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

CBP (CREB-binding protein) is a ubiquitously expressed major histone modifier involved in the regulation of thousands of genes. In cancer, loss-of-function and overexpression can occur. To clarify the role of CBP expression, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissues was analyzed by immunohistochemistry. In normal tissues, strong nuclear CBP staining was ubiquitously seen except of 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 faint to moderate staining of a minority of cancer cells (substantial reduction, SR), 384 (3.13 %) weak, 3079 (25.12 %) moderate, and 8334 (68.00 %) strong CBP positivity. CBP deficiency or SR was common in endometrioid endometrial carcinoma (22.8 %), hepatocellular carcinoma (19.0 %), urothelial carcinoma (up to 17.4 %), serous endometrial carcinoma (12.5 %), and chromophobe renal cell carcinoma (RCC; 10.7 %). Less than 10 % CBP deficient or SR cases were seen in >50 additional tumor categories. Among tumors with CBP expression, reduced expression was linked to high pT (p < 0.0001), high UICC stage (p = 0.0005) and poor grade (p < 0.0001) in clear cell RCC, high UICC stage (p = 0.0409) and distant metastasis (p = 0.0022) in papillary RCC, advanced pT stage (p = 0.0003) in colorectal carcinoma and invasive disease (p < 0.0001) and L1 status (p = 0.0154) in urothelial carcinoma. High CBP expression was related to nodal metastasis in pancreatic adenocarcinoma (p = 0.0201). In conclusion, CBP deficiency is a rare event in many different tumor types. Reduced or absent CBP expression is linked to aggressive cancer phenotypes.