PGP9.5 expression in human tumors: A tissue microarray study on 13,920 tumors from 120 different tumor entities

Abstract

The protein gene product 9.5 (PGP9.5), also termed ubiquitin C-terminal hydrolase L1 (UCH-L1) is an important component of the ubiquitination/deubiquitination system and plays a role in axonal transport. To comprehensively determine PGP9.5 expression in neoplastic tissues, a tissue microarray containing 13,920 samples from 120 different tumor types and subtypes was analyzed by immunohistochemistry (IHC). PGP9.5 immunostaining was found in 109 of 120 tumor categories, 87 of which contained at least one strongly positive case. PGP9.5 positivity was most seen in neuronal and neuroendocrine neoplasms (50–100 %), germ cell neoplasms (28–84 %), sarcomas and carcinosarcomas (up to 91 %), and in mesotheliomas (58–83 %). In clear cell RCC (renal cell carcinomas), strong PGP9.5 staining was associated with high ISUP (International Society of Urological Pathology) grade (p<0.0001), advanced pT stage (p=0.0003), nodal (p=0.0242) and distant metastasis (p<0.0001) as well as with a short overall, tumor specific and recurrence free survival (p≤0.0007 each). In papillary RCC, strong PGP9.5 staining was associated with high ISUP grade (p=0.009) and reduced recurrence free survival (p=0.0221). In urothelial carcinoma of the urinary bladder, high PGP9.5 expression was associated with muscle-invasion (p<0.0001). PGP9.5 immunostaining was unrelated to histological parameters for tumor aggressiveness in 295 serous high-grade ovarian carcinomas, 174 endometrioid endometrium carcinomas, 292 papillary and 89 follicular thyroid carcinomas, 405 ductal adenocarcinomas of the pancreas and in 327 gastric adenocarcinomas. In summary, our data provide a comprehensive overview of PGP9.5 expression in cancer and demonstrate positive cases in a broad range of entities. PGP9.5 overexpression is linked to patient outcome in some tumor entities (i.e., clear cell RCC) but appears to be unrelated to clinically relevant tumor characteristics in many other frequent tumor entities.