Abstract 7226: Tumor cell ICAM-1 expression is frequent in many tumor entities and linked to unfavorable tumor phenotype in renal cell carcinomas

Abstract Intercellular Adhesion Molecule 1 (ICAM-1; CD54) is a transmembranous glycoprotein with roles in immune surveillance, inflammation, cell signaling, and apoptotic processes. ICAM-1 is considered a stemness marker in cancer which is often expressed on cancer cells. It can modulate anti-cancer immune response or facilitate metastasis through interactions with immune cells and the extracellular matrix. Because of its surface expression, ICAM-1 is also being explored as a therapeutic target. To better comprehend the role of ICAM-1 expression on tumor cells in different cancer types, ICAM-1 was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 5,946 samples from 105 different tumor types. A total of 85 of 105 tumor categories showed ICAM-1 expression in at least one case, and 70 tumor categories contained at least one strongly positive case. Strong ICAM-1 positivity was most seen in several subtypes of lymphomas (up to 98.0%), metastatic malignant melanoma (87.7%), clear cell renal cell carcinoma (ccRCC; 79.8%), clear cell (tubulo) papillary RCC (75.0%), squamous cell carcinomas of the penis (68.5%), oral cavity (62.8%), esophagus (56.7%), pharynx (54.5%), larynx (54.0%), anal canal (53.4%), urinary bladder (47.6%), cervix (46.3%), and the vulva (43.0%), hepatocellular carcinoma (55.3%), muscle-invasive urothelial carcinoma of the bladder (47.4%), papillary RCC (pRCC; 40.6%), cholangiocarcinoma of the liver (27.3%), intestinal type gastric adenocarcinoma (25.7%), and in serous high-grade ovarian carcinoma (25.4%). Within 1,337 evaluable ccRCCs, ICAM-1 positivity was considered strong in 79.7%, moderate in 11.7%, weak in 6.7%, and absent in 1.9%. High ICAM-1 expression was associated with unfavorable ISUP grade (p<0.0001), advanced pT stage (p<0.0001), high UICC stage (p=0.0002), and distant metastasis (M1, p=0.0181). Within 370 pRCCs, ICAM-1 positivity was strong in 40.0%, moderate in 21.1%, weak in 25.9%, and absent in 13.0%. High ICAM-1 positivity was associated with poor ISUP grade (p<0.0001) and also tended to correlate with high pT stage (p=0.0861) and UICC stage (p=0.0890). It is concluded that ICAM-1 expression on tumor cells occurs commonly in many cancer entities. That high ICAM-1 expression was linked to unfavorable tumor features in RCCs supports the concept of a role of ICAM-1 expression for cancer progression. Citation Format: Clara von Bargen, Finn Wickel, Katharina Möller, Florian Lutz, Florian Viehweger, Georgia Makrypidi-Fraune, Martina Kluth, Claudia Hube-Magg, Christina Tsourlakis, Christian Bernreuther, Guido Sauter, Andreas H Marx, Ronald Simon, Stefan Steurer, Christoph Frauen, Nina Schraps, Fiete Gehrisch, Viktoria Chirico, Bertram Veith, Clara Luehr, Cosima Völkel, Morton Freytag, Natalia Gorbokon, Maximilian Lennartz, Eike C. Burandt, Anne Menz, Till Krech. Tumor cell ICAM-1 expression is frequent in many tumor entities and linked to unfavorable tumor phenotype in renal cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7226.