Abstract 5457: Prevalence of “low” HER2 expression is frequent in breast cancer but also in cancers of other origin: A tissue microarray study on 131 tumor types
Authors: Lennartz Maximilian , Viehweger Florian , Dum David , Uhlig Ria , Hinsch Andrea , Hoeflmayer Doris , Fraune Christoph , Bernreuther Christian , Lebok Patrick , Weidemann Soeren , Sauter Guido , Clauditz Till Sebastian , Jacobsen Frank , Krech Till , Marx Andreas H , Minner Sarah , Simon Ronald , Gorbokon Natalia , Steurer Stefan , Burandt Eike 
Published: June 2023

Abstract
HER2 is a receptor tyrosine-protein kinase coded by the ERBB2 gene. The HER2 status is routinely assessed to select patients eligible for targeted therapy with anti-HER2 drugs. HER2 positivity was restricted to cancers with a 3+ score at immunohistochemistry (IHC) and/or gene amplification. The successful use of HER2 antibody-drug conjugates in tumors with IHC scores of 1+ (HER2 low) or 0 with incomplete and faint staining in ≤10% of tumor cells (HER2 ultralow) is currently changing the traditional dichotomy of HER2 testing in breast cancer. To determine HER2 expression in neoplastic tissues, a tissue microarray containing one 0.6mm tissue spot each from 7,505 tumor samples from 131 different tumor types and subtypes was analyzed by immunohistochemistry. IHC scoring included 3+, 2+, 1+, and a category “+” (faintly positive in less than 10% of tumor cells; ultralow). The cohort included 310 breast cancers for which the HER2 amplification was also assessed by fluorescence in situ hybridization. Among 555 evaluable breast cancers, HER2 IHC was 3+ in 7.6%, 2+ in 3.2%, 1+ in 14.6%, “+” in 15.9% and 0 in 58.7%. The HER2 amplification rate was in 95.8% of 3+, 61.5% of 2+, 18.2% of 1+, but 0% in “+” and HER2 0 breast cancers. Among 4,912 non-breast cancers, the HER2 status was 3 in 0.6%, 2 in 0.7%, 1 in 3.3%, “+” in 2.3%, and 0 in 93.2%. In these tumors, 3+ positivity was largely restricted to gastric/esophageal adenocarcinoma, urothelial carcinoma, ovarian cancer as well as adenocarcinomas of the lung, colon, and pancreas. A 2+ positivity was mostly seen in tumor entities that had also 3+ cases. A 1+ or “+” HER2 positivity was found in 50 of 147 analyzed non-breast cancer categories. HER2 low and ultralow (1+ or “+”) was most commonly seen in basal cell carcinoma of the skin (52.2%), clear cell carcinoma of the ovary (33.3%), urothelial carcinoma of the renal pelvis (33.3%), gallbladder adenocarcinoma (26.7%), muscle-invasive urothelial carcinoma of the bladder (24.5%), prostatic adenocarcinoma, Gleason 4+4 (23.3%), endometrial serous carcinoma (22.7%), prostatic adenocarcinoma, Gleason 5+5 (19.2%), carcinosarcoma of the ovary (18.8%), renal oncocytoma (17.9%), serous carcinoma of the ovary (17.8%), gastric adenocarcinoma, intestinal type (13.2%), neuroendocrine tumor (NET) of the lung (11.1%), carcinosarcoma of the uterus (11.1%), endometrioid carcinoma of the ovary (11.1%), squamous cell carcinoma of the larynx (10.7%), parathyroid gland adenoma (10%), endometrioid endometrial carcinoma (9.7%), adenocarcinoma of the esophagus (9.5%), cholangiocarcinoma of the liver (9.3%), and pancreatic/ampullary adenocarcinoma (8.6%). While 3+ IHC is limited to only few cancer types, there is a much broader range of tumor entities that can show HER2 low and ultralow expression. HER2 antibody-drug conjugates may therefore be successful drugs in a large variety of different tumor entities.
Citation Format: Maximilian Lennartz, Florian Viehweger, David Dum, Ria Uhlig, Andrea Hinsch, Doris Hoeflmayer, Christoph Fraune, Christian Bernreuther, Patrick Lebok, Soeren Weidemann, Guido Sauter, Till Sebastian Clauditz, Frank Jacobsen, Till Krech, Andreas H Marx, Sarah Minner, Ronald Simon, Natalia Gorbokon, Stefan Steurer, Eike Burandt. Prevalence of “low” HER2 expression is frequent in breast cancer but also in cancers of other origin: A tissue microarray study on 131 tumor 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 5457.