title: EGFR and cyclin D1 in nodular melanoma: correlation with pathohistological parameters and overall survival.
abstract: Considering that nodular melanoma (NM) has the potential to show an early distant metastasis, there is an urgent need for the discovery and evaluation of new diagnostic and prognostic biomarkers. We aimed to investigate the protein expression of membrane and nuclear epidermal growth factor receptor (EGFR), cyclin D1, and the corresponding gene status in NM samples and correlate the results obtained with clinicopathological parameters and overall survival of patients. Immunohistochemical and fluorescence in-situ hybridization analyses were carried out on tissue microarrays constructed from 110 NM samples, 30 compound nevi, and 38 dysplastic nevi. NM samples showed 24% strong cyclin D1 and 37% strong Ki67 protein expression compared with 3 and 0% strong cyclin D1 and Ki67 expression in the control group. Membrane EGFR expression was detected in 50% of NM cases, whereas EGFR gene amplification was detected in only 4% of NM cases. Multiple NM samples presented simultaneous membrane and nuclear EGFR expression. We found a negative correlation between tumor thickness and membrane EGFR expression. It was also observed that membrane EGFR 3+ NM samples presented ulceration significantly more often than membrane EGFR-negative (0) NM samples. In univariate analysis, carried out on 44 patients with follow-up data, both nuclear and membrane EGFR overexpression showed a correlation with a shorter overall survival. Nuclear EGFR (++, +++) showed 3.06 and membrane EGFR (2+, 3+) showed 2.76 higher risk of mortality compared with patients with low and negative nuclear and membrane EGFR expression (P<0.05).
authors.affiliation: aDepartment of Pathology, Faculty of Medicine, University of Rijeka bDepartment of Surgery, Clinical Hospital Centre Rijeka cDepartment of Oncology and Radiotherapy, Clinical Hospital Centre Rijeka, Rijeka, Croatia.
authors.forename: Miljenko
authors.initials: M
authors.lastname: Katunarić
authors.forename: Davor
authors.initials: D
authors.lastname: Jurišić
authors.forename: Marija
authors.initials: M
authors.lastname: Petković
authors.forename: Maja
authors.initials: M
authors.lastname: Grahovac
authors.forename: Blaženka
authors.initials: B
authors.lastname: Grahovac
authors.forename: Gordana
authors.initials: G
authors.lastname: Zamolo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000401:mortality* / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors