IMMUNOSTAINING FOR PROLIFERATING CELL NUCLEAR ANTIGEN - ITS ROLE IN DETERMINATION OF PROLIFERATION IN ROUTINELY PROCESSED HUMAN BRAIN-TUMORSPECIMENS

Alcohol- and formalin-fixed, paraffin-embedded samples of 71 brain tum ors (35 gliomas, 22 metastatic carcinomas, a meningiomas and 6 other t umors) were investigated by immunocytochemistry with three different m onoclonal antibodies against proliferating cell nuclear antigen (PCNA) /cyclin (19A2; 19F4; PC10). PC10 was found to work best; it is applica ble to both alcohol- and formalin-fixed tumor samples. PCNA labeling i ndices (LIs) were compared in the same tumors with LIs obtained by Ki- 67 immunostaining of frozen sections and by in vitro incubation with b romodeoxyuridine (BrdUrd); in the latter preparations, BrdUrd LIs coul d be compared with PCNA LIs in the very same areas of serial sections. In gliomas, PCNA LIs were 0.7-80.2% (mean 31.7%), in metastases 0-76. 0% (mean 47.8%), and in meningiomas 0-53.0% (mean 19.3%). In general, PCNA LIs were highly significantly correlated with Ki-67 LIs (P = 0.00 02) and BrdUrd LIs (P = 0.0001). However, when tumor subgroups are con sidered, only gliomas show a significant correlation with Ki-67 and Br dUrd LIs. Despite this statistical correlation, PCNA expression was ou t of proportion to proliferation indices as determined by both other m ethods in almost one third of all brain tumors. Immunocytochemistry fo r PCNA produces a broad spectrum of staining intensity of labeled nucl ei, whose number is dependent upon the sensitivity of the immunocytoch emical technique used. Thus, inter-oberserver and inter-laboratory var iabilities in PCNA LI determination may occur. Overlapping of PCNA LIs between tumor subgroups of varying malignancy further limits the info rmational value for the individual case. In some classic meningiomas, high PCNA scores do not reflect the proliferative activity of the tumo r, as Ki-67 and BrdUrd LIs are very low in these cases. We conclude th at PCNA immunolabeling is of limited value in the individual tumor, ma inly due to overexpression in many tumors, and at present cannot be re commended to replace Ki-67 and/or BrdUrd labeling methods for routine determination of proliferative activity in human tumor specimens.