Early progression stage of malignancy of human colon border-line adenoma as revealed by immunohistochemical demonstration of increased DNA-instability.

The degree of DNA-instability was used as the marker of malignancy and applied to adenoma (7 benign cases and 17 border-line cases) and cancer (8 carcinoma-in-adenoma cases and 17 invasive cancer cases) of human colon. Proliferative activity by PCNA index and the activity of protein synthesis by AgNORs were also estimated for all cases as the supporting markers of malignancy. In all border-line cases, the following findings were obtained: (1), the degree of DNA-instability as revealed by immunohistochemical staining with anti-single-stranded DNA antiserum after acid hydrolysis was increased in border-line adenoma to the level of invasive overt cancer, indicating its malignancy with marked DNA-instability; (2), reflecting the malignant character, abnormal mitosis and single cell necrosis were usually observed in all border-line adenomas by fluorescent Feulgen staining, indicating the DNA alterations; (3), not only the parenchymal but also the stromal PCNA indices were statistically larger in border-line adenoma than in benign adenoma, indicating the "stromal activation" in malignancy; (4), the volumes of AgNORs were much increased in border-line adenoma in comparison with those in benign adenoma, and these showed further increases with the progression of malignancy to the invasive overt cancer. These findings indicate that border-line adenoma of human colon has already malignant character at the early progression stage, although no apparent epithelial atypia, or destructive invasion, is taking place.