Hironobu Toyoyama

Expression of thrombomodulin in squamous cell carcinoma of the lung: its relationship to lymph node metastasis and prognosis of the patients☆

Thrombomodulin (TM) is a type of thrombin receptor that was identified originally on the endothelium and acts as a natural anticoagulant through converting thrombin from a procoagulant protease to an anticoagulant. We reported previously that TM was also expressed in the squamous epithelium mainly at the intercellular bridges. In this study, we examined TM expression in the primary lesions of 81 patients with squamous cell carcinomas (SCCs) of the lung and in the lymph node metastatic lesions of 39 patients using immunohistochemical methods. The carcinoma tissues expressed TM mainly at the cell-cell boundaries and also in the cytoplasm. When TM expression was compared between the primary and metastatic lesions in the 39 patients who had lymph node metastasis, 26 (67%) showed decreased TM expression, 13 (33%) showed no change, and none (0%) showed an increase in the metastatic lesions. Wilcoxons signed-rank test indicated that tumor cells that were positive for TM expression were significantly rarer in the metastatic lesions than in the primary tumors (P < 0.0001). The present study also showed that the patients with TM-negative expression in the primary tumors showed significantly poorer survival than those with TM-positive expression, mainly due to distant metastases of poorly-differentiated SCCs with negative TM expression in the primary tumors. These results indicate that the reduction of TM expression seems to play an important role in the metastatic process of lung SCCs.

The expression of cadherin-catenin complex in association with the clinicopathologic features of early gastric cancer.

Although impaired expression of E-cadherin (E-cad) is frequently observed in tumors with aggressive histopathologic characteristics, the correlation between α-catenin (α-cat) expression and the clinicopathologic features of early gastric cancer have not been fully examined. In this study, we evaluated the expression of E-cad and α-cat by early gastric carcinomas, and examined the relationships between this expression and various clinicopathologic characteristics. A total of 69 specimens obtained from surgery were studied by immunohistochemistry. Reduced expression of E-cad and α-cat were found in 53.6% and 65.2% of the tumors, respectively, and a significant correlation was observed between the decreased expression of E-cad or α-cat and tumor histology, the quantity of stroma, and the infiltration pattern of the tumor. The reduced expression of α-cat correlated more strongly with these features than E-cadherin expression. Furthermore, α-cat expression was also related to the lymph node metastasis of tumors. The expression of E-cad or α-cat in the primary tumor was consistent with the expression of tumor cells that invaded the lymphatic vessels, but discordant with staining in the metastasized lymph nodes. In some cases, as the tumor invaded deeper, the expression of E-cad or α-cat changed from preserved to reduced. Our observations suggest that the reduced expression of E-cad or α-cat may be involved in the initial steps leading to the invasion and metastasis of early gastric cancer.

Abnormal expression of β- and γ-catenins in early gastric cancer

BackgroundE-cadherin and α-catenin are closely correlated with the clinicopathology of advanced gastric cancer, but little is known about the functions and mechanisms of β- and γ-catenins. In this study, we evaluated the expression of β- and γ-catenins in early gastric cancer.MethodsSixty-nine specimens, obtained by surgery from patients with early gastric cancer, were studied by immunohistochemistry, using monoclonal anti-β- and anti-γ-catenin antibodies.ResultsReduced expression of β- and γ-catenins was found in 28% and 39% of early gastric cancer specimens, respectively. The reduction in the expression of β-catenin was related to patient age and tumor size, while the reduction in γ-catenin expression was related to the histologic type and infiltration pattern of the tumor. A significant correlation was observed between the expression of β-catenin and that of γ-catenin. Tumors in which simultaneous staining showed heterogenous expression of β- and γ-catenins had a higher rate of lymph node metastasis.ConclusionsChanges in the quantity of β- or γ-catenin act as factors that take part in some process that indirectly affects cell-to-cell adhesion and detachment. Combined examination of β- and γ-catenins may be helpful in predicting the outcome for patients with early gastric cancer.

A Case of Long Surviving Lung Cancer with Concomitant Multiple Intrapulmonary Metastasis.

症例は62歳男性. 微熱., 血痰を主訴に来院した. 胸部X線写真, CTで右肺門部の腫瘤影と下肺野に多発性の結節影を指摘された. 縦隔リンパ節郭清を伴う右中下葉切除が施行され, 主病巣と同一肺葉内に多数の肺内転移をともないp-T4N0M0, Stage IIIB中分化型の扁平上皮癌と診断された. 本症例の同一肺葉内の多発肺内転移様式として, 従来より提唱されている肺動脈を介しての肺内転移のみならず経気道性の播種性散布も示唆された. その根拠は主病巣が右B8とB9+10分岐の気管支壁より発生しB8とB9+10気管支内腔へそれぞれ進展しており, 末梢S8, 9の2区域内に多発する12個 (最小2×2mm, 最大14×7mm) の肺内転移巣のうち数ヶ所に末梢気管支内腔からの気管支壁への腫瘍の浸潤が認められたことである. 本症例は術後12年という長期にわたり生存した.