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Concurrent expressions of metallothionein, glutathione S-transferase-π, and P-glycoprotein in colorectal cancers

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Diseases of the Colon & Rectum

Abstract

PURPOSE: Because the status of the inherent drug-resistance of colorectal cancers remains obscure, human colorectal cancers with no neoadjuvant therapy were retrospectively investigated regarding the expression of three drug-resistant proteins: metallothionein, glutathione S-transferase-π, and P-glycoprotein. METHODS: Paraffin-embedded tissues of 130 colorectal cancers (Dukes A, 20; B, 49; C, 41; D, 20) obtained by surgical resections from 1982 to 1989 were used. The three proteins were immunostained by the streptavidin-biotin complex method. The immunostaining was judged to be positive if more than 5 percent of cells showed positive staining by use of cell analysis system. The data were compared with clinicopathologic features (Dukes A-D) and patients' prognosis (Dukes A-C). RESULTS: Metallothionein, glutathione S-transferase-π, and P-glycoprotein were positively expressed in 91 (70 percent), 30 (23 percent), and 98 (75 percent), respectively. A total of 120 (86 percent) expressed at least one drug-resistant protein. No intergroup differences were observed between positive and negative expressions of the proteins and their clinicopathologic features except tumor location. Rectal cancers positively expressed P-glycoprotein and three proteins more frequently. Twenty-six (20 percent), 65 (50 percent), and 21 (16 percent) cancers positively expressed one, two, and three proteins, respectively. The disease-free survival rates of patients with Dukes A through C cancer with positive staining for one, two, and three proteins were 100, 94, and 83 percent (at 1 year); 100, 72, and 51 percent (at 3 years); and 94, 66, and 38 percent (at 5 years), respectively (Kaplan-Meier with log-rank test;P = 0.016). In the multivariate Cox analysis, age, Dukes stage, tumor size, and glutathione S-transferase-π were independent prognostic factors. CONCLUSIONS: The patients with concurrent expression of drug-resistant proteins in their cancers had worse prognoses. Examining drug-resistant proteins in colorectal cancers may be useful in selecting adjuvant chemotherapy and in predicting prognosis more accurately.

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Authors and Affiliations

  1. From the Second Department of Surgery, Shimane Medical University, Izumo City, Japan

    Ichiro Sutoh M.D., Hitoshi Kohno M.D., Yuuichi Nakashima M.D., Yoshitaka Hishikawa M.D., Hideki Tabara M.D., Mitsuo Tachibana M.D., Hirofumi Kubota M.D. & Naofumi Nagasue M.D.

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  1. Ichiro Sutoh M.D.
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  2. Hitoshi Kohno M.D.
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  3. Yuuichi Nakashima M.D.
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  7. Hirofumi Kubota M.D.
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Sutoh, I., Kohno, H., Nakashima, Y. et al. Concurrent expressions of metallothionein, glutathione S-transferase-π, and P-glycoprotein in colorectal cancers. Dis Colon Rectum 43, 221–232 (2000). https://doi.org/10.1007/BF02236987

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