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Gut 2000;46:359-366 ( March )

Article

Altered mRNA expression of glycosyltransferases in human colorectal carcinomas and liver metastases T Petretti, W Kemmner, B Schulze, P M Schlag

Robert-Rössle-Klinik at the Max Delbrück Centre for Molecular Medicine, Department of Surgery and Surgical Oncology, Charité, Campus Buch, 13125 Berlin, Germany

Correspondence to: Dr W Kemmner, Max Delbrück Centre for Molecular Medicine, Robert-Rössle-Str 10, D-13092 Berlin, Germany wkemmner{at}mde-berlin.de

Accepted for publication 16 September 1999

BACKGROUND/AIMS---Biosynthesis of carbohydrate structures is tissue specific and developmentally regulated by glycosyltransferases such as fucosyltransferases, sialyltransferases, and N-acetylgluco- saminyltransferases. During carcinogenesis, aberrant glycosylation leads to the development of tumour subpopulations with different adhesion properties. Therefore alterations in glycosyltransferase mRNA expression in colorectal carcinomas were examined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).
METHODS---Colorectal carcinoma specimens were classified and characterised according to the WHO/UICC system. Expression of fucosyltransferases FT-I, FT-III, FT-IV, FT-V, FT-VI, and FT-VII, sialyltransferases ST3Gal-I, ST3Gal-III, ST3Gal-IV, and ST6Gal-I, beta 1,4-galacto- syltransferase, and beta 1,6-Nacetylgluco- saminyltransferase V (GNT-V) was screened simultaneously in extracts of 22 homogenised tumour specimens by RT-PCR and compared with corresponding mucosa from each patient. Also 12 adenomas and 17 liver metastases of colorectal carcinomas were examined.
RESULTS---GNT-V expression was enhanced in colorectal adenomas (p = 0.039), carcinomas (p<0.001), and liver metastases of colorectal carcinomas (p<0.001). Also, expression of fucosyltransferase FT-IV was increased in colorectal adenomas (p = 0.039) and carcinomas (p<0.001). In addition, fucosyltransferase FT-I (p<0.001) and sialyltransferases ST6Gal-I (p = 0.004) and ST3Gal-III (p = 0.001) showed increased expression in carcinoma specimens. On the other hand, fucosyltransferase FT-III was less abundantly expressed in carcinomas exhibiting distant metastases (p = 0.046) and in highly invasive tumours (p = 0.041).
CONCLUSIONS---Glycosyltransferase mRNA expression is significantly altered in colorectal adenomas and carcinomas isolated from surgical specimens. RT-PCR determination of specific glycosyltransferases may be helpful for earlier detection of carcinomas and for tumour prognosis.


Keywords: colorectal carcinoma; adenomas; liver metastasis; glycosyltransferases; tumour prognosis; mRNA expression

© 2000 by Gut


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