The prognostic role of the DNA ploidy pattern in colorectal cancer analysis using paraffin-embedded tissue by an improved method

Abstract

To assess the prognostic value of DNA ploidy in colorectal cancer, compared with the histopathological findings, paraffin-embedded surgical specimens from 330 patients who underwent resection for primary adenocarcinoma were studied using a new modified method of flow cytometry. Of these specimens, 141 were DNA diploid and 189, DNA aneuploid, among which there were 3 DNA hypodiploid lesions. Of the ten variables studied in curative resection, DNA ploidy ranked fourth in prognostic significance according to the linear trend by the chi 2 test, after nodal status, grade of cellular differentiation, and degree of invasive growth, if the DNA ploidy pattern was classified into three categories. Conversely, DNA ploidy was the sixth most significant factor if DNA hypodiploidy was included in the DNA aneuploidy. The Cox multivariate analysis showed that DNA ploidy was one of the five significant factors independently determining prognosis; however, if adjustment for the modified Dukes' stage was made by the Mantel-Haenszel test, the survival difference between the diploid and aneuploid groups did not reach a statistically significant level. Thus, we conclude that from a practical point of view, DNA ploidy is not an essential factor which must be combined with histopathological variables for a better prediction of patient outcome.

KRAS and aneusomy of chromosomes 4, 10 and 12 in colorectal carcinomas

“…Furthermore, quantification of FISH signals has become a routine in predictive molecular pathology like HER2 analysis. In general, the frequency of aneuploid and near triploid cases of our FISH study is comparable with published DNA cytometry data [8,21,27]. In particular, our recent DNA ploidy analysis confirmed the presence of hypodiploid colon tumors and pointed to a putative relevance of hypodiploidy in the transition from adenomas to carcinomas [21].…”

“…The ploidy status of tumors is usually determined by DNA measurement using either flow cytometry or static DNA image analysis [8,21,27]. FISH represents an interesting alternative method because it is widely used in the diagnostic setup of many pathological institutes.…”

Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis

“…Generally, a more detailed assessment—for example, using array comparative genomic hybridisation (arrayCGH)—is impractical for large series. Nonetheless, many studies have reported that CIN+ measured by flow cytometry confers a worse prognosis; however, this observation is neither universal5 6 nor always significant 7 – 9. Consequently, it has been argued consistently that measuring CIN does not add further prognostic information to standard pathological and histological staging 10 – 13.…”

Stage-specific frequency and prognostic significance of aneuploidy in patients with sporadic colorectal cancer—a meta-analysis and current overview

“…There were 12 studies which performed a multivariate analysis for OS. Out of these, six described statistical significance for aneuploidy [14,15,63,71,38,41]. For RFS, five studies performed multivariate analysis and two revealed statistical significance for the ploidy status [14,40].…”

“…Twenty-two studies tested for differences and/or correlations between aneuploidy rates and tumor stages. Out of these, eight studies (36.4 %) described statistical significance [17,18,42,54,56,58,43,41]. This particular aspect was focused on in our meta-analysis.…”