Proliferating cell nuclear antigen expression at the invasive tumor margin predicts malignant potential of colorectal carcinomas

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Abstract
Background. Proliferative activity may be a useful measure of malignant potential for a variety of tumors. Colorectal carcinomas contain multiple cell populations with different biologic properties. The invasive tumor margin is thought to represent the area with the highest metastatic potential. Methods. Cell proliferation at the invasive tumor margin of 49 specimens of advanced colorectal carcinoma was assessed by immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and compared with clinicopathologic findings. Results. Colorectal carcinomas showed a wide range of PCNA labeling indexes (LI), reflecting variation in proliferative activity. The PCNA LI of tumors showing venous invasion (mean, 51.7% ± 16.2%) was significantly higher than that of tumors without venous invasion (mean, 36.7% ± 18.2%; P < 0.01). A strong association was observed between the PCNA LI and the metastatic potential of colorectal carcinoma; the PCNA LI of tumors showing lymph node metastasis (mean, 50.5% ± 17%) was significantly higher than that of tumors without nodal involvement (mean, 39.8% ± 18.5%; P < 0.05). In addition, the PCNA LI of tumors metastatic to liver (mean, 55.2% ± 15.7%) was significantly higher than that of tumors without liver metastasis (mean, 41.0% ± 17.6%; P < 0.01). Correlation with histologic features at the invasive tumor margin showed that a higher PCNA LI was associated with less differentiated tumors (P < 0.05). Conclusion. Evaluation of the PCNA LI at the invasive tumor margin may help identify colorectal carcinomas that have a higher malignant potential.