Interrelationships of DNA-ploidy and cell proliferation markers with T-stage and N-stage in primary laryngeal tumors.

Abstract

The purpose of this study was to evaluate the interrelationships of DNA-ploidy and cell proliferation markers with T-stage and N-stage in primary laryngeal tumors. DNA-index, S-phase fraction (SPF), 5-bromo-2'-deoxy-uridine (BrdUrd)-labeling index (LI), duration of S-phase (Ts), and potential doubling time (Tpot) were determined by flow cytometry. T-stage and N-stage were assessed in accordance with the TNM classification system (UICC 1987). T1-2-, when compared with T3-4-stage tumors, had significantly higher LI values (independent from N-stage) resulting in lower Tpot values. No such relationship was found with respect to N-stage. N1-3 tumors, as opposed to NO tumors, appeared to be characterized by a significantly shorter Ts (and, hence, a shorter Tpot). Ts values appeared to vary considerably (range 1.9-6.2 h). For DNA-aneuploidy, as opposed to DNA-diploidy, a significantly higher geometric mean LI was noted. Locally advanced (T3-4) tumors, when compared with T1-2 tumors, were characterized by a significantly higher percentage of DNA-aneuploidy. The reported lack of prognostic relevance of cell proliferation markers to predict radiation treatment efficacy may relate to a decreased proliferative capacity (LI, Tpot) in locally advanced (T3-4) tumors, as found in our series. In laryngeal tumors, the predictive value of cell proliferation markers (LI, Tpot) should, therefore, be evaluated after stratification for T-stage. The existence of higher LI values in DNA-aneuploidy tumors was confirmed in our series, stressing the need for distinction of DNA-diploid tumor cells from DNA-diploid normal cells. The prognostic potential of DNA-index was confirmed.