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

PURPOSE: Because the status of the inherent drug-resistance of colorectal c ancers remains obscure, human colorectal cancers with no neoadjuvant therap y were retrospectively investigated regarding the expression of three drug- resistant proteins: metallothionein, glutathione S-transferase-pi and P-gly coprotein. METHODS: Paraffin-embedded tissues of 130 colorectal cancers (Du kes A, 20; B, 49; C, 41; D, 20) obtained by surgical resections from 1982 t o 1989 were used. The three proteins were immunostained by the streptavidin -biotin complex method. The immunostaining was judged to be positive if mor e 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 AC). RESULTS: Metallothionein, glutathione S -transferase-pi; and P-glycoprotein were positively expressed in 91 (70 per cent), 30 (23 percent), and 98 (75 percent), respectively. A total of 120 ( 86 percent) expressed at least one drug-resistant protein. No intergroup di fferences were observed between positive and negative expressions of the pr oteins and their clinicopathologic features except tumor location. Rectal c ancers positively expressed P-glycoprotein and three proteins more frequent ly. Twenty-six (20 percent), 65 (50 percent), and 21 (16 percent) cancers p ositively expressed one, two, and three proteins, respectively. The disease -free survival rates of patients with Dukes A through C cancer with positiv e staining for one, two, and three proteins were 100, 94, and 83 percent (a t 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). I n the multivariate Cox analysis, age, Dukes stage, tumor size, and glutathi one S-transferase-pi were independent prognostic factors. CONCLUSIONS: The patients with concurrent expression of drug-resistant proteins in their can cers had worse prognoses. Examining drug-resistant proteins in colorectal c ancers may be useful in selecting adjuvant chemotherapy and in predicting p rognosis more accurately.