Co-expression of CDX2 and MUC2 in gastric carcinomas: correlations with clinico-pathological parameters and prognosis.
OBJECTIVE
To evaluate the role of CDX2 homeobox protein as a predictor for cancer progression and prognosis as well as its correlation with MUC2 expression. CDX2 represents a transcription factor for various intestinal genes (including MUC2) and thus an important regulator of intestinal differentiation, which could previously be identified in gastric carcinomas and intestinal metaplasia.


METHODS
Formalin-fixed and paraffin-embedded tissues from 190 gastric carcinoma patients were stained with monoclonal antibodies recognizing CDX2 and MUC2, respectively. Immunoreactivity was evaluated semiquantitatively and statistical analyses including chi(2) tests, uni- and multi-variate survival analyses were performed.


RESULTS
CDX2 was mostly expressed in a nuclear or supranuclear pattern, whereas MUC2 showed an almost exclusive supranuclear reactivity. Both antigens were present in >80% of areas exhibiting intestinal metaplasia. An immunoreactivity in >5% of the tumor area was observed in 57% (CDX2) or in 21% (MUC2) of the carcinomas. The presence of both molecules did not correlate with WHO, Lauren and Goseki classification (with the exception of a significantly stronger MUC2 expression in mucinous tumors). CDX2 correlated with a lower pT and pN stage in the subgroups of intestinal and stage I cancers and was associated with MUC2 positivity. A prognostic impact of CDX2 or MUC2 was not observed.


CONCLUSIONS
CDX2 and MUC2 play an important role in the differentiation of normal, inflamed, and neoplastic gastric tissues. According to our results, loss of CDX2 may represent a marker of tumor progression in early gastric cancer and carcinomas with an intestinal phenotype.
Roessler
Kristina
K
Institute of Pathology, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50931 Cologne, Germany.
Mönig
Stefan-P
SP
Schneider
Paul-M
PM
Hanisch
Franz-Georg
FG
Landsberg
Stephanie
S
Thiele
Juergen
J
Hölscher
Arnulf-H
AH
Dienes
Hans-P
HP
Baldus
Stephan-E
SE
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D042241:Early Diagnosis; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055262:Mucin-2; D009077:Mucins / Q000378:metabolism*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins