Cellular proliferation markers in the evaluation of human cancer

Our knowledge of normal growth regulatory mechanisms, and of the disordered growth that occurs during tumorigenesis, has greatly increased during the past decade. In particular, these studies have emphasized the importance of chromosomal alterations, genetic heterogeneity, and cell proliferation in tumorigenesis and metastasis. As a result, the early diagnosis and treatment of malignancy appear to be even more important than previously recognized. Clinical studies of tumor proliferative activity were first conducted by thymidine-labeling techniques and more recently by flow cytometric analysis of DNA content. This information appears to provide important information that directly relates to tumor behavior and is of great prognostic significance in many tumors. In contrast, total nuclear DNA content, as measured by flow cytometry or image analysis, appears to be an "epi-phenomenon," and its clinical significance varies in different tumors. The potential clinical value of this research is enormous, because a rapid, accurate nonradioisotopic flow cytometric determination of tumor kinetic parameters, simultaneously with DNA content and surface antigen expression, would provide information of great importance for determining patient prognosis and making therapeutic decisions. Under these circumstances, analysis of DNA content and proliferative activity should be applied cautiously to patient care. Stringent quality control should be exercised, and the potential significance and limitations of these data should be clearly provided to the requesting physician. Most importantly, additional research during the next few years will provide answers to the many questions that remain about the appropriate clinical role of this information. As Stanbridge and Nowell stated at the conclusion of a recent Cold Spring Harbor meeting on the Origins of Human Cancer, "We have come a long way. . . and we have a very long way to go."