Search

In this prospective study, the independent prognostic value of DNA ploidy in combination with the major clinico-pathological characteristics (histological grade, nodal status, tumor size, estrogen and progesterone receptor status, number of tumors, multicentricity, lympho-vascular infiltration) was evaluated in a series of 399 breast-cancer patients. The mean follow-up time was 4.5 years. The DNA content was measured using image cytometry on fresh tumor samples. The overall survival of tetraploid and slowly proliferating diploid cases was significantly different compared with that of aneuploid and rapidly proliferating diploid cases (p = 0.0002). Thus, DNA ploidy combined with S-phase estimate (DNA histogram type) appeared to be good prognostic factors. In a multivariate survival analysis, DNA histogram type was not an independent prognostic factor unless the histological grade was excluded. This effect of DNA histogram type on survival was also observed among patients with grade-I or -II tumors and patients with small tumors. In conclusion, DNA histogram type was a valuable prognostic factor in univariate analysis, and provided independent complementary information for patients considered at low or intermediate risk by classical pathological findings.

DNA ploidy status of tumour cells is becoming a part of patient's record, because it brings an objective assessment of diagnostic and prognostic significance. DNA ploidy status in diagnosis--DNA ploidy status of some tumour types can be used as an adjunct to cytologic or histologic examination and provide an additional diagnostic information. For example, small cell lung carcinoma cells may be difficult to differentiate from cells of other benign neuroendocrine tumours. By computing the DNA malignancy grade, as defined by Bocking A. et al., it was possible to distinguish levels of malignancy among neuroendocrine tumours. Thus we were able to demonstrate that typical carcinoids may be differentiated from small cell carcinomas and atypical carcinoids. DNA ploidy status in prognosis--A large number of studies strongly support a correlation between DNA ploidy patterns and clinical course of malignant tumours. However, the prognostic value of DNA ploidy status has to be evaluated in relation to conventional clinico-pathologic characteristics, by multivariate analysis in order to demonstrate its independent contribution. For example, we demonstrated, in a prospective study of 211 colorectal adenocarcinomas, that ploidy status was an independent predictor of prognosis only in the early stages of the disease (Dukes' A, B, C), but not when advanced stages-(Dukes' D) were considered. In conclusion, DNA ploidy status may be used as an important objective parameter either in diagnosis or in prognosis, complementary to the traditional clinico-pathological characteristics.

In a prospective study, the DNA content of Feulgen-stained nuclei obtained from fresh samples of 211 colorectal adenocarcinomas was evaluated by means of image analysis. The DNA histogram classification took into account aneuploidy and S-phase fraction for diploid cases. No significant relationship was found between ploidy and sex, age, preoperative carcinoembryonic antigen (CEA), size of the tumor, histologic differentiation, or Dukes' stage. Aneuploidy was more frequently encountered in distal tumors. Preoperative CEA, histologic differentiation, Dukes' stage, and ploidy were individually associated with overall survival. In Dukes' A, B, and C tumors, patients with normal and elevated CEA had no significant difference in overall survival. A relationship was apparent between disease-free survival and site, histologic differentiation, Dukes' stage, and ploidy. Multivariate overall survival analysis did not reveal independent prognostic significance of ploidy when all Dukes' stages were considered. In contrast, Dukes' stage, differentiation, and ploidy were good indicators of higher risk of colorectal cancer-related death in patients undergoing curative surgery. Dukes' stage and ploidy were also indicators for recurrence. Thus, routine histopathologic characteristics should be used in combination with quantitative cytologic features for the definition of a relevant prognostic index in colorectal cancer.

The analysis of ploidy provides valuable information allowing a more precise diagnosis, a more dependable prognostic and the choice of appropriate therapy. With ploidy analysis one can assess the aggressiveness of a given tumor. Aneuploidy of tumors clearly indicates a significantly lower patient survival index. Ploidy analysis of tissue sections yields a clear overall indication of the proportion of cells exhibiting hyperploidy within the tumor mass. The application of this approach is amenable to diverse types of tumors including colo-rectal neoplasias. Additionally, it provides a correlation with the histological presentation of each tumor. The study includes DNA ploidy analysis of 212 patients with primary adenocarcinoma. Sixty-four of the cases examined had follow-ups of a least 2 years. Eighteen of this group had diploid non-proliferating tumors, of which 2 (11%) subsequently died. Nineteen of the 64 had proliferating diploid tumors, 11 (58%) of whom died within the follow-up periods. Twenty-seven patients had tumors which were clearly aneuploid, 12 (45%) of whom later died. Our study demonstrates the prognostic value of ploidy analysis. The preliminary results indicate that mortality of patients with proliferating tumors is approximately 50% after 2 years. This prognostic is independent of other more classical criteria of tumor staging, namely Dukes' classification, histological differentiation and size of tumor. In the near future, ploidy analysis should be introduced as a standard part of tumor assessment. It clearly provides a valuable prognostic allowing the selection of patients requiring a careful follow-up.