Expression of proliferating cell nuclear antigen (PCNA) and Ki‐67 in soft tissue sarcoma. Is prognostic significance histotype‐specific?

Abnormal patterns of proliferation characterize the behavior of many tumors. Proliferating cell nuclear antigen (PCNA) and Ki‐67 are two cell cycle antigens which are expressed in proliferative states. Our study examines the prognostic value of these cell‐cycle antigens in soft tissue sarcoma (STS). Paraffin‐embedded primary tumor tissues from 185 patients (1980–92) were stained with the anti‐PCNA antibody PC‐10; 182 of these were stained with the antibody MIB‐1 for Ki‐67. Using PCNA (≤50; >50%) and Ki‐67 (≤10; >10%) indices, we examined and compared metastasis‐free survival (MFS) in a mixed‐histotype group, as well as after subdivision into MFH and non‐MFH groups. Fifty‐seven patients developed metastases. The median follow‐up for survivors was 6 (2–13) years. In the mixed series, the 2‐year MFS for a PCNA index ≤50 was 76%, and for an index >50 56%. Survival predicted by Ki‐67 index was comparable. PCNA index (but not Ki‐67) strongly correlated with the incidence of metastasis in MFH tumors and predicted 2‐year MFS of 81 vs 48%. In contrast, Ki‐67 index (but not PCNA) strongly correlated with metastasis in non‐MFH tumors and predicted 2‐year MFS survival of 90 vs 45%. No correlation existed between PCNA and Ki‐67 indices in the mixed histotype, MFH or non‐MFH groups. In combination, a high PCNA and Ki‐67 index correlated with poor survival, a high PCNA and lower Ki‐67 index (or vice versa) with an intermediate survival, and low PCNA and Ki‐67 indices with the best survival. The pattern of PCNA and Ki‐67 expression raises the possibility of histotype specificity.