No abstract

It is estimated that in 1993 there will be > 155,000 new cases of adenocarcinoma of the colon and rectum in the United States (1). Surgical resectability offers the best chance of cure, and the results of surgical and pathologic staging are important factors in deciding whether the patient should be offered adjuvant chemotherapy in the case of colon cancer or combined chemotherapy and radiation therapy for patients with rectal cancer. Because there is significant variation in the rate of recurrence and overall survival within TNM stage categories, there is a need for additional, independent factors to better predict outcome in patients that have had a potentially curative surgical resection.To assess the available data on the possible clinical utility of DNA flow cytometry, a Consensus Conference was recently held. The aims of this work, which reports the conclusions from the ColodRectum Organ System Group that participated in the conference, are: (1) to analyze the current published literature regarding the clinical utility of flow cytometric measurements of DNA ploidy and cell proliferative activity (PA, based on %S or %S + G2M) as prognostic factors for recurrence and survival, and (2) to suggest guidelines and standards for future investigation of DNA ploidy and PA so that these measurements can be appropriately applied to specific colorectal cancer patient care situations.The majority of studies in the literature (2-23; Table 1) suggest that DNA ploidy has significant prognostic value. There are no reports demonstrating DNA aneuploidy as a favorable feature, but several reports (e.g., 3,7,14,18,19,20,21,24) have concluded that DNA ploidy provides no additional significant prognostic information, particularly when considered following multivariate analysis that includes traditional prognostic factors. With exceptions (e.g., 7,17,25), most studies suggest a trend toward an increasing frequency of DNA aneuploidy in higher Dukes stages and for tumors located in the left colon and rectum. Although there are exceptions, most of the published studies suggest that DNA ploidy and PA are unrelated to numerous clinical and pathologic observations in colorectal cancers (26). These include evaluation of age, tumor grade, infiltrative growth pattern, host inflammatory and desmoplastic response, presence of vascular invasion, carcinoembryonic antigen, or mutant p53 status. Fewer studies have examined the prognostic significance of PA. As summarized in Table 2, these series with one exception (7) have found PA to be a significant prognostic factor in colorectal cancer. These conclusions were reached despite the use of four different mathematical methods for S-phase modeling, some with debris subtraction and some without. This emphasizes the need for careful methodological description and, wherever possible, standardization of methods as described subsequently.Contradictory study results have been obtained following the use of a wide variety of technical and analytical methods, many of which may compromise the accurate det...

The HyperLog transform is easily implemented in computer systems and results in display systems that present compensated data in an unbiased manner.

Developing a reliable and quantitative assessment of the potential virulence of a malignancy has been a long-standing goal in clinical cytometry. DNA histogram analysis provides valuable information on the cycling activity of a tumor population through S-phase estimates; it also identifies nondiploid populations, a possible indicator of genetic instability and subsequent predisposition to metastasis. Because of conflicting studies in the literature, the clinical relevance of both of these potential prognostic markers has been questioned for the management of breast cancer patients. The purposes of this study are to present a set of 10 adjustments derived from a single large study that optimizes the prognostic strength of both DNA ploidy and S-phase and to test the validity of this approach on two other large multicenter studies. Ten adjustments to both DNA ploidy and S-phase were developed from a single node-negative breast cancer database from Baylor College (n ‫؍‬ 961 cases). Seven of the adjustments were used to reclassify histograms into low-risk and high-risk ploidy patterns based on aneuploid fraction and DNA index optimum thresholds resulting in prognostic P values changing from little (P < 0.02) or no significance to P < 0.000005. Other databases from Sweden (n ‫؍‬ 210 cases) and France (n ‫؍‬ 220 cases) demonstrated similar improvement of DNA ploidy prognostic significance, P < 0.02 to P < 0.0009 and P < 0.12 to P < 0.002, respectively. Three other adjustments were applied to diploid and aneuploid S-phases. These adjustments eliminated a spurious correlation between DNA ploidy and S-phase and enabled them to combine independently into a powerful prognostic model capable of stratifying patients into low, intermediate, and high-risk groups (P < 0.000005). When the Baylor prognostic model was applied to the Sweden and French databases, similar significant patient stratifications were observed (P < 0.0003 and P < 0.00001, respectively). The successful transference of the Baylor prognostic model to other studies suggests that the proposed adjustments may play an important role in standardizing this test and provide valuable prognostic information to those involved in the management of breast cancer patients. Cytometry (Comm. Clin. Cytometry) 46: 121-135, 2001.