PMID- 27864120 OWN - NLM STAT- MEDLINE DCOM- 20170828 LR - 20181202 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 61 DP - 2017 Mar TI - Epidermal growth factor receptor as an adverse survival predictor in squamous cell carcinoma of the penis. PG - 97-104 LID - S0046-8177(16)30310-0 [pii] LID - 10.1016/j.humpath.2016.07.041 [doi] AB - 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-type and 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Silva Amancio, Alice Muglia Thomaz da AU - Silva Amancio AM AD - Department of Anatomic Pathology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Cunha, Isabela Werneck da AU - Cunha IW AD - Department of Anatomic Pathology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Neves, Jose Ivanildo AU - Neves JI AD - Department of Anatomic Pathology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Quetz, Josiane da Silva AU - Quetz JD AD - Department of Pathology, Cancer Institute of Ceara, 60351-010, Fortaleza, CE, Brazil. FAU - Carraro, Dirce Maria AU - Carraro DM AD - Department of Anatomic Pathology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Rocha, Rafael Malagoli AU - Rocha RM AD - Department of Anatomic Pathology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Zequi, Stenio Cassio AU - Zequi SC AD - Urology Division, Department of Pelvic Surgical Oncology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Cubilla, Antonio Leopoldo AU - Cubilla AL AD - Instituto de Patologia e Investigacion, Universidad Nacional de Asuncion, 1617, Asuncion, Paraguay. FAU - da Fonseca, Francisco Paulo AU - da Fonseca FP AD - Urology Division, Department of Pelvic Surgical Oncology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Lopes, Ademar AU - Lopes A AD - Urology Division, Department of Pelvic Surgical Oncology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Cunha, Maria do Perpetuo Socorro Saldanha da AU - Cunha MD AD - Department of Pathology, Cancer Institute of Ceara, 60351-010, Fortaleza, CE, Brazil. FAU - Lima, Marcos Venicio Alves AU - Lima MV AD - Department of Urology, Cancer Institute of Ceara, 60351-010, Fortaleza, CE, Brazil. FAU - Vassallo, Jose AU - Vassallo J AD - Department of Anatomic Pathology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil; Laboratory of Molecular and Investigative Pathology, Faculty of Medical Sciences, State University of Campinas Medical School, 13083-970, Campinas, SP, Brazil. FAU - Guimaraes, Gustavo Cardoso AU - Guimaraes GC AD - Urology Division, Department of Pelvic Surgical Oncology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil. FAU - Soares, Fernando Augusto AU - Soares FA AD - Department of Anatomic Pathology, A.C. Camargo Cancer Center, 01508-010, Sao Paulo, SP, Brazil; General Pathology, Faculty of Dentistry, University of Sao Paulo, 05508-000, Sao Paulo, SP, Brazil. Electronic address: fasoares@cipe.accamargo.org.br. LA - eng PT - Journal Article DEP - 20161115 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*analysis/genetics MH - Biopsy MH - Carcinoma, Squamous Cell/*chemistry/genetics/mortality/pathology MH - Chromosomes, Human, Pair 7 MH - DNA Copy Number Variations MH - DNA Mutational Analysis MH - ErbB Receptors/*analysis/genetics MH - Gene Amplification MH - Gene Dosage MH - Genetic Predisposition to Disease MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Mutation MH - Neoplasm Invasiveness MH - Neoplasm Recurrence, Local MH - Penile Neoplasms/*chemistry/genetics/mortality/pathology MH - Phenotype MH - Predictive Value of Tests MH - Proportional Hazards Models MH - Risk Factors MH - Young Adult OTO - NOTNLM OT - EGFR OT - FISH OT - Immunohistochemistry OT - Penile cancer OT - Prognosis EDAT- 2016/11/20 06:00 MHDA- 2017/08/29 06:00 CRDT- 2016/11/20 06:00 PHST- 2016/03/02 00:00 [received] PHST- 2016/07/07 00:00 [revised] PHST- 2016/07/15 00:00 [accepted] PHST- 2016/11/20 06:00 [pubmed] PHST- 2017/08/29 06:00 [medline] PHST- 2016/11/20 06:00 [entrez] AID - S0046-8177(16)30310-0 [pii] AID - 10.1016/j.humpath.2016.07.041 [doi] PST - ppublish SO - Hum Pathol. 2017 Mar;61:97-104. doi: 10.1016/j.humpath.2016.07.041. Epub 2016 Nov 15.