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E-Cadherin and -Catenin Expression in Human Esophageal Cancer¹

Department of Surgery II, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 [T. K., H. S., M. I., S. T., H. O., Y. D., K. I., S. M., T. I., T. M.], and Department of Information Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, Aichi 444 [A. N., S. T.], Japan

² To whom requests for reprints should be addressed.

Intercellular adhesion of the epithelial tissue is mainly regulated by the E-cadherin (E-cad) molecule. -Catenin (-cat) is one of the E-cad-associated cytoplasmic proteins that forms a linkage to the cytoskeleton and regulates E-cad function. To investigate the mechanism of dysfunction in cell-cell adhesion in cancerous tissues, we examined E-cad and -cat expression by immunohistochemical staining on 46 human esophageal cancers using our specific monoclonal antibodies.

By grading of E-cad and -cat expression as uniformly positive (+), heterogeneous (±), or uniformly negative (–), the 46 tumors could be classified into 9 (20%) E-cad(+)/-cat(+), 15 (33%) E-cad(±)/-cat(±), 21 (46%) E-cad(±)/-cat(–), and 1 (2%) E-cad(–)/-cat(–). Twenty-five (54%) of the 46 tumors showed a similar expression of both molecules, while the other 21 tumors (46%) showed E-cad(±)/-cat(–). Thus, although the expression of -cat was significantly correlated with that of E-cad, in some tumors the reduction of -cat was greater.

Regarding the clinicopathological features, the reduction of -cat expression, as well as that of E-cad, was significantly associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis (P < 0.01). Furthermore, the frequency of lymph node metastasis in E-cad(±)/-cat(–) tumors was significantly higher (90%) than in E-cad(+)/-cat(+) tumors (22%) (P < 0.01) or in E-cad(±)/-cat(±) tumors (47%) (P < 0.05).

These results suggest that not only E-cad but also -cat are important regulators of intercellular adhesion and that -cat is also involved in invasion and metastasis. In particular, reduction of -cat expression is more correlated with invasive phenotype and lymph node metastasis than E-cad expression in human esophageal cancer.

¹ This work was supported in part by Grant-in-Aid for Cancer Research 04454333 from the Ministry of Education, Science and Culture, Japan.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/ 6/93. Accepted 10/26/93.

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