Methodologic sources of errors in image and flow cytometric DNA assessments of the malignancy potential of prostatic...

Considerable controversy exists about the value of using cytometric assessments of nuclear DNA ploidy patterns from neoplastic parenchymal cells of prostatic carcinomas as a supplement to conventional clinicopathologic data in an assessment of malignancy potential in neoplastic disease. To a great extent, the controversy is of methodologic origin. By revealing common pitfalls in this kind of DNA cytometry and by suggesting means to avoid or at least to reduce them, a realistic assessment can ultimately be made of the prognostic values of this technique: (1) the results of DNA assessments using flow cytometry and image cytometry should be combined (advantages and disadvantages with the two techniques outbalance each other); (2) the cytometric DNA ploidy pattern must always be correlated with results of histopathologic assessments and clinical data; (3) a standardization of DNA histograms obtained by means of both flow DNA cytometry and image DNA cytometry must be made with precise definitions of "diploidy," "tetraploidy," and "aneuploidy"; (4) the subjective component in classifying DNA histograms can be reduced by means of a computerized evaluation technique; (5) the degree of intratumoral variation in DNA ploidy patterns of neoplastic cell nuclei must be established by means of assessments of multiple biopsy specimens from widely different parts of a carcinoma; and (6) foci of a previously poor recognized neuroendocrine phenotype of neoplastic parenchymal cells are ubiquitous in prostatic carcinomas, particularly in anaplastic adenocarcinomas. Today, the DNA ploidy pattern of this phenotype can be assessed by means of a new image DNA cytometry technique.