title: EGFR expression in vulvar cancer: clinical implications and tumor heterogeneity.
abstract: Epidermal growth factor receptor (EGFR) protein expression was assessed by immunohistochemistry (IHC) in 150 cases of invasive vulvar squamous cell carcinoma. In addition, gene copy number status by fluorescence in situ hybridization was performed in a smaller set of samples. Results were correlated with patient's clinical data and prognostic factors. EGFR overexpression (2+ and 3+) was observed on the membrane in 24.66% and 21.33% of all cases, respectively. Higher EGFR expression was associated with depth of invasion (P = .0409) and disease recurrence (P = .0401). Cytoplasm staining was found in 21.33% of the cases and was associated with absence of nodal metastasis (P = .0061) and better survival (P = .0199). Intratumor heterogeneity of EGFR IHC staining was frequently observed (55.33%) and was associated with the presence of nodal metastasis (P = .0207) and tumor invasion (P = .0161). Worse survival outcomes have been demonstrated in tumors with EGFR heterogeneity (P = .0434). EGFR gene status evaluated by fluorescence in situ hybridization did not correlate with protein expression evaluated by IHC. In conclusion, EGFR cytoplasm staining has no link with poorer outcome; still, this pattern of staining is even more related to better prognosis. EGFR heterogeneity of staining correlated with more aggressive tumors, and presented to be an important marker of poor prognosis in vulvar squamous cell carcinoma. The usage of small biopsies or even tissue microarrays for vulvar cancer evaluation should be carefully reconsidered for the assessment of EGFR as the results may be misleading. Protein overexpression may be independent on gene amplification, showing that other molecular mechanisms than copy number variation may regulate protein expression of EGFR in vulvar cancer.
authors.affiliation: Molecular Morphology Department, AC Camargo Cancer Center, São Paulo 01508-010, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Melo Maia
authors.affiliation: Molecular Morphology Department, AC Camargo Cancer Center, São Paulo 01508-010, Brazil.
authors.forename: Adriana Mazega
authors.initials: AM
authors.lastname: Fontes
authors.affiliation: Molecular Morphology Department, AC Camargo Cancer Center, São Paulo 01508-010, Brazil.
authors.forename: André Mourão
authors.initials: AM
authors.lastname: Lavorato-Rocha
authors.affiliation: Molecular Morphology Department, AC Camargo Cancer Center, São Paulo 01508-010, Brazil.
authors.forename: Iara Sant'Ana
authors.initials: IS
authors.lastname: Rodrigues
authors.affiliation: Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo 01509-900, Brazil.
authors.forename: Louise
authors.initials: L
authors.lastname: de Brot
authors.affiliation: Gynecologic Oncology Department, AC Camargo Cancer Center, São Paulo 01509-900, Brazil.
authors.forename: Glauco
authors.initials: G
authors.lastname: Baiocchi
authors.affiliation: Pathology Department, Fleury Institute, São Paulo 04344-903, Brazil.
authors.forename: Monica Maria
authors.initials: MM
authors.lastname: Stiepcich
authors.affiliation: Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo 01509-900, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Molecular Morphology Department, AC Camargo Cancer Center, São Paulo 01508-010, Brazil. Electronic address: rafael.malagoli@gmail.com.
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056915:DNA Copy Number Variations; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D011379:Prognosis; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D066246:ErbB Receptors
keywords: EGFR; FISH; Immunohistochemistry; Prognosis; Vulvar carcinoma