Decreased survival in EGFR gene amplified vulvar carcinoma

Abstract 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 EGFR protein expression, high-risk human papillomavirus (H...

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Published in:Gynecologic oncology 2008-11, Vol.111 (2), p.289-297
Main Authors: Growdon, Whitfield B, Boisvert, Susan L, Akhavanfard, Sara, Oliva, Esther, Dias-Santagata, Dora C, Kojiro, Sakiko, Horowitz, Neil S, Iafrate, A. John, Borger, Darrell R, Rueda, Bo R
Format: Article
Language:English
Subjects:
Aged
Amplification
Carcinoma in Situ - enzymology
Carcinoma in Situ - genetics
Carcinoma in Situ - pathology
Carcinoma in Situ - virology
Carcinoma, Squamous Cell - enzymology
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - pathology
Carcinoma, Squamous Cell - virology
Cohort Studies
DNA Mutational Analysis
Epidermal growth factor receptor
Female
Gene Amplification
Genes, erbB-1
Hematology, Oncology and Palliative Medicine
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Neoplasm Staging
Obstetrics and Gynecology
Papillomaviridae - classification
Papillomavirus Infections - genetics
Papillomavirus Infections - pathology
Papillomavirus Infections - virology
Proportional Hazards Models
Receptor, Epidermal Growth Factor - biosynthesis
Receptor, Epidermal Growth Factor - genetics
Retrospective Studies
Squamous cell carcinoma
Vulvar cancer
Vulvar Neoplasms - enzymology
Vulvar Neoplasms - genetics
Vulvar Neoplasms - pathology
Vulvar Neoplasms - virology
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Summary:Abstract 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 EGFR protein expression, high-risk human papillomavirus (HPV) status and clinical outcome. Methods A cohort of 51 vulvar cancer patients distributed across all FIGO stages was selected for immunohistochemistry (IHC) and fluorescence in situ hybridization. EGFR expression and gene amplification were correlated with high-risk HPV status, EGFR mutational status and clinical prognostic variables. Fisher's exact tests, Kaplan–Meier survival estimates and a Cox proportional-hazards model were utilized. Results EGFR gene amplification and chromosome 7 high polysomy were observed in 12% and 6% of cases, respectively. IHC of malignant tissue with 3+ staining demonstrated 100% sensitivity and 79% specificity to detect EGFR gene amplification, yielding a 39% positive predictive value. Decreased survival ( p < 0.025) was observed in patients with gene amplification, and was associated with a more statistically robust 3.3 hazard ratio ( p < 0.005) in the Cox proportional-hazards model that controlled for age at diagnosis, stage and lymph node metastasis. Univariate analysis confirmed that EGFR gene amplification was associated with the absence of high-risk HPV ( p < 0.001). Common activating EGFR gene mutations were not identified. Conclusion A subset of patients with vulvar squamous cell carcinoma was identified with EGFR gene amplification that was HPV-independent and associated with poor prognosis. Given the association of EGFR amplification with response to targeted therapy in other tumor types, these patients may be candidates for therapeutic strategies that target the EGFR pathway.
ISSN:0090-8258
1095-6859
DOI:10.1016/j.ygyno.2008.07.038