Prostate-specific membrane antigen expression in the vasculature of primary lung carcinomas associates with faster metastatic dissemination to the brain

J Cell Mol Med. 2020 Jun;24(12):6916-6927. doi: 10.1111/jcmm.15350. Epub 2020 May 11.

Abstract

Glioblastomas and brain metastases (BM) of solid tumours are the most common central nervous system neoplasms associated with very unfavourable prognosis. In this study, we report the association of prostate-specific membrane antigen (PSMA) with various clinical parameters in a large cohort of primary and secondary brain tumours. A tissue microarray containing 371 cases of ascending grades of gliomas pertaining to astrocytic origin and samples of 52 cases of primary lung carcinomas with matching BM with follow-up time accounting to 10.4 years was evaluated for PSMA expression using immunohistochemistry. In addition, PSMA expression was studied in BM arising from melanomas and breast carcinomas. Neovascular expression of PSMA was evident alongside with high expression in the proliferating microvasculature of glioblastomas when compared to the tumour cell expression. This result correlated with the results obtained from the in silico (cancer genome databases) analyses. In gliomas, only the vascular expression of PSMA associated with poor overall survival but not the tumour cell expression. In the matched primary lung cancers and their BM (n = 52), vascular PSMA expression in primary tumours associated with significantly accelerated metastatic dissemination to the brain with a tendency towards poor overall survival. Taken together, we report that the vascular expression of PSMA in the primary and secondary brain tumours globally associates with the malignant progression and poor outcome of the patients.

Keywords: PSMA; brain metastasis; glioblastoma; proliferating microvasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Brain Neoplasms / metabolism*
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / blood supply
  • Glioma / pathology
  • Glutamate Carboxypeptidase II / genetics
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Lung Neoplasms / blood supply*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Progression-Free Survival
  • Prostate-Specific Antigen / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Antigens, Surface
  • RNA, Messenger
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Prostate-Specific Antigen