CD44v6: a potential marker of malignant transformation in intestinal metaplasia of the stomach? An immunohistochemical study using tissue microarrays.
OBJECTIVE
Intestinal metaplasia is a well-established risk factor in the development of stomach cancer. However, since the specificity is low it would be of great practical value to find a marker to separate cases of intestinal metaplasia into low and high risk for progression to dysplasia/carcinoma. So far this has not been achieved. CD44 is a cell surface molecule involved in cell-cell and cell-matrix interactions, and the spliced variant 6 has been shown to play a role in the progression of gastric carcinoma. The aim of this study was therefore to evaluate CD44v6 as a marker of increased cancer risk in intestinal metaplasia.


METHODS
The current study investigated immunohistochemical CD44v6 expression in biopsies of normal gastric mucosa (n = 154) and gastric mucosa with intestinal metaplasia (n = 127). A third group consisted of cancer gastrectomies (n = 117) in which both tumour and uninvolved mucosa was studied. Proximal (cardia) and distal (corpus/antrum) locations were noted in all cases.


RESULTS
There was a significant sequential increase in CD44v6 expression from normal mucosa and mucosa showing intestinal metaplasia to uninvolved mucosa adjacent to cancers without and with intestinal metaplasia to tumour. The most striking increase was from 'normal' to intestinal metaplastic mucosa adjacent to cancers. There were no differences between proximal and distal cases in any group.


CONCLUSIONS
These findings strongly suggest that CD44v6 expression is a late phenomenon in the transformation of intestinal metaplasia to dysplasia/cancer. It may therefore be a useful marker of cancer risk in patients with intestinal metaplasia.
Gulmann
Christian
C
Department of Pathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland. cgulmann@rcsi.ie
Grace
Antoinette
A
Leader
Mary
M
Butler
David
D
Patchett
Stephen
S
Kay
Elaine
E
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008679:Metaplasia / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism*; D040081:Protein Array Analysis / Q000379:methods; D013274:Stomach Neoplasms / Q000378:metabolism*
D014408:Biomarkers, Tumor; C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins