DNA ploidy and protein content in bronchioloalveolar carcinoma multi-variable flow cytometry

Multi-variable flow cytometry studies were done on paraffin-embedded surgical specimens from 97 patients with bronchiolalveolar carcinoma (BAC) and on 10 normal lung tissue specimens to assess the value of nuclear protein content besides DNA ploidy. Tumor tissues were stained for DNA content with propidium iodide and for protein content with fluorescein isothiocyanate. DNA ploidy measurements were successful in 87 of the 97 specimens. Twenty-four (28%) specimens were DNA diploid, and 63 (72%) were DNA nondiploid (DNA tetraploid or DNA aneuploid). There was no significant difference in survival between patients with DNA diploid and with DNA nondiploid tumors (P = 0.69). The protein histogram pattern was bimodal in 26/87 (30%) of patients; these had significantly shorter survival than patients with either normal or right-shift protein histogram patterns (61/87) (P = 0.0033). The nuclear protein measurement was an independent prognostic indicator when corrected for tumor grade and tumor size in a Cox model analysis (P = 0.04). The nuclear protein measurement correlated with nuclear size as determined by nuclear volume measurements. The combination of DNA ploidy, protein, and cell size measurements by flow cytometry provide a useful biologic basis for the variable prognosis seen with BAC tumors.