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According to the histologic features at the deepest level of tumor invasion (the tumor apex), we classified colorectal carcinomas as follows: well differentiated (W), moderately differentiated (M), and mucinous (Muc). By assessing its glandular configuration and cellular arrangement, the M type was further subdivided in to two different groups: moderately well differentiated (Mw) and moderately poorly differentiated (Mp) carcinomas. In our sample there were 56 W, 53 Mw, 20 Mp and 13 Muc tumors. The malignant potential of each tumor was evaluated by examining for the presence or absence of lymphatic invasion, venous invasion, lymph node metastases and liver metastases. In comparison with the other tumors, the Mp tumors proved to harbor the highest malignant potential, exhibiting a higher incidence of lymphatic invasion (95%, 19/20 of the cases), venous invasion (75%, 15/20 of the cases), lymph node metastases (80%, 16/20 of the cases), and liver metastases (40%, 8/20 of the cases). Colorectal carcinomas are composed of multiple cell populations with different biological and malignant properties, and through the histologic sub-classification we could identify that Mp tumors have the highest potential to invade normal tissue and metastasize.

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.

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The potential of flat-elevated colorectal adenomas to undergo rapid malignant transformation and progression to invasive carcinoma is still under discussion. Therefore, a total of 130 colorectal neoplastic lesions ≥ 1 cm in diameter were examined after endoscopic or surgical resection. Lesions were macroscopically classified into three categories: (1) flat elevation (22 lesions), superficially elevated lesion with a smooth surface; (2) granular laterally spreading tumor (GLST; 26 lesions), laterally spreading aggregates of nodules forming a lesion with granular surface, and (3) polypoid (82 lesions), pedunculated, sub-pedunculated and sessile polyps. The adenomatous component showed a tubulovillous architecture in 9/26 (35%) of GLST and 18/82 (22%) of polypoid lesions, however none of the flat-elevated lesions had a villous component (p < 0.01; p < 0.05). Carcinoma was present in 17/22 (77%) flat elevations, 37/82 (45%) polypoid lesions and 11/26 (42%) GLST (p < 0.05). None of the carcinomas arising in GLST and only 1/37 (3%) of those developing in polypoid lesions were invasive carcinomas, but 4/17 (24%) carcinomas arising in flat elevations showed submucosal invasion. Moreover, while all 5 noncancerous flat elevations showed severe atypia, 17/82 (21%) polypoid lesions and 5/26 (19%) GLST showed moderate atypia. In conclusion, flat-elevated colorectal neoplasms have a high malignant potential and the role of these lesions as precursors ofcolorectal carcinomas deserves greater emphasis.

Magnified virtual chromoendoscopy is as accurate as indigo carmine magnified chromoendoscopy in distinguishing between neoplastic from non-neoplastic small colorectal lesions.