Prognostic value and clinicopathological correlation of thrombomodulin in squamous cell carcinoma of the human lung.

Aggregation of host platelets by circulating tumor cells is believed to play an important role in the metastatic process. Because thrombomodulin (TM) is one of the major mediators of the activation of the anticoagulant protein C by thrombin, we examined 136 primary tumor tissues and 45 metastatic lymph node tissues of lung squamous cell carcinomas for TM expression using immunohistochemical methods. The number of tumors with positive TM staining was less in metastatic tumors (44%) than in primary tumors (74%) (P < 0.01). Of various clinicopathological factors, better differentiation and lower N stage were significantly associated with TM expression. A loss of TM expression was associated with a shortened survival in 113 patients who underwent complete resection of the lung tumor (P < 0.01). In this group, TM expression and tumor-node-metastasis staging were independent significant determinants for survival, determined using Cox's multivariate survival analysis. Since TM is apparently associated with tumor progression and differentiation, this correlation may serve as a prognostic indicator in squamous cell carcinoma of the lung.

[1]  S. Natsugoe,et al.  Expression of thrombomodulin in esophageal squamous cell carcinoma and its relationship to lymph node metastasis. , 1995, Cancer research.

[2]  T. Raife,et al.  Cellular localization of thrombomodulin in human epithelium and squamous malignancies. , 1995, The American journal of pathology.

[3]  W. Jiang,et al.  Molecular and cellular basis of cancer invasion and metastasis: Implications for treatment , 1994, The British journal of surgery.

[4]  T. Raife,et al.  Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation. , 1994, The Journal of clinical investigation.

[5]  J. Eidt,et al.  Thrombomodulin activity and localization. , 1993, The International journal of developmental biology.

[6]  J. Sheehan,et al.  Structure-function relationships of the thrombin-thrombomodulin interaction. , 1993, Haemostasis.

[7]  N. Ordóñez,et al.  Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma. , 1992, The American journal of pathology.

[8]  H. Yamaguchi,et al.  Identification of fetomodulin, a surface marker protein of fetal development, as thrombomodulin by gene cloning and functional assays. , 1990, Developmental biology.

[9]  B. Zetter,et al.  Tumor interactions with the vasculature: angiogenesis and tumor metastasis. , 1990, Biochimica et biophysica acta.

[10]  William,et al.  Structure and function of thrombomodulin: a natural anticoagulant. , 1990, Blood.

[11]  R. Cook,et al.  Cloning of GMP-140, a granule membrane protein of platelets and endothelium: Sequence similarity to proteins involved in cell adhesion and inflammation , 1989, Cell.

[12]  I. Maruyama,et al.  Endothelium and thrombomodulin: expression and distribution of thrombomodulin on altered endothelium and neoplastic syncytiotrophoblast. , 1989, Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society.

[13]  I. Maruyama,et al.  Immunohistochemical localization of thrombomodulin in chorionic diseases of the uterus and choriocarcinoma of the stomach. A comparative study with the distribution of human chorionic gonadotropin , 1988, Cancer.

[14]  T. E. Petersen,et al.  The amino‐terminal domain of thrombomodulin and pancreatic stone protein are homologous with lectins , 1988, FEBS letters.

[15]  C. Mountain,et al.  A new international staging system for lung cancer. , 1987, Chest.

[16]  H. Yamaguchi,et al.  Fetomodulin: marker surface protein of fetal development which is modulatable by cyclic AMP. , 1987, Developmental biology.

[17]  D. Stern,et al.  Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Esmon,et al.  Isolation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C. , 1982, The Journal of biological chemistry.

[19]  J. Guesdon,et al.  The use of avidin-biotin interaction in immunoenzymatic techniques. , 1979, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[20]  M. Pike,et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. , 1977, British Journal of Cancer.

[21]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[22]  J. van Lunzen,et al.  Vascular origin of Kaposi's sarcoma. Expression of leukocyte adhesion molecule-1, thrombomodulin, and tissue factor. , 1994, The American journal of pathology.

[23]  田村 厚久.  Detection of thrombomodulin in human lung cancer cells , 1994 .

[24]  C. Esmon,et al.  Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture. , 1989, Blood.