Intratumoral heterogeneity of HER2 protein and amplification of HER2 gene in salivary duct carcinoma

Pathol Int. 2014 Sep;64(9):453-9. doi: 10.1111/pin.12195. Epub 2014 Sep 10.

Abstract

Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands, and accounts for 1-3% of all malignant salivary gland tumors, resembling morphologically invasive ductal carcinoma (IDC) of the breast. In contrast to IDC of the breast and gastric carcinoma (GC), the study of human epidermal growth factor receptor 2 (HER2) in SDC has not progressed. Therefore, we investigated the relationship between HER2 protein expression and amplification of the HER2 gene, and compared them in terms of intratumoral heterogeneity (ITH) in 13 cases of SDC using immunohistochemistry and dual color in situ hybridization. We found seven cases with protein overexpression (53.8%) and five cases with gene amplification (38.5%) in accordance with ASCO/CAP guidelines. ITH of HER2 protein expression was seen in seven cases (53.8%). Interestingly, the ratio of the HER2 gene showed homogenous distribution with or without the presence of ITH of HER2 protein expression. SDC tends to have more ITH of HER2 protein similarly to GC, in contrast to IDC of the breast. ITH of HER2 protein in SDC has no heterogeneity of the HER2 gene amplification. The mechanism of HER2 protein expression in SDC might proceed through a more complex pathway relative to that of IDC of the breast.

Keywords: heterogeneity; human epidermal growth factor receptor 2 (HER2); salivary duct carcinoma (SDC).

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Child
  • Child, Preschool
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic*
  • Genetic Heterogeneity
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization / methods
  • Male
  • Middle Aged
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / metabolism*
  • Salivary Gland Neoplasms / pathology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Receptor, ErbB-2