Thrombomodulin as a Marker for Vascular Tumors: <i>Comparative Study with Factor VIII and</i> Ulex europaeus <i>I Lectin</i>

Yonezawa, Suguru; Maruyama, Ikuro; Sakae, Kiyohiro; Igata, Akihiro; Majerus, Philip W.; Satô, Eiichi

doi:10.1093/ajcp/88.4.405

Cited by 73 publications

(29 citation statements)

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“…It would seem, therefore, that similar to squamous and other epithelial carcinomas, neoplastic TM expression is protective in primary colorectal adenocarcinomas. However, unlike squamous cells where TM is expressed under normal conditions (Mizutani et al, 1996;Yonezawa et al, 1987) only 7.8% of normal colonic epithelial cells expressed TM. Therefore, while colonic epithelial cells do not produce TM under normal conditions, they must be phenotypically capable of doing so in certain environments.…”

Section: Discussionmentioning

confidence: 90%

Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival

et al. 2006

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Thrombomodulin (TM) is an endothelial receptor that exhibits anticoagulant, antifibrinolytic and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. In this study, the expression and significance of TM was examined in primary colorectal cancer and its prognostic implications explored. TM immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections, from primary lesions of 200 patients with colorectal carcinoma. Institutional Ethical approval was granted and clinical data retrieved from patients' records. All normal colonic tissue expressed TM on endothelial cells. TM tumour cell expression was demonstrated in 53 (26.5%) cases and 147 (73.5%) showed no neoplastic cell staining. On univariate and multivariate analysis TM expression on tumour cells correlated significantly with tumour stage, differentiation, Jass score and 5 year survival. TM expression decreases as overall stage and tumour size increase (P ¼ 0.03). In all, 91% TM positive tumours were well differentiated and 85% of TM negative tumours were poorly differentiated (Po0.01). Five year survival rates of patients with positive and negative TM expression were 71 and 41%, respectively. Survival rate was poorer in those patients who were TM negative compared with those who were positive (Po0.01). A total of 101 (50.5%) of the cases were node negative. In this group, 5 year survival rates of patients with positive and negative TM expression were 87.5 and 37.8%, respectively, demonstrating a poorer survival rate for those who are node negative and TM negative at the time of surgery (Po0.001). This study demonstrates that loss of TM is a key indicator in tumour biology and prognosis.

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Section: Discussionmentioning

confidence: 90%

Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival

et al. 2006

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“…Immunohistochemical staining was performed using an ABC kit (Vector Laboratories, Burlingame, CA), as described previously (17,28). Briefly, paraffinembedded tissue samples were reacted with each antibody, as indicated in the presence of 1% BSA for 12 hours at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…Activated protein C exerts additional anticoagulant effects by inactivating coagulant cofactors Va and VIIIa (7,8,12). Thrombomodulin is also expressed at extravascular sites, such as in syncytiotrophoblasts in the placenta, in the epithelial tissues of gingiva, in the skin, lungs and digestive organs, and in the synovial lining cells (15)(16)(17)(18)(19). However, the functional role of thrombomodulin in the extra-vascular space, apart from the possible limitation of thrombin generation at these sites, remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

The Antimetastatic Role of Thrombomodulin Expression in Islet Cell-Derived Tumors and Its Diagnostic Value

Iino¹,

Abeyama²,

Kikuchi³

et al. 2004

Clinical Cancer Research

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Islet cell tumors, endocrine neoplasm arising from pancreatic islets of Langerhans, are histologically difficult to diagnose as benign or malignant. Molecular markers are associated with the clinical characteristics that most of insulinoma are usually benign tumors, whereas other islet cell tumors are malignant but have not been identified. In this context, we newly found that an endothelial anticoagulant thrombomodulin was expressed in the normal islet ␤ cells and insulinoma, but not of other islet components or noninsulinoma islet cell tumors. Clinically, all of the subjects (n ‫؍‬ 15) of the insulinoma group showed no metastasis together with thrombomodulin expression in the lesions, whereas the other islet cell tumor groups showed a high incidence of metastasis (82%) and a low expression rate of thrombomodulin (6%). To examine the functional role of thrombomodulin, especially regarding the clinical characteristics of islet cell tumors, we tested the effect of exogenous thrombomodulin overexpression on cell adhesiveness and proliferation using MIN6 insulinoma cell line. In cell-based experiments, thrombomodulin overexpression reduced cell proliferation and enhanced Ca 2؉ -independent cell aggregation, possibly through direct interaction with neural cell adhesion molecule. Taken together, these results are suggesting that thrombomodulin may act as antimetastatic molecule of insulinomas. In addition, thrombomodulin is a clinically useful molecular marker not only for identifying ␤-cell-origin islet cell tumors (i.e., insulinomas) but also for predicting disease prognosis of islet cell tumors.

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“…Immunocytochemical staining was performed by an immunoperoxidase method using ABC complex as described previously [15,16]. (Fig.3).…”

Section: Cultured Cellsmentioning

confidence: 99%

“…At those sites, TM plays an important role in an anticoagulation system. In our previous study, we found that TM was expressed also in the squamous epithelium of epidermis, except in the basal layer cells, mainly at the intercellular bridges [16]. Our recent study [14] revealed positive TM expression in esophageal squamous cell carcinoma (SCC), and an inverse correlation of the TM expression with the lymph node metastasis.…”

Section: Introductionmentioning

confidence: 99%

Expression of Thrombomodulin in Esophageal Squamous Cell Carcinoma Cell Lines.

Yonezawa¹,

Tezuka²,

Matsushita³

et al. 1996

Acta Histochem. Cytochem

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Thrombomodulin as a Marker for Vascular Tumors: Comparative Study with Factor VIII and Ulex europaeus I Lectin

Cited by 73 publications

References 0 publications

Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival

Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival

The Antimetastatic Role of Thrombomodulin Expression in Islet Cell-Derived Tumors and Its Diagnostic Value

Expression of Thrombomodulin in Esophageal Squamous Cell Carcinoma Cell Lines.

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