- 作者：Toshiyuki Suzuki ; MD ; PhD&lowast ; ; Sotaro Sadahiro ; MD ; PhD&lowast ; ; sadahiro@is.icc.u-tokai.ac.jp ; Akira Tanaka ; MD ; PhD&lowast ; ; Kazutake Okada ; MD&lowast ; ; Hiroko Kamata ; MD&lowast ; ; Akemi Kamijo ; BS&lowast ; ; Chieko Murayama ; PhD&dagger ; ; Takeshi Akiba ; MD&Dagger ; ; Shuichi Kawada ; MD&Dagger ;
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2013
- 出版时间：1 April, 2013
- 年：2013
- 卷：85
- 期：5
- 页码：1232-1238
- 全文大小：576 K
Purpose
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.