Abstract 2212: Prevalence of PGP9.5 expression in human cancers: A TMA study of 14,900 tumors from 148 tumor types

Abstract

Abstract The ubiquitin C-terminal hydrolase L1 (UCH-L1), also termed protein gene product 9.5 (PGP9.5) is an important component of the ubiquitination/deubiquitination system and plays a role in the posttranslational modification of proteins including protein degradation, relocation and change of function. Altered PGP9.5 expression has been suggested to play a role for resistance to chemotherapy, metastasis, and patient prognosis in several tumor entities. To comprehensively determine PGP9.5 expression in normal and neoplastic tissues, a tissue microarray containing 14,913 samples from 148 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. PGP9.5 immunostaining was found in 2,667 of 11,062 analyzed tumors and considered weak in 9.8%, moderate in 5.8% and strong in 8.5% of tumors. 113 of 148 tumor categories showed at least one positive case, and 90 of these tumor categories contained at least one case with strong PGP9.5 staining. PGP9.5 positivity was most seen in various types of neuronal and neuroendocrine neoplasms (71.1-100%), germ cell neoplasms of the testis (82.1%), and in mesotheliomas (74%). PGP9 positivity was seen in 14.2% of 606 clear cell and in 45.4% of 255 papillary renal cell carcinomas (RCC). In clear cell RCC, strong PGP9.5 staining was associated with high ISUP grade (p<0.0001), pT stage (p=0.0012), nodal (p=0.038) and distant metastasis (p<0.0001) as well as with a shortened overall, tumor specific and recurrence free survival (p<0.0001 each). In papillary RCC, strong PGP9.5 staining was significantly associated with high ISUP grade (p=0.009), advanced UICC stage (p=0.015), and shortened recurrence free survival (p<0.0001). In urothelial carcinoma of the urinary bladder, high PGP9.5 expression was associated with muscle-invasion (p<0.0001) but PGP9.5 immunostaining was unrelated to prognosis in pT2-4 carcinomas. In a joint analysis of 527 squamous cell carcinomas from 11 different sites of origin, PGP9.5 positivity was associated with high tumor grade (p=0.0021). PGP9.5 immunostaining was unrelated to pT and pN status in 207 serous high-grade and 82 endometrioid ovarian carcinoma, in 221 endometrioid endometrium cancer as well as in 292 papillary and in 89 follicular thyroid carcinomas. In ductal adenocarcinomas of the pancreas and in 356 gastric adenocarcinomas, PGP9.5 staining was unrelated to grade, pT and pN stage. Our data provide an overview on prevalence of PGP9.5 expression in cancer. PGP9.5 expression occurs commonly in many different tumor entities. PGP9.5 overexpression is strikingly linked to patient outcome in some tumor entities (i.e. clear cell RCC) but appears to be unrelated to unfavorable tumor characteristics in various other important tumor entities (i.e. gastric, pancreatic, ovarian cancer). Citation Format: Sekander Scherzai, Maximilian Lennartz, Frank Jacobsen, Florian Viehweger, David Dum, Anne Menz, Ria Uhlig, Andrea Hinsch, Doris Hoeflmayer, Christoph Fraune, Christian Bernreuther, Patrick Lebok, Soeren Weidemann, Guido Sauter, Till Sebastian Clauditz, Till Krech, Andreas H Marx, Ronald Simon, Stefan Steurer, Eike Burandt, Natalia Gorbokon, Sarah Minner. Prevalence of PGP9.5 expression in human cancers: A TMA study of 14,900 tumors from 148 tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2212.