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Estrogen receptor alpha (ER) is a nuclear transcription factor with a pivotal role in the function of the reproductive organs and of other organ systems. It constitutes a well-established therapeutic target for various small molecules. ER immunohistochemistry is used in surgical pathology for the distinction of tumors of the breast and gynecological organs. To comprehensively determine ER expression in normal and neoplastic tissues, a tissue microarray containing 18,560 samples from 149 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. ER positivity was found in 55 of 149 tumor categories, and 27 of these tumor categories contained at least one case with strong ER staining. ER positivity was most seen in various subtypes of breast cancer (78.9-95.7%) and in several different tumor categories of the ovary and the endometrium (8.5-75.9%). Other commonly ER positive tumor entities included leiomyoma (65.9%), neuroendocrine tumor of the appendix (43.8%), leiomyosarcoma (22.9%), Sertoli Leydig cell tumor of the ovary (1 of 3 positive), rhabdomyosarcoma (16.7%), angiomyolipoma (10%), colorectal neuroendocrine carcinoma (9.1%), myoepithelial carcinoma of the salivary gland (8.3%), granulosa cell tumor of the ovary (8.3%), epithelial-myoepithelial carcinoma of the salivary gland (7.7%), squamous cell carcinomas of various sites of origin (0.8-6.7%), testicular teratoma (5.3%), Brenner tumor of the ovary (5.1%), Ewing sarcoma (5%), adenocarcinoma NOS of the salivary gland (4.8%), papillary thyroid carcinoma (3.3%), sarcoma, not otherwise specified (NOS) (2.8%), paraganglioma (2.6%), non-invasive papillary urothelial carcinoma, pTa G3 (2.4%), pulmonary adenocarcinoma (2.1%), neuroendocrine tumor of the ileum (2.1%), and adenocarcinoma of the prostate, Gleason 5+5 (1.2%). Among 1,411 evaluable invasive breast carcinomas of no special type (NST), absent or low ER immunostaining was significantly linked to high BRE grade (p Citation Format: Florian Viehweger, David Dum, Anne Menz, Ria Uhlig, Andrea Hinsch, Doris Hoeflmayer, Christoph Fraune, Christian Bernreuther, Patrick Lebok, Soeren Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till Sebastian Clauditz, Till Krech, Andreas H Marx, Ronald Simon, Stefan Steurer, Sarah Minner, Eike Burandt, Natalia Gorbokon. Patterns of estrogen receptor expression across 18,500 tumor samples obtained from 149 cancer types [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 2164.