Proliferating cell nuclear antigen expression in central nervous system neoplasms

Abstract

Proliferating cell nuclear antigen (PCNA) is a cell-cycle-regulated protein, which can be demonstrated in routinely fixed specimens. Studies on various tissues, cell cultures and neoplasms have shown that PCNA labelling index (LI) correlates with flow cytometry, tritiated thymidine LI, bromodeoxyuridine (BrdU) incorporation and Ki67 LI. PCNA LI may have prognostic value in various neoplasms. The present study concerns PCNA immunostaining in a series of neuroglial tumours. We demonstrate that there is a relation between PCNA LI and histological grade, and between PCNA LI and reported thymidine LI, BrdU LI and Ki67 LI. Pleomorphic xanthoastrocytomas and low-grade astrocytomas had the lowest LI, whereas metastases of small cell lung cancer and medulloblastomas had the highest LI. Glioblastomas sometimes showed a certain degree of intratumoral heterogeneity of distribution of immunostained cells. Intratumoral heterogeneity underscores the critical importance of representative sampling of central nervous system neoplasms for kinetic studies. As expected, PCNA LI are somewhat higher than tritiated thymidine LI, BrdU LI and Ki67 LI because PCNA is a marker of G1, S, G2 and M-phases of the cell cycle and not of S-phase only. In addition, because of its long half-life, PCNA may be detected immunohistochemically in cells that have recently left the cell cycle. The immunohistochemical evaluation of PCNA LI is easy to perform on routinely processed material, allowing retrospective studies. PCNA LI may be a useful tool in grading gliomas. However, its prognostic value must be validated by comparing PCNA LI with the follow-up of the neoplasms, and possibly with the responsiveness to anti-proliferative therapy.