RETINOBLASTOMA PROTEIN EXPRESSION AND MIB-1 CORRELATE WITH SURVIVAL OF PATIENTS WITH MALIGNANT ASTROCYTOMA

BACKGROUND. Regulatory coupling of cell proliferation and apoptosis is suggested by recent findings with regard to certain tumors, such as t he finding of tumor resistance to anticancer therapy caused by inhibit ion of apoptosis. The processes leading to apoptosis appear to be regu lated by a variety of oncogenes and tumor suppressor genes. In the cur rent study, the relation between apoptosis and expression of retinobla stoma protein (pRB) was assessed in 50 primary anaplastic astrocytomas (AAs) and 46 recurrent tumors in the same patients as the primary tum ors after macroscopic total surgical resection and chemoradiotherapy. METHODS. Apoptotic cells were identified by the in situ 3'-end labelin g technique. Proliferative potential, pRB expression, and p53 expressi on were evaluated immunohistochemically using anti-Ki-67 (MIB-1), anti -pRB, and anti-p53 antibodies, respectively. The prognostic value of t hese biologic markers in AA patients undergoing treatment was also eva luated. RESULTS. The mean apoptotic index (AI) was 0.91 +/- 0.70% for specimens obtained at the initial surgery and 2.32 +/- 1.71% for those obtained at recurrence. There was no apparent correlation between the AI and the MIB-1 staining index (MI) in primary AAs, whereas signific antly higher AI and MI were observed in recurrent PRE negative cases t han in their pRB positive counterparts. The survival of patients with AAs showing a high MI and negative pRB immunostaining was significantl y shorter than in the other cases. Neither the size of the apoptotic f raction nor the p53 expression in primary tumor correlated with the ov erall survival. CONCLUSIONS. The clinical outcome of patients with AA may be associated with aberrant pRB function and increased proliferati ve activity rather than an inability of tumor cells to undergo apoptos is. (C) 1997 American Cancer Society.