RECTAL-CANCER - THE INFLUENCE OF TUMOR PROLIFERATION ON RESPONSE TO PREOPERATIVE IRRADIATION

Purpose: Regression of rectal carcinoma after preoperative irradiation is variable, likely reflecting differences in the physical and biolog ic properties of these tumors, This study examines the association bet ween the pathologic response of rectal cancer after irradiation and it s pretreatment proliferative state as assayed by the activity of the p roliferative dependent antigens (Ki-67, PCNA) and mitotic counts. Meth ods and Materials: One hundred and twenty-two patients with locally ad vanced rectal cancer received preoperative irradiation followed by sur gery, Pretreatment tumor biopsies were scored for the extent of Ki-67 and PCNA immunostaining and the number of mitoses per 10 high-powered fields, Postirradiation surgical specimens were examined for extent of residual disease. Results: The tumors of 38 of 122 patients (31%) exh ibited marked pathologic downstaging (no residual tumor or cancer conf ined to the rectal wall) after preoperative irradiation, Two features were associated with the likelihood of marked pathologic regression af ter preoperative irradiation: tumor proliferative activity and lesion size, When stratified by lesion size, marked tumor regression occurred most frequently in smaller tumors with high Ki-67, PCNA, and mitotic activity compared to larger tumors with lower Ki-67, PCNA, and mitotic activity, Intermediate downstaging rates were seen for small or large tumors with moderate Ki-67, PCNA, and mitotic activity. Conclusion: T umor Ki-67, PCNA, and mitotic activity predicts the likelihood of resp onse to irradiation, which may aid in formulating treatment policies f or patients with rectal cancer.