Decreased survival in EGFR gene amplified vulvar carcinoma

作者: Whitfield B. Growdon , Susan L. Boisvert , Sara Akhavanfard , Esther Oliva , Dora C. Dias-Santagata

DOI: 10.1016/J.YGYNO.2008.07.038

关键词: Gene duplicationVulvar Squamous Cell CarcinomaFluorescence in situ hybridizationEGFR Gene AmplificationVulvar cancerGene mutationCancer researchVulvar CarcinomaMedicinePolysomy

摘要: Objective. We undertook an extensive molecular characterization of the epidermal growth factor receptor (EGFR) gene in vulvar squamous cell carcinomas to investigate EGFR mutation and/or genomic amplification and its association with protein expression, high-risk human papillomavirus (HPV) status clinical outcome. Methods. A cohort 51 cancer patients distributed across all FIGO stages was selected for immunohistochemistry (IHC) fluorescence situ hybridization. expression were correlated HPV status, mutational prognostic variables. Fisher's exact tests, Kaplan–Meier survival estimates a Cox proportional-hazards model utilized. Results. chromosome 7 high polysomy observed 12% 6% cases, respectively. IHC malignant tissue 3+ staining demonstrated 100% sensitivity 79% specificity detect amplification, yielding 39% positive predictive value. Decreased (pb0.025) associated more statistically robust 3.3 hazard ratio (pb0.005) that controlled age at diagnosis, stage lymph node metastasis. Univariate analysis confirmed absence (pb0.001). Common activating mutations not identified. Conclusion. subset carcinoma identified HPV-independent poor prognosis. Given response targeted therapy other tumor types, these may be candidates therapeutic strategies target pathway.

参考文章(49)
David Whitcombe, Jane Theaker, Simon P. Guy, Tom Brown, Steve Little, Detection of PCR products using self-probing amplicons and fluorescence. Nature Biotechnology. ,vol. 17, pp. 804- 807 ,(1999) , 10.1038/11751
Akihiko Iwasawa, Pekka Nieminen, Matti Lehtinen, Jorma Paavonen, Human papillomavirus in squamous cell carcinoma of the vulva by polymerase chain reaction Obstetrics & Gynecology. ,vol. 89, pp. 81- 84 ,(1997) , 10.1016/S0029-7844(96)00376-6
M Ranson, Epidermal growth factor receptor tyrosine kinase inhibitors British Journal of Cancer. ,vol. 90, pp. 2250- 2255 ,(2004) , 10.1038/SJ.BJC.6601873
Bobbie C Sutton, Richard A Allen, William E Moore, S Terence Dunn, Distribution of human papillomavirus genotypes in invasive squamous carcinoma of the vulva. Modern Pathology. ,vol. 21, pp. 345- 354 ,(2008) , 10.1038/MODPATHOL.3801010
A.M. Stroup, L.C. Harlan, E.L. Trimble, Demographic, clinical, and treatment trends among women diagnosed with vulvar cancer in the United States. Gynecologic Oncology. ,vol. 108, pp. 577- 583 ,(2008) , 10.1016/J.YGYNO.2007.11.011
Yoon Kyung Jeon, Sook-Whan Sung, Jin-Haeng Chung, Weon-Seo Park, Jeong-Wook Seo, Chul Woo Kim, Doo Hyun Chung, Clinicopathologic features and prognostic implications of epidermal growth factor receptor (EGFR) gene copy number and protein expression in non-small cell lung cancer Lung Cancer. ,vol. 54, pp. 387- 398 ,(2006) , 10.1016/J.LUNGCAN.2006.08.015
Jeffrey J. Raizer, HER1/EGFR tyrosine kinase inhibitors for the treatment of glioblastoma multiforme Journal of Neuro-oncology. ,vol. 74, pp. 77- 86 ,(2005) , 10.1007/S11060-005-0603-7
Joaquín Arribas, José Baselga, Who will benefit from treatment against EGFR Lancet Oncology. ,vol. 6, pp. 257- 258 ,(2005) , 10.1016/S1470-2045(05)70142-X
Will R. Voelzke, W. Jeffery Petty, Glenn J. Lesser, Targeting the epidermal growth factor receptor in high-grade astrocytomas. Current Treatment Options in Oncology. ,vol. 9, pp. 23- 31 ,(2008) , 10.1007/S11864-008-0053-5
Niklas Reimers, Hans U. Kasper, Soenke J. Weissenborn, Hartmut Stützer, Simon F. Preuss, Thomas K. Hoffmann, Ernst Jan M. Speel, Hans P. Dienes, Herbert J. Pfister, Orlando Guntinas-Lichius, Jens P. Klussmann, Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer International Journal of Cancer. ,vol. 120, pp. 1731- 1738 ,(2007) , 10.1002/IJC.22355