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

Wim Van Boxtel,Marianne A Jonker,Maike J.M Uijen,Carla M.L Van Herpen,Gerald W Verhaegh,Jack A Schalken,Stefan M Willems,Ilse C.H Van Engen-Van Grunsven

doi:10.1016/j.oraloncology.2020.105018

Abstract

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

Highlights

Salivary duct carcinoma (SDC) is an aggressive subtype of salivary gland cancer (SGC) with a median overall survival (OS) of 3–5 years after primary diagnosis [1,2,3,4]
We previously showed that the absolute number of tumor-positive lymph nodes in the neck dissection is a prognostic factor in a multivariable Cox regression analysis [1]
We evaluated whether expression of c-MET, E-cadherin, and tumor or neovascular Prostate-specific membrane antigen (PSMA) expression are prognostic factors for SDC using Kaplan-Meier survival curves, univariable and multivariable Cox regression analyses

Summary

Introduction

Salivary duct carcinoma (SDC) is an aggressive subtype of salivary gland cancer (SGC) with a median overall survival (OS) of 3–5 years after primary diagnosis [1,2,3,4]. Primary treatment of SDC consists of tumor resection, most often in combination with a neck dissection and postoperative radiotherapy. Despite this extensive primary treatment, the recurrence risk is high with a 3-year disease-free survival of only. Better knowledge of prognostic factors is needed to increase our understanding of the pathogenesis of SDC and to guide treatment decisions. Androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression are key tumor characteristics of SDC, but these are no prognostic factors [1]. All SDCs are AR-positive (96% in our cohort after expert pathology review) [1], and androgen

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