Epidermal growth factor receptor as an adverse survival predictor in squamous cell carcinoma of the penis

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Thomaz da Silva Amancio, Alice Muglia ; da Cunha, Isabela Werneck ; Neves, Jose Ivanildo ; Quetz, Josiane da Silva ; Carraro, Dirce Maria ; Rocha, Rafael Malagoli ; Zequi, Stenio Cassio ; Cubilla, Antonio Leopoldo ; da Fonseca, Francisco Paulo ; Lopes, Ademar ; Socorro Saldanha da Cunha, Maria do Perpetuo ; Alves Lima, Marcos Venicio ; Vassallo, Jose ; Guimaraes, Gustavo Cardoso ; Soares, Fernando Augusto

• Document type: Journal article
• Source: HUMAN PATHOLOGY; v. 61, p. 97-104, MAR 2017.
• Web of Science Citations: 4

Abstract

Penile carcinoma (PC) is more frequent in underdeveloped countries, generally is diagnosed at an advanced stage when therapeutic options are restricted, and thus is associated with high morbidity/mortality rates. Recent studies have demonstrated clinical benefits with epidermal growth factor receptor (EGFR) targeted therapy in patients with PC, although there is no test that provides accurate patient selection. The aim of the present study was to evaluate the prognostic value of EGFR gene and protein status in tumor samples from patients with primary penile squamous cell carcinoma. We assessed the expression of wild type and 2 mutant EGFR isoforms (delA746-E750 and mL858R) by immunohistochemistry in 139 samples, of which 49 were also evaluated for EGFR copy number by fluorescence in situ hybridization (FISH). Positive immunohistochemical staining of wild-typeand mutant EGFR was evidenced by complete and strong membranous staining. For FISH analysis, cases were considered unaltered, polysomic, or amplified, as determined by signals of the EGFR gene and chromosome 7. An independent cohort of 107 PC samples was evaluated for mutations in EGFR, KRAS, and BRAF. Protein overexpression was noted in nearly half of the cases and was associated with cancer recurrence (P =.004) and perineural invasion (P =.005). Expression of the 2 mutated EGFR isoforms was not observed. The FISH status was not associated with protein expression. Altered FISH (polysomy and gene amplification) was an independent risk factor for dying of cancer. Only 1 patient of 107 presented KRAS mutations, and no mutations of EGFR or BRAF were observed. (C) 2017 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 09/52088-3 - Cancer of the penis, a real Brazilian problem: from morphology to molecular etiopathogenesis
• Grantee: José Vassallo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/09845-0 - The role of epidermal growth factor receptors family in the prognosis of penile carcinoma patients
• Grantee: Alice Muglia Thomaz da Silva Amancio
• Support Opportunities: Scholarships in Brazil - Doctorate