Expression of the xenobiotic- and reactive oxygen species-detoxifying enzymes, GST-pi, Cu/Zn-SOD, and Mn-SOD in the endocrine cells of colorectal cancer

Abstract

Background and aim: The aim of the present work was to analyze the expression of antioxidant enzymes GST-pi, SOD1, and SOD2 in endocrine cells of colorectal cancers and to evaluate the significance of the presence of thus labeled endocrine cells as prognostic factor.

Methods: The expression of chromogranin A (ChGA), GST-pi, SOD1, and SOD2 was determined in endocrine cells of 128 colorectal cancers using light and electron immunohistochemistry and double immunogold labeling method.

Results: Endocrine cells expressing at least one of the studied antioxidant enzymes were detected in a relatively small proportion of primary colorectal cancers (22 cases, 17%; 14% GST-pi-positive, 14% SOD1-positive, and 9% SOD2-positive). The double immunogold staining and the following electron microscopy showed that GST-pi, SOD1, and SOD2 were co-localized with ChGA to the granules of most endocrine cells. The survival analyses revealed that patients with endocrine cells in primary tumor tissues expressing GST-pi had worse prognosis after the surgical therapy than those without GST-pi-positive endocrine cells (median of 22.70 vs. 49.43 months, p < 0.05, Log-rank test).

Conclusions: Most of the ChGA-positive endocrine cells in colorectal cancers also expressed some or all of the three studied antioxidant enzymes, GST-pi, SOD1, and SOD2. Moreover, patients having tumors with GST-pi-positive endocrine cells have an unfavorable prognosis. We suggest that not the neuroendocrine differentiation in general, but the presence in the tumors of endocrine cells with activated antioxidant defense and probably metabolically more active might determine a more aggressive type of cancer leading to worse prognosis for patients.