Predictive markers of chemoradiotherapy for rectal cancer: comparison of biopsy specimens taken before and about 1 week after the start of chemoradiotherapy.

Abstract

Preoperative chemoradiotherapy (CRT) significantly decreases local recurrence in patients with rectal cancer. Although various biomarkers in biopsy specimens obtained before starting CRT have been examined, reliable prognostic factors have yet to be established. We tested the hypothesis that biopsy specimens obtained soon after the start of CRT can be used as prognostic factors. Preoperative CRT was given to 70 consecutive patients with rectal cancer. Biopsies were taken before and about 7 days after starting CRT. The specimens were stained with hematoxylin and eosin (HE), and the expressions of Ki67, p53, and p21 and apoptosis were evaluated immunohistochemically. The expressions of Ki67, p53, and p21 and apoptosis before treatment were not significantly related to histologic response or tumor shrinkage. In specimens obtained about 7 days after CRT began, marked histologic regression was significantly higher in p21-positive, apoptosis-positive cases, and in cases with moderate changes on HE specimens (p = 0.017, p = 0.010, and p = 0.004, respectively). The tumor shrinkage was significantly higher in apoptosis-positive cases and cases with moderate changes on HE specimens (p = 0.002 and p < 0.001, respectively). Disease-free survival (DFS) was significantly higher in patients who had marked regression than in those who did not (p = 0.019). DFS was also significantly higher in patients with moderate changes on HE specimens than in those with mild changes (p = 0.016). Changes on HE-stained biopsy specimens obtained about 1 week after starting CRT are a reliable prognostic factor, similar to histologic marked regression in resected specimens; a major advantage is that the former results are available at an early phase.