Biomarker immunoprofile in salivary duct carcinomas: clinicopathological and prognostic implications with evaluation of the revised classification

Abstract

Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise de novo or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence in situ hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than de novo SDCs (P = 0.015, < 0.001, 0.045, and 0.02, respectively). In multivariate analysis, AR− and CK5/6+ were associated with shorter progression-free survival (P = 0.027 and 0.004, respectively). Moreover, patients with p53-extreme negative/positive demonstrated poorer overall survival (P = 0.007). On assessing the revised classification by the combination of biomarker expression, the percentages of each subtype were as follows: ‘apocrine A’ (AR+/HER2−/Ki-67-low) (24%), ‘apocrine B’ (AR+/HER2−/Ki-67-high) (18%), ‘apocrine HER2’ (AR+/HER2+) (35%), ‘HER2-enriched’ (AR−/HER2+) (12%), and ‘double negative’ (AR−/HER2−) (11%). ‘Double negative’ was further subclassified into ‘basal-like’ (EGFR and/or CK5/6+) (7%) and ‘unclassified’ (3%). Consequently, patients with ‘apocrine A’ showed a better progression-free survival than those with any other subtypes. Our revised immunoprofiling classification was valuable for predicting the survival and might be useful in personalized therapy for patients with SDC.

The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas: a study of 142 cases

“…Oncology/College of American Pathologists (ASCO/CAP) guidelines for evaluating breast cancer . HER2, status as well the results of immunohistochemical staining for AR, Ki‐67 and PI3K/p‐Akt/mTOR/PTEN, which were reported previously by our group, were compared to the results obtained from the present study …”

The key radiologic and cytomorphologic features of oncocytic and oncocytoid lesions of the salivary gland

“…Commonly mutated genes in SDC include TP53 , PIK3CA , and HRAS as well as PTEN , which also may be lost . A subset of SDCs will demonstrate ERBB2 amplification . As a majority of PAs demonstrate rearrangements involving PLAG1 and HMGA2, these can be identified in the setting of SDC arising as carcinoma ex PA …”

Prediction of clinical benefit from androgen deprivation therapy in salivary duct carcinoma patients

“…Besides ADT, other treatment options are available for patients with R/M SDC. In the case of ERBB2 (HER2) gene amplification (29.4–46.4%), patients can be treated with docetaxel plus trastuzumab, showing an overall response rate of 70.2% and median PFS of 8.9 months . Double HER2 blockade with docetaxel–trastuzumab–pertuzumab or in second‐line with the antibody‐drug conjugate trastuzumab‐emtansine also showed promising results .…”