Assessment of biomarkers in paired primary and recurrent colorectal adenocarcinomas

Purpose: Recurrent colorectal cancers respond poorly to anticancer treatmen t including radiotherapy. To better understand the biological characteristi cs of the recurrent colorectal tumor, we investigated various biomarkers re gulating cell proliferation and cell loss in paired primary and recurrent c olorectal tumor specimens within each individual. Methods and Materials: From a total of 11 colorectal adenocarcinoma patient s, 22 specimens of paired primary and recurrent tumors were obtained for an alysis. Apoptosis was evaluated by TUNEL labeling of apoptotic DNA fragment ation. Other biomarkers including proliferating cell nuclear antigen (PCNA) , p53, WAF1, p34cdc2, and cyclins B1 and D1 were analyzed by immunohistoche mical stains. Results: PCNA index (PCNAI) showed an increase in 6 and a decrease in 5 rec urrent tumors compared to primary tumors. Median PCNAI in primary and recur rent tumors were 33.5 and 48.3, respectively (p = 0.16). In contrast, the a poptotic index (AI) decreased in 9 of 11 recurrent tumors compared to prima ry tumors. Median AI decreased from 4.3 in primary tumors to 1.4 in recurre nt tumors (p, = 0.04). The p53 expression increased in more than half of re current tumors compared to primary tumors. Mean staining score increased fr om 0.7 in primary tumors to 1.2 in recurrent tumors (p = 0.059). WAF1 and c yclin B1 did not show significant change. In contrast, both cyclin D1 and p 34cdc2 increased significantly in recurrent tumors. These two biomarkers sh owed increased expression in 8 (cyclin D1) and 7 (p34cdc2) recurrent tumors , respectively, compared to their primary counterparts. Mean staining score s of both biomarkers in recurrent tumors increased by more than twofold com pared to those in primary tumors and these differences were statistically s ignificant (cyclin D1, p = 0.007; p34cdc2, p = 0.008). Conclusion: This study showed significantly decreased apoptosis in recurren t colorectal tumors compared to their primary counterparts. The underlying regulatory mechanisms included increased expression of p53 and altered cell cycle regulators such as increased cyclin D1 and p34cdc2. With further stu dy, it may be used for developing a new therapeutic strategy for the treatm ent of recurrent colorectal cancer. (C) 1999 Elsevier Science Inc.