17β-Hydroxysteroid dehydrogenase type 2: independent prognostic significance and evidence of estrogen protection in female patients with colon cancer

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 87; no. 2; pp. 133 - 140
• Main Authors: Oduwole, Olayiwola O., Mäkinen, Markus J., Isomaa, Veli V., Pulkka, Anitta, Jernvall, Petra, Karttunen, Tuomo J., Vihko, Pirkko T.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2003; Elsevier Science
• Subjects: Biological and medical sciences; Colon cancer; Fundamental and applied biological sciences. Psychology; In situ hybridization; Ki67; p53; Sex steroid hormones; Short-chain dehydrogenases/reductases; Vertebrates: endocrinology; Short-chain dehydrogenases/reductases; Sex steroid hormones; Colon cancer; In situ hybridization; Ki67; p53; Human; Prognosis; Digestive system; Enzyme; Gut; Estrogen; Malignant tumor; Dehydrogenase; Ovarian hormone; Female; Oxidoreductases; Colon; Sex steroid hormone; Protection
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2003.08.008

The mRNA expression of 17β-hydroxysteroid dehydrogenase (17HSD) types 1 and 2 enzymes catalyzing opposite reaction of estrogen metabolism was investigated in colon cancer. Further, the significance of the 17HSD type 2 enzyme as a possible marker of colorectal cancer (CRC) prognosis was studied. In the normal mucosa, 17HSD type 2 mRNA was predominantly expressed in the surface epithelium and in the upper parts of the crypts. In the lamina propria expression was seen in endothelial cells and mononuclear phagocytes. In colorectal tumors, 17HSD type 2 expression was in most cases downregulated. Female patients had significantly more cancers with high 17HSD type 2 mRNA expression (
n=11/35; 31%) than male patients (
n=3/39; 8%) (
P=0.02). We observed a significant impact of 17HSD type 2 mRNA expression on survival in female patients with distal colorectal cancer (
n=24), with an overall cumulative 5-year survival rate of 54% in those with low 17HSD type 2 mRNA expression. None of the female patients with high 17HSD type 2 mRNA expression survived (
n=11;
P=0.0068; log rank 7.32). In male patients, no significant association with survival was observed. Our data provide evidence suggesting that low 17HSD type 2 mRNA expression is an independent marker of favorable prognosis in females with distal colorectal cancer, supporting the presence of gender- and location-related differences in the pathogenesis of colon cancer.