Increased ERBB2 Gene Copy Numbers Reveal a Subset of Salivary Duct Carcinomas with High Densities of Tumor Infiltrating Lymphocytes and PD-L1 Expression

Kyriakos Chatzopoulos, Andrea R. Collins, Sotiris Sotiriou, Michael G. Keeney, Daniel W. Visscher, Michael Rivera, David J. Schembri-Wismayer, Jean E. Lewis, Patricia T. Greipp, William R. Sukov, Ashish V. Chintakuntlawar, Katharine A. Price, Joaquin J. Garcia

Research output: Contribution to journalArticle

Abstract

Salivary duct carcinoma (SDC) commonly expresses androgen receptor (AR) and HER2, giving rise to treatment implications. SDC may also express programmed-death-ligand-1 (PD-L1), a predictive marker of response to checkpoint inhibitors. PD-L1 can be associated with genomic instability and high density of tumor infiltrating lymphocytes (TILs). Evaluation of HER2 immunohistochemistry (IHC) in SDC is not standardized, and relationships between ERBB2 copy numbers, PD-L1 expression and TILs in SDC are unknown. We evaluated 32 SDCs for HER2, AR and PD-L1 expression (IHC), ERBB2 status (FISH) and TILs (slide review). HER2 was scored with three different systems (breast, gastric, proposed salivary gland). PD-L1 was evaluated with the combined positive score. Most patients were older men, presenting at advanced clinical stage with nodal or distant metastases. During follow-up (mean 5 years, range 6 months to 21 years), 25 of the 32 patients (78%) died of SDC. We propose a HER2 IHC scoring system which accurately predicts underlying ERBB2 amplification or increased copy numbers in SDC. Most tumors had increased ERBB2 copy numbers (19/32 amplification, 6/32 aneusomy), a finding associated with higher TIL densities (p = 0.045) and PD-L1 expression (p = 0.025). Patients with TILs ≥ 40% had better prognoses (Log-Rank p = 0.013), with TILs being favorable prognosticators in univariate analysis (Hazard ratio: 0.18, p = 0.024). A subset of SDCs with increased ERBB2 copy numbers have higher TILs and PD-L1 expression. TILs ≥ 40% are associated with better prognosis.

Original languageEnglish (US)
JournalHead and Neck Pathology
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • FISH
  • HER2 immunohistochemistry
  • PD-L1
  • Salivary duct carcinoma
  • Tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Otorhinolaryngology
  • Oncology

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    Chatzopoulos, K., Collins, A. R., Sotiriou, S., Keeney, M. G., Visscher, D. W., Rivera, M., Schembri-Wismayer, D. J., Lewis, J. E., Greipp, P. T., Sukov, W. R., Chintakuntlawar, A. V., Price, K. A., & Garcia, J. J. (Accepted/In press). Increased ERBB2 Gene Copy Numbers Reveal a Subset of Salivary Duct Carcinomas with High Densities of Tumor Infiltrating Lymphocytes and PD-L1 Expression. Head and Neck Pathology. https://doi.org/10.1007/s12105-020-01163-x