Cancer Res Treat.  2004 Dec;36(6):360-366.

Responsiveness of CPT-11 in Respect to hMLH1 and hMSH2 Protein Expression in the Primary Colorectal Cancer

• Park IJ
• Kim HC
• Yu CS
• Chang HM
• Lee JH
• Kim JH
• Kim TW
• Kim JS
• Kim JC

Abstract

PURPOSE
The aim of this study was to evaluate the responsiveness to CPT-11 with respect to hMLH1 and hMSH2 protein expressions in primary colorectal tumors. MATERIAL AND METHODS: 91 patients with colorectal cancer treated having undergone surgery and postoperative CPT-11-based adjuvant chemotherapy, between 1997 and 2002, were prospectively recruited. Tumor samples were immunohistochemically analyzed for the expressions of hMLH1, hMSH2, p53 and CEA proteins. RESULTS: Of the 91 tumors, 6 (6.6%) and 4 (4.4%) showed loss of hMLH1 and hMSH2 protein expressions, respectively. The response rate of patients with tumors not expressing either hMLH1 or hMSH2 was higher than that of those expressing either of these proteins (p=0.026). Patients with tumors not expressing hMLH1 showed a significantly better response to CPT-11 (p=0.04). The responsiveness was not associated with the expressions of hMSH2, p53 or CEA. There were no correlations between drug toxicity and the expressions of hMLH1, hMSH2 or p53. The overall survival was better in patients responsive to CPT-11-based chemotherapy compared to non-responders. CONCLUSION: The immunohistochemical determination of loss of hMLH1 and hMSH2 expressions may be used in determining the responsiveness to CPT-11-based chemotherapy. Our results suggest that hMLH1 protein expression may be a predictor for CPT-11 responsiveness in patients with colorectal cancer.

Keyword

Colorectal neoplasm; CPT-11; Response; hMLH1; hMSH2

MeSH Terms

Chemotherapy, Adjuvant
Colorectal Neoplasms*
Drug Therapy
Drug-Related Side Effects and Adverse Reactions
Humans
Prospective Studies

Figure

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  Fig. 1 hMLH1 and hMSH2 protein expressions, as assessed by nuclear immunohistochemical staining. (A) Tumor tissue positive for hMLH1 (brown stain). (B) Tumor tissue negative for hMLH1. (C) Tumor tissue positive for hMSH2 (brown stain). (D) Tumor tissue negative for hMSH2 (×200 magnification).

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  Fig. 2 Grading of p53 protein expression. (A) Grade 0. Tumor not expressing p53. (B) Grade 1. Small subsets of tumor cells expressing p53. (C) Grade 2. More than one third of tumor cells expressing p53. (D) Grade 3. More than two thirds of tumor cells expressing p53 (×200 magnification).

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  Fig. 3 Survival and p53 expression. Although the curve suggests better survival in the p53(+) group, the difference from the p53(-) group did not quite reach statistical significance (p=0.052).

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