EXPRESSION AND LOCALIZATION OF THROMBOMODULIN IN PRENEOPLASTIC BRONCHIAL LESIONS AND IN LUNG-CANCER

Thrombomodulin (TM) is an endothelial surface glycoprotein that acts a s a natural anticoagulant. It inhibits thrombin and accelerates the ac tivation of the anticoagulant protein C. TM has been detected in derma l keratinocytes, where it is associated with terminal differentiation. It can also be detected in various types of squamous malignant neopla sms and in malignancies of endothelial and mesothelial origin, such as Kaposi's sarcoma or malignant mesothelioma, but is absent in pulmonar y adenocarcinomas (AC). Seventy-two lung tumour specimens [33 squamous cell carcinomas (SQCC), 23 AC, 1 large cell carcinoma, 8 small cell l ung cancers (SCLC) and 7 multidifferentiated tumours (MT)] were analys ed immunohistochemically by staining with an anti-TM antibody in order to assess TM expression. All of the SQCC stained positively for TM. I II contrast, only 9 AC and 4 MT and none of the SCLC showed positive a nti-TM staining. Seven hyperplastic bronchial epithelial specimens and eight preneoplastic bronchial lesions (five cases of moderate dysplas ia, two cases of severe dysplasia and one case of carcinoma in situ) w ere used as controls. Normal or hyperplastic areas of bronchial epithe lium revealed no positive reaction. However, a distinct positive anti- TM staining pattern related to the degree of keratiniziation of dyspla stic lesions was seen. The present results suggest that anti-TM immuno staining is a useful marker for squamous cell carcinoma in the differe ntial diagnosis of pulmonary carcinoma, also indicating keratinocyte d ifferentiation in dysplastic bronchial epithelium.