INTRATUMORAL HETEROGENEITY AND INVERSE CORRELATION BETWEEN EXPRESSIONOF E-CADHERIN AND COLLAGENASE TYPE-IV IN HUMAN GASTRIC CARCINOMAS

We examined the expression of E-cadherin and collagenase type IV in fo rmalin-fixed, paraffin-embedded specimens of human gastric carcinoma b y an in situ mRNA hybridization (ISH) technique. The ISH technique rev ealed intertumoral heterogeneity for expression of E-cadherin and coll agenase among 12 cases of early gastric cancer and 13 cases of advance d gastric cancer. In the majority of the tumors, we found an inverse r elationship between the reactivities of E-cadherin and collagenase typ e IV. Specifically, E-cadherin was expressed at higher levels in the c enter of the neoplasms than in their periphery, whereas collagenase ty pe IV was expressed at a higher level in the periphery (invasive edge) than in the center. Advanced gastric cancers with high levels of expr ession for collagenase type IV in the periphery had a higher incidence of distant lymph node metastasis than those with low expression. The data show an inverse relationship between E-cadherin (involved in cell -to-cell adhesion) and collagenase type IV (involved in invasion) in d ifferent zones of human gastric carcinoma and suggest that the relativ e expression of these independent genes may be involved in local invas ion and metastasis.