Abstract 5554: Mammaglobin-A expression in highly specific for tumors derived from the breast, the female genital tract and salivary gland tumors

Abstract

Abstract Background: Human mammaglobin-A (SCGB2A2) is a small epithelial secretory protein with unknown function. Because of its frequent expression in breast epithelial cells, it is used as a diagnostic marker for breast cancer and represents an attractive target for novel therapies involving adaptive T cell transfer and antitumor vaccines for breast cancer patients. However, there is growing evidence that mammaglobin-A expression is not limited to breast cancers. Methods: In order to comprehensively determine mammaglobin-A expression in normal and neoplastic tissues, a tissue microarray containing 16,328 samples from 128 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: Mammaglobin-A positivity was found in 37 of 128 tumor categories, 32 of which were derived of one of four organs: breast (6 tumor categories), endometrium (5 tumor categories), ovary (5 tumor categories), and salivary glands (16 tumor categories). Only 5 additional tumor types showed occasional mammaglobin positivity. These tumors mostly exhibited a weak mammaglobin-A staining and included medullary thyroid cancer, teratoma of the testis, squamous cell carcinoma of skin and the pharynx, and prostatic adenocarcinoma (Gleason 5+5=10). Among 1,139 evaluable invasive breast carcinomas of no special type (NST), low mammaglobin-A immunostaining was linked to high BRE grade (p=0.0011), a loss of estrogen and progesterone receptor expression (p<0.0001 each), and triple negative status (p<0.0001) but not to patient survival. In endometrial cancer, low mammaglobin-A immunostaining was linked to advanced tumor stage (p=0.0198). Although a similar trend was seen for endometrioid and serous high-grade carcinomas of the ovary, these associations did not reach statistical significance. Conclusions: Our data characterize mammaglobin-A as a highly specific marker for tumors derived from either female organs or the salivary gland. The potential use of anti-Mammaglobin therapies should be studied also in other mammaglobin-positive tumor types. Citation Format: Natalia Gorbokon, Patrick Timm, David Dum, Anne Menz, Franziska Büscheck, Cosima Völkel, Andrea Hinsch, Maximilian Lennartz, Andreas Luebke, Claudia Hube-Magg, Christoph Fraune, Christian Bernreuther, Patrick Lebok, Till Clauditz, Frank Jacobsen, Guido Sauter, Ria Uhlig, Stefan Steurer, Sarah Minner, Andreas Marx, Ronald Simon, Eike Burandt, Till Krech. Mammaglobin-A expression in highly specific for tumors derived from the breast, the female genital tract and salivary gland tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5554.