Abstract 5144: Prevalence and clinical significance of CBP deficiency and disturbed CBP expression in human cancer

CBP (CREB-binding protein) is a ubiquitously expressed multidomain protein with histone acetyltransferase and transcriptional co-activator activity. As a major histone modifier, it is involved in the regulation of thousands of genes. CBP has a complex role in cancer where both loss-of-function and overexpression can occur. To better comprehend the role of CBP expression in cancer, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. In normal tissues, a strong nuclear CBP staining was ubiquitously seen except few cell types. Among 12,255 evaluable tumors, CBP staining was completely absent (CBP deficiency) in 226 (1.84%) while 232 (1.89%) showed only a faint to moderate staining of a minority of cancer cells (substantial reduction, SR), 384 (3.13%) a 1+, 3,079 (25.12%) a 2+, and 8,334 (68.00%) a 3+ CBP positivity. CBP deficiency or SR was particularly common in pancreatic acinar cell carcinoma (23,5%), endometrioid endometrial carcinoma (22,8%), hepatocellular carcinoma (19.0%), urothelial carcinoma of the renal pelvis (17,4%), medullary carcinoma of the breast (14.3%), serous carcinoma of the endometrium (12.5%), neuroendocrine carcinoma of the pancreas (11.1%), and chromophobe renal cell carcinoma (10.7%). Less than 10% CBP deficient or SR cases were seen in 57 additional tumor categories. Among tumors with detectable CBP expression, low CBP expression levels were linked to advanced pT stage (p<0.0001), high UICC stage (p=0.0005), poor ISUP (p=0.0001), Thoenes (p=0.0001) and Fuhrman (p<0.0001) grades in clear cell renal cell carcinoma (ccRCC). In papillary RCC (pRCC), low CBP was associated with high UICC grade (p=0.0409) and distant metastasis (p=0.0022). Low CBP was furthermore associated with advanced pT stage (p=0.0003) in colorectal carcinoma and reduced overall survival (p=0.0236) in muscle-invasive urothelial carcinoma. High CBP expression was statistically related to nodal metastasis in pancreatic ductal adenocarcinoma (p=0,0201). CBP expression was not unequivocally related to clinico-pathological parameters in breast, ovarian, endometrial and gastric cancer. It is concluded, that CBP deficiency - as a rare event - occurs in many different tumor types and that a reduced or absent CBP expression is linked to aggressive cancer in multiple tumor entities. Citation Format: Viktoria Chirico, Seyma Büyücek, Katharina Möller, Florian Lutz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Elena Bady, Lisa Hornsteiner, Christian Bernreuther, Guido Sauter, Andreas H Marx, Till Krech, Stefan Steurer, Christoph Fraune, Sarah Minner, Natalia Gorbokon, Maximilian Lennartz, Eike Burandt, Anne Menz, Sören Weidemann, Waldemar WIlczak, Morton Freytag, Viktor Reiswich, Ronald Simon, Simon Kind, Ria Schlichter, Nina Schraps. Prevalence and clinical significance of CBP deficiency and disturbed CBP expression in human cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5144.