DNA INDEX SHIFT WITH DISEASE PROGRESSION IN COLORECTAL ADENOCARCINOMA- A MORPHOLOGICAL AND FLOW CYTOMETRIC STUDY

DNA index (DI) values seen in 86 sporadic colorectal adenocarcinomas w ere related to clinical, morphological, and disease progression featur es. DI, whose overall distribution was bimodal with peaks in the diplo id and from hypotriploid to tetraploid ranges, tvas related to patholo gical lymph node staging (pN), staging, lymphoid reaction, and tubular configuration. With increasing severity in pathological features, an irregular shift in DI class prevalence was seen, with no steady increa se from diploidy to higher degrees of aneuploidy. All UICC stage I tum ors (13% of total) were aneuploid, 50% being hypertriploid; diploidy ( 35%) and hypertriploidy (22%) prevailed in stage II carcinomas (41% of total), diploidy (35%) and hypotriploidy (30%) in stage III (30% of t otal), and triploidy (33%) in stage TV (15% of total). Amongst feature s related to stage (lymphoid reaction, depth of neoplastic embolizatio n, grading, tubular configuration, and polymorphism), few were associa ted with IPI, and none influenced DI shift and class prevalence throug h the stages. The biological capabilities of colorectal adenocarcinoma in relation to stage are expressed by certain aneuploid DI classes (h ypertriploidy: absence of extracolonic spread; hypotriploidy: lymph no de metastases; triploidy: distant metastases). Diploidy is unrelated t o criteria defining stage above I and predicts 50% of cases with devel opment of metachronous metastases. Irregular DI class shift through th e stages may be attributable to different pathways of cancerogenesis a nd disease progression in diploid versus aneuploid carcinomas. Alterna tively, assuming that the diploid fraction in aneuploid tumors contain s neoplastic cells, pure diploid carcinomas represent the selection of a vital clone that may give rise to a further mixed population whose aneuploid DI is different and best fitted to express the biological ca pabilities of that given stage. Copyright (C) 1998 by W.B. Saunders Co mpany.