Features of the expression of prognostic markers p16, Her2 / new and changes in the corresponding genes in individual phenotypes of cancers of unknown primary origin.

Abstract

Background. Approximately 2/3 of cancers of unknown primary origin (CUP) are adenocarcinomas with mucin production, the formation of gland-like structures and immunohistochemistry results that can determine the histological subtype, but cannot determine the exact primary place of origin. The remaining 1/3 of CUP is a mixture of non-adenocarcinomas, including squamous cell carcinomas, neuroendocrine carcinomas, small-cell and large-cell undifferentiated carcinomas. Objective. In such cases, molecular profile identification and gene sequencing may be a promising approach to the classification and direct treatment of CUP. Methods. A retrospective analysis of biopsy or postoperative material of 61 patients (34 women and 27 men) aged 26 to 74 years (mean 53.4 ± 11.42; median 52) with an initial diagnosis of CUP was performed. Immunohistochemical studies were carried out according to the protocols of TermoScientific (USA) with antibodies to p16INK4a and HER2/neu. Fluorescence in situ hybridization was performed according to the protocol of ZytoVision GmbH (Germany). Changes in the ERBB2 and CDKN2A genes were evaluated for gene amplification and deletion of the 9p21 locus, respectively, with double-labeled DNA probes. Results. Of the 61 studied cases of CUP, p16 expression was positive in 31 cases (51%), the basis for which was 9 homozygous and 19 heterozygous 9p21 deletions, which were found in all but one of the studied CUP phenotypes. HER2 / neu expression was positive (2 + / 3 +) in 15 of 61 (25%) CUP, but only in 9 of them had actual amplification of the ERBB2 gene on FISH in 5 phenotypes. Conclusion . The reduced number of phenotypes with amplification of the ERBB2 gene makes it more specific for the differential diagnosis of CUP, compared with the deletion of 9p21 (p16 / CDKN2A), which is likely to be universal in acquiring an aggressive course of carcinomas of various localizations.