Purpose: It has recently been demonstrated that the tumor growth rate is a stronger determinant of survival than the extent of the growth in local recurrence of rectal cancer. We studied which factors controlled the tumor growth rate using modern immunohistochemical methods.
Methods: In 51 patients who underwent extended resection for this condition, paraffin-embedded specimens were examined for 1) tumor angiogenesis by CD31 staining and microvessel counting, 2) apoptosis by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining, and 3) cellular proliferative activity using anti-proliferative cell nuclear antigen antibody. The results were compared with carcinoembryonic antigen doubling time and survival.
Results: The five-year survival rate was 20 percent. The postoperative carcinoembryonic antigen doubling time, which was the strongest predictor of survival, correlated highly with proliferative cell nuclear antigen labeling index, but did not correlate with the apoptotic index or microvessel counts.
Conclusion: Our study shows that cancer cell proliferation rather than apoptosis or angiogenesis is a major determinant of tumor growth rate and survival in patients with locally recurrent rectal cancer.