Prognostic value of PSMA, c-MET and E-cadherin in salivary duct carcinoma

Oral Oncol. 2020 Nov:110:105018. doi: 10.1016/j.oraloncology.2020.105018. Epub 2020 Oct 8.

Abstract

Objectives: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29-46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic factors in SDC.

Materials and methods: Expression levels of these proteins were established on tissue microarrays containing 165 primary SDC tumor specimens. Association with survival was studied with Kaplan-Meier curves, and univariable and multivariable Cox regression models. Furthermore, association with lymph node status, AR and HER2 expression, and gender was studied.

Results: We found that patients with high PSMA tumor expression showed a significantly longer overall survival (OS) (median 83 vs. 43 months, P = 0.022), a trend towards a longer DFS (median 51 vs. 22 months, P = 0.094), and significantly reduced hazard ratio for death in the univariable Cox regression model (HR 0.46, P = 0.034). In the multivariable model only a high number of tumor-positive lymph nodes and high age (>80) at diagnosis were prognostic for poor OS. High PSMA tumor expression was also significantly associated with low N-stage (P = 0.001) and expression was higher in women versus men (P = 0.029). High PSMA tumor expression and E-cadherin loss were significantly associated with strong and weak AR-expression, respectively (P = 0.033 and P = 0.007). None of the factors were significantly associated with HER2 expression.

Conclusion: c-MET, E-cadherin, and tumor and neovascular PSMA expression are no independent prognostic factors in SDC.

Keywords: Cadherins; E-cadherin; Genes, erbB-2; HER-2; PSMA; Prognosis; Proto-Oncogene Proteins c-met; Receptors, Androgen; Salivary Gland Neoplasms; Survival analysis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Carcinoma, Ductal / diagnosis
  • Carcinoma, Ductal / etiology*
  • Carcinoma, Ductal / mortality
  • Carcinoma, Ductal / therapy
  • Disease Susceptibility
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Proteasome Endopeptidase Complex / metabolism*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Salivary Gland Neoplasms / diagnosis
  • Salivary Gland Neoplasms / etiology*
  • Salivary Gland Neoplasms / mortality
  • Salivary Gland Neoplasms / therapy

Substances

  • AR protein, human
  • Biomarkers, Tumor
  • Cadherins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Receptors, Androgen
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Proteasome Endopeptidase Complex