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. 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.
Oduwole
Olayiwola O
OO
Biocenter Oulu, Research Center for Molecular Endocrinology, WHO Collaborating Centre for Research on Reproductive Health, P.O. Box 5000, University of Oulu, FIN-90014 Oulu, Finland.
Mäkinen
Markus J
MJ
Isomaa
Veli V
VV
Pulkka
Anitta
A
Jernvall
Petra
P
Karttunen
Tuomo J
TJ
Vihko
Pirkko T
PT
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004960:Estradiol Dehydrogenases; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012737:Sex Factors; D015996:Survival Rate
D004967:Estrogens; D007527:Isoenzymes; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human