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 canc er (8 carcinoma-in-adenoma cases and 17 invasive cancer cases) of huma n colon. Proliferative activity by PCNA index and the activity of prot ein synthesis by AgNORs were also estimated for all cases as the suppo rting markers of malignancy. In all border-line cases, the following f indings were obtained: (1), the degree of DNA-instability as revealed by immunohistochemical staining with anti-single-stranded DNA antiseru m after acid hydrolysis was increased in border-line adenoma to the le vel of invasive overt cancer, indicating its malignancy with marked DN A-instability; (2), reflecting the malignant character, abnormal mitos is and single cell necrosis were usually observed in all border-line a denomas by fluorescent Feulgen staining, indicating the DNA alteration s; (3), not only the parenchymal but also the stromal PCNA indices wer e 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 wit h those in benign adenoma, and these showed further increases with the progression of malignancy to the invasive overt cancer. These finding s indicate that border-line adenoma of human colon has already maligna nt character at the early progression stage, although no apparent epit helial atypia, or destructive invasion, is taking place.