Flow Cytometric Measurement of Aneuploid DNA Content Correlates with High S-Phase Fraction and Poor Prognosis in Patients with Non-Small-Cell Lung Cancer

Abstract

Cellular DNA content (ploidy) and proliferation activity (e.g., S-phase fraction) measured by flow cytometry have been usually related to the biologic aggressiveness of various neoplasms. In this study, these parameters were analyzed in paraffin-embedded tumor specimens from 43 cases of resected non-small-cell lung cancer (NSCLC). Additionally, the correlation of them with both prognosis and a variety of clinic-pathological features were investigated. The stage and the appearance of both local recurrence and metastasis were related to overall survival of patients. Twenty-two tumors (51.2%) had a diploid DNA distribution, while 21 were aneuploid (48.8%). The mean of aneuploidy was 1.6% ± 0.3%. A correlation was found between ploidy and survival as well as with the appearance of local recurrence and/or metastasis. The mean values of S-phase fraction of diploid and aneuploid tumors were 16.7 ± 11.3% and 32.9 ± 12.1%, respectively, which were significantly different (P=0.0022). Similar results were obtained analyzing the proliferation index (sum of cells in S and G2/M phases of cell cycle) (P=0.0040). However, no correlation between these parameters and both overall survival of patients and clinicopathological features was observed. Our results could suggest the potential use of ploidy analysis as a useful complement of TNM stage in NSCLC.

Novel APC gene mutations associated with protein alteration in diffuse type gastric cancer

“…Four distinct phases could be recognized in a proliferating cell population: the G1, S- (DNA synthesis phase), G2- and M-phase (mitosis). G2- and M-phase could not be discriminated because of the presence of identical DNA content [ 28 ]. The data obtained was analyzed using the ModFit LT software (DNA Modeling System) version 2.0 (Verity Software House, Inc.) and single parameter histograms were obtained.…”

Prognostic Significance of N-Glycolyl GM3 Ganglioside Expression in Non-Small Cell Lung Carcinoma Patients: New Evidences

“…The flow cytometry methodology using nuclei isolated from formalin-fixed and paraffin-embedded tissues was used as it was previously described in [ 5 ]. The percentage of cells in S and G 2 /M phases of cell cycle was calculated for each sample based on DNA histograms.…”

“…There are two main forms of the disease but non-small cell lung cancer (NSCLC) represents about 80–85% of these tumors [ 1 , 2 ]. Consequently, numerous studies are currently focusing on the selection of newer biological and molecular prognostic factors as a potential complement of TNM (tumor, node, metastasis) staging system [ 3 – 5 ]. In line with this, unusual glycosylated gangliosides have been identified by immunohistochemistry (IHC) in NSCLC, also becoming attractive targets for immunotherapy [ 6 , 7 ].…”

Proliferation and stemness preservation of human adipose-derived stem cells by surface-modified in situ TiO2 nanofibrous surfaces

“…As revealed from the DNA histogram in Figure 5, no evidence that aneuploidy was found on either surface since there is only a single peak in the G0/G1 phase. 33 In the cell cycle, the primary phases that are responsible for cell proliferation are the S and G2/M phases, 34 and therefore the proliferation index (sum of the percentage of cells in S and G2/M phases) was calculated to assess the cell proliferation capacity of both surfaces (Table 2). In the G0/G1 phase, TiO 2 nanofibrous surfaces showed a significantly lower percentage of cells compared to the control surfaces.…”