Combined expression of urokinase-type plasminogen activator and proliferating cell nuclear antigen at the deepest invasive portion correlates with colorectal cancer prognosis.

To examine the relationship among the expression of urokinase-type plasminogen activator (u-PA), invasive/metastatic potential and prognosis of colorectal cancer (CRC), 58 patients with surgically resected advanced CRC were studied. u-PA expression and proliferating cell nuclear antigen labeling index (PCNA-LI) at the deepest invasive portion were examined immunohistochemically. u-PA expression was detected in 37 (63.8%) of 58 lesions. Lesions with liver metastasis showed a significantly (p < 0.01) higher incidence of u-PA expression than those without liver metastasis. Dukes staging also revealed a significant correlation with u-PA expression. The combination of u-PA expression and elevated PCNA-LI at the deepest invasive portion correlated significantly with prognosis. These results indicate that u-PA expression is an important predictor of CRC development and liver metastasis. Furthermore, combined analysis of u-PA expression and PCNA-LI at the deepest invasive portion is very useful in predicting CRC prognosis.

Endoscopic treatment of submucosal invasive colorectal carcinoma with special reference to risk factors for lymph node metastasis.

A clinicopathological analysis of the risk factors for lymph node metastasis was performed in 177 patients with submucosal invasive colorectal carcinoma (CRC). The submucosal deepest invasive portion was histologically subclassified as well (W), moderately (M), or poorly (Por) differentiated. M type was further subdivided into moderately-well (Mw) and moderately-poorly (Mp) differentiated. The pattern of tumor growth was classified as polypoid growth (PG) and non-polypoid growth (NPG). Lymph node metastasis was detected in 21 (12%) of the 177 patients. Macroscopically, type IIc and IIa + IIc lesions showed a significantly higher incidence of lymph node metastasis (44% and 30%) than type IIa and I (4% and 8%). Regarding the histologic subclassification, Por and Mp lesions showed a significantly higher incidence of lymph node metastasis (67% and 37%) than W and Mw lesions (4% and 14%). NPG tumors showed a significantly higher incidence of lymph node metastasis (29%) than PG tumors (7%). The depth of submucosal invasion and lymphatic invasion (ly) were also significantly correlated with the incidence of lymph node metastasis (submucosal scanty (sm-s) invasion 4%, massive invasion 20%; ly(+) 23%, ly(-) 5%). None of the lesions with both sm-s invasion and of W or Mw type showed lymph node metastasis. These results indicate that submucosal invasive CRC with both sm-s invasion and of W or Mw type, which shows no ly, is the appropriate indication for endoscopic curative treatment.

[Assessment for development of superficial colorectal neoplasm--endoscopic and clinicopathologic analysis of 149 submucosal invasive carcinomas].

We performed the endoscopic and clinicopathologic analysis for the development of superficial colorectal carcinoma, using 149 submucosal (sm) invasive colorectal carcinomas. It was observed that superficial colorectal carcinomas had a tendency to rise by their sm massive invasion. In this study, we judged that the sm colorectal carcinomas originated from superficial colorectal carcinoma were 37 (25%) of 149 lesions, and their distribution in the colon and rectum was similar to that of advanced colorectal carcinomas, although the lesions originated from non-superficial (polypoid) colorectal carcinoma did not show so tendency. On the other hand, sm colorectal carcinomas originated from superficial colorectal carcinoma contained the evident adenomatous components in 7 (19%) of 37 lesions and had significantly higher incidence of lymph node metastasis than those originated from non-superficial (polypoid) carcinoma. These results suspected the facts as follows; 1) Superficial early colorectal carcinoma may be compatible as the origin to advanced colorectal carcinoma and has higher malignant potential than non-superficial early carcinoma. 2) Superficial colorectal carcinoma might also have the route of the development of "adenoma-carcinoma sequence", as well as "de novo" histogenesis.

Proliferating cell nuclear antigen expression correlates with the metastatic potential of submucosal invasive colorectal carcinoma.

To examine the malignant potential of submucosal invasive colorectal carcinoma, the relationship between proliferating cell nuclear antigen (PCNA) expression and clinicopathologic risk factors for lymph node metastasis was studied in 149 patients with submucosal invasive colorectal carcinoma. The depth of submucosal invasion was classified as scanty or massive. Histologic subclassification at the submucosal deepest invasive portion was done as follows: well differentiated (W), moderately well differentiated (Mw), moderately poorly differentiated (Mp) or poorly differentiated (Por). Tumor growth was divided into polypoid growth and nonpolypoid growth. The PCNA expression (labeling index, LI) was examined at the submucosal deepest invasive portion. The PCNA-LI of tumors showing lymph node metastasis (mean, 56.5 +/- 19.0%) was significantly higher than that of tumors without lymph node metastasis (mean, 41.5 +/- 19.3%; p < 0.01). The PCNA-LI of Mp tumors (mean, 57.7 +/- 16.5%) was significantly higher than that of W (mean, 38.5 +/- 19.0%; p < 0.05) and Mw (mean, 43.7 +/- 19.1%; p < 0.05) tumors. The PCNA-LI of tumors without adenomatous features (mean, 47.9 +/- 20.5%) was significantly higher than that of tumors with such features (mean, 37.1 +/- 17.1%; p < 0.05). The PCNA-LI was not correlated with other risk factors for lymph node metastasis, such as lymphatic invasion, depth of submucosal invasion, macroscopic type, and growth pattern. These results indicate that the PCNA-LI may be useful marker for predicting the potential metastases to lymph nodes in submucosal invasive colorectal carcinoma, while the proliferative activity of cancer cells correlates with the degree of the differentiation in the area of deepest invasion.