CELLULAR-LOCALIZATION OF THROMBOMODULIN IN HUMAN EPITHELIUM AND SQUAMOUS MALIGNANCIES

Thrombomodulin is a cell surface glycoprotein that functions as an ant icoagulant. Although initially identified on endothelial cells, thromb omodulin is also expressed by other vascular cells, by mesothelial cel ls, and by, epidermal keratinocytes, To determine whether thrombomodul in is expressed by epithelial cells in locations other than skin, we c onducted a survey, of thrombomodulin protein and mRNA in human epithel ium Thrombomodulin protein was detected by immunohistochemistry in all samples containing stratified squamous epithelium, including oral muc osa, larynx, esophagus, uterine ectocervix, and vagina In these tissue s, thrombomodulin staining localized to the suprabasal layer, with min imal staining observed in the basal or superficial layers of epitheliu m. Thrombomodulin was not detected in cuboidal, simple columnar, or ps eudostratified columnar epithelium and was detected variably in transi tional epithelium Thrombomodulin staining was also observed in 21 of 2 6 cases of invasive squamous cell carcinoma and in several examples of squamous carcinoma-in-situ and squamous metaplasia. Expression of thr ombomodulin mRNA was confirmed by in situ hybridization in both normal and malignant squamous epithelium. Full-length, functionally active t hrombomodulin was demonstrated in cultured squamous epithelial cells T hese data demonstrate that thrombomodulin expression correlates with t he squamous phenotype and suggest that hemostasis is regulated by comp artmentalization of procoagulant and anticoagulant epithelial proteins .