Preoperative chemoradiation
therapy (CRT) significantly decreases local recurrence in locally advanced
rectal cancer. Various
biomarkers in biopsy specimens obtained before CRT have been proposed as predictors of response. However, reliable
biomarkers remain to be established.
METHODS AND MATERIALS: The study group comprised 101 consecutive patients with locally advanced
rectal cancer who received preoperative CRT with oral
uracil/
tegafur (UFT) or S-1. We evaluated histologic findings on
hematoxylin and
eosin (H&E) staining and immunohistochemical expressions of Ki67, p53, p21, and apoptosis in biopsy specimens obtained before CRT and 7 days after starting CRT. These findings were contrasted with the histologic response and the degree of
tumor shrinkage.
RESULTS: In biopsy specimens obtained before CRT, histologic marked regression according to the Japanese Classification of
Colorectal Carcinoma (JCCC) criteria and the degree of
tumor shrinkage on barium enema examination (BE) were significantly greater in patients with p21-positive
tumors than in those with p21-negative
tumors (P=.04 and P<.01, respectively). In biopsy specimens obtained 7 days after starting CRT,
pathologic complete response, histologic marked regression according to both the
tumor regression criteria and JCCC criteria, and T downstaging were significantly greater in patients with apoptosis-positive and p21-positive
tumors than in those with apoptosis-negative (P<.01, P=.02, P=.01, and P<.01, respectively) or p21-negative
tumors (P=.03, P<.01, P<.01, and P=.02, respectively). The degree of
tumor shrinkage on both BE as well as MRI was significantly greater in patients with apoptosis-positive and with p21-positive
tumors than in those with apoptosis-negative or p21-negative
tumors, respectively. Histologic changes in H&E-stained biopsy specimens 7 days after starting CRT significantly correlated with
pathologic complete response and marked regression on both JCCC and
tumor regression criteria, as well as with
tumor shrinkage on BE and MRI (P<.01, P<.01, P<.01, P<.01, and P=.03, respectively).
CONCLUSIONS: Immunohistochemical expressions of p21 and apoptosis together with histologic changes on H&E-stained biopsy specimens obtained 7 days after starting CRT are strong predictors of the response to CRT.