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

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.