Clinicopathologic and genetic analysis on histogenesis and development of colorectal carcinoma

(1)MUC1表达、E-cadherin表达降低、MVC增高和浸润深度Ki-67阳性指数增高对晚期结直肠癌预后有重要意义。(2)组织蛋白酶D在癌细胞中的表达模式与肿瘤的组织分化和转移潜能显著相关。相反，基质细胞中的组织蛋白酶D表达可能参与癌组织中发生的基质反应，并可能促进癌细胞侵袭和转移。(3)最深浸润部位的微血管计数（MVC）是粘膜下结直肠癌（CRC）淋巴结转移的独立危险因素。低MVC（<40）和粘膜下浸润达1500 μ m的病变无淋巴结转移，无论组织学分级如何。(4)Glut1在最深肿瘤浸润部位的表达是晚期CRC恶性潜能较高和预后较差的重要预测因子，比除淋巴结转移外的其他常用临床病理学指标更有用。此外，Glut1和Ki-67表达的联合分析可能更有助于预测晚期CRC根治性手术患者的预后。(5)VEGF-C在肿瘤最深浸润部位的表达是晚期结直肠癌恶性潜能高和预后差的重要预测因子，并且与血管生成密切相关。我们的研究结果提示MVD和VEGF-C在结直肠癌的血管生成和淋巴管生成中起重要作用。(6)在溃疡性结肠炎（UC）相关癌中，p53过表达是肿瘤形成的有用标志物，而pS2显然在癌从异型增生发展的点附近参与。MUC1的表达可能是一个较晚的事件在肿瘤转化过程中的UC相关癌比它是在散发性腺瘤癌序列。

(1) MUC1 expression, E-cadherin reduced expression, a high MVC, and a high Ki-67 LI at the site of deepest tumor invasion are significant for advanced colorectal cancer prognosis.(2) Cathepsin D expression patterns in cancer cells significantly correlates with histologic differentiation and metastatic potential of tumors. In contrast, cathepsin D expression in stromal cells may be involved in the stromal reactions occurring in cancer tissue and may facilitate cancer cell invasion and metastasis.(3) Microvessel count (MVC) at the site of deepest penetration was an independent risk factor for lymph node metastasis in submucosal colorectal carcinoma (CRC). Lesions with low MVC (<40) and submucosal invasion up to 1500 μm had no lymph node metastasis, regardless of histologic grade.(4) Glut1 expression at the site of deepest tumor invasion is an important predictor of a higher malignant potential and poorer prognosis of advanced CRC, and more useful than other clinicopathologic factors commonly used, except for lymph node metastasis. Furthermore, combined analysis of Glut1 and Ki-67 expression can be more useful in predicting the prognosis of patients who have undergone curative surgery for advanced CRC.(5) VEGF-C expression at the site of deepest tumor invasion is an important predictor of a higher malignant potential and poorer prognosis of advanced CRC and is closely related to angiogenesis. Our study results suggest that MVD and VEGF-C may play an important role in angiogenesis and lymphangiogenesis in CRC.(6) In ulcerative colitis (UC)-associated carcinoma, p53 overexpression is a useful marker of neoplasia, whereas, pS2 apparently becomes involved near the point where carcinoma develops from dysplasia. MUC1 expression may be an later event in the process of neoplastic transformation in UC-associated carcinoma than it is in the sporadic adenoma-carcinoma sequence.