome 17, biological functions and potential significance are reviewed. In breast cancer, the polysomy 17 (three or more) is the predominant numerical aberration. HER2 amplification is widely utilized as molecular markers for trastuzumab target treatment. Amplified TOP2A, TAU and RDM1 genes are related to a significant response to anthracycline-based chemotherapy, taxane or cisplatin, respectively. In contrast, p53, BRCA1 and HIC-1 are important tumor suppressor genes related to breast carcinogenesis. This review focused on several crucial molecular markers residing on chromosome 17. The authors consider the somatic aberrations of chromosome 17 and associated genes in breast cancer.
International Journal of Molecular Sciences 12/2011; 12(9):5672-83. DOI:10.3390/ijms12095672 · 2.86 Impact Factor
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