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

The mRNA expression of 17beta-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. I...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of steroid biochemistry and molecular biology 2003-11, Vol.87 (2-3), p.133-140
Main Authors: Oduwole, Olayiwola O, Mäkinen, Markus J, Isomaa, Veli V, Pulkka, Anitta, Jernvall, Petra, Karttunen, Tuomo J, Vihko, Pirkko T
Format: Article
Language:English
Subjects:
17-Hydroxysteroid Dehydrogenases - genetics
17-Hydroxysteroid Dehydrogenases - metabolism
Adult
Aged
Aged, 80 and over
Colonic Neoplasms - enzymology
Colonic Neoplasms - genetics
Colonic Neoplasms - pathology
Estradiol Dehydrogenases
Estrogens - metabolism
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Isoenzymes - metabolism
Male
Middle Aged
Neoplasm Staging
Prognosis
Proportional Hazards Models
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Sex Factors
Survival Rate
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The mRNA expression of 17beta-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.
ISSN:0960-0760