DNA Aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma

Abstract

Inactivation of the p53 gene plays a key role in tumour biology, probably through a disturbed cell cycle control and an increased genetic instability in p53-inactivated tumours. To learn more about the relationship between p53 alterations, proliferation and genetic instability (DNA aneuploidy) in lung cancer patients, specimens of 220 surgically resected lung carcinomas with clinical follow-up information were examined by immunohistochemistry (p53; CM1) and flow cytometry. Nuclear p53 positivity--found in 49.5% of the tumours--was associated with both high S-phase fraction (SPF) and DNA ploidy aberrations. SPF was higher in p53-positive tumours (15.9 +/- 10.2) than in p53-negative tumours (10.3 +/- 8.7; P = 0.03). The rate of p53 positivity was higher in 101 DNA-aneuploid and DNA-multiploid tumours (55%) than in 27 diploid and peridiploid carcinomas (33%; P = 0.0512). These results are consistent with an in vivo role of p53 inactivation for increased proliferative activity and development of genomic instability in lung cancer. There was no association between SPF and prognosis. Although prognosis was worse in DNA-aneuploid and multiploid tumours than in diploid, peridiploid and tetraploid carcinomas (P = 0.029), DNA ploidy was not an independent predictor of poor prognosis in multivariate analysis. These data show that DNA-flow cytometry has little prognostic value for patients with resected non-small-cell lung carcinoma.

Expression ofp16INK4A and alterations of the 9p21-23 chromosome region in non-small-cell lung carcinomas: Relationship with tumor growth parameters and ploidy status

“…Moreover, the correlation observed with smoking possibly indicates a tumor response to tobacco derivatives (Barsky et al, 1998). Finally, the unfavorable effect of aneuploidy on patients' outcome has been noted (Zimmerman et al, 1987), and probably illustrates the cooperative impact of de-regulated tumor kinetics, as observed in the current study and other studies (Dalquen et al, 1997, and references therein), and impaired immune surveillance remarked by certain researchers (Redondo et al, 1997, and references therein).…”

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

“…A total of 35 studies fulfilled the criteria of selection (Zimmerman et al, 1987;Tirindelli-Danesi et al, 1987;Ten Velde et al, 1988;Volm et al, 1988;Yamaoka et al, 1989;Cibas et al, 1989;Dazzi et al, 1990;Isobe et al, 1990;Sahin et al, 1990;Shiota et al, 1990;Miyamato et al, 1991;Mizumoto et al, 1991;Liewald et al, 1992;Ogawa et al, 1992;Filderman et al, 1992;Morkve et al, 1993;Cheon et al, 1993;Pence et al, 1993;Rice et al, 1993;Ichinose et al, 1993;Lima et al, 1993;Shimizu et al, 1993;Yu et al, 1993;Usuda et al, 1994;Salvati et al, 1994;Tanaka et al, 1995;Pujol et al, 1996;Huang et al, 1996;Nagai et al, 1996;Jeanfaivre et al, 1997;Muguerza et al, 1997;Kolodzeijski et al, 1997;Graziano et al, 1997;Dalquen et al, 1997;Asamura et al, 1999; (Table 1)). Among the 4033 assessable patients, 2626 suffered from NSCLC with aneuploid DNA content (overall frequency of aneuploidy: 0.65; 95% Cl: (0.64-0.67)).…”

“…British Journal of Cancer (2001) Zimmerman;1987 Tirindelli;1987 Ten velde;1988 Volm;1988 Yamaoka;1989 Cibas;1989 Dazzi;1990 Isobe;1990 Sahin;1990 Shiota;1990 Miyamoto;1991 Mizumoto;1991 Liewald;1992 Ogawa;1992 Filderman;1992 Morkve;1993 Cheon;1993 Pence;1993 Rice;1993 Ichinose;1993 Yu;1993 Lima;1993 Shimizu;1993 Usuda;1994 Salvati;1994 Tanaka;1995 Pujol;1996 Huang;1996 Nagai;1996 Jeanfaivre;1997 Muguerza;1997 Kolodziejski;1997 Graziano;1997 Dalquen;1997 Asamura;1999 Overall iploidy better Aneuploidy better 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 I yr D…”

Stratification of the biologic aggressiveness of non-small cell lung cancer using DNA flow cytometry and immunohistochemistry for the retinoblastoma protein

“…We, therefore, examined proliferative activity and treatment results in NSCLC. Some reports of lung cancer have found that DNA aneuploid tumors had higher proliferative activity than DNA diploid tumors [24,25,27,39]. This has not been consistently seen, perhaps because of the discrepancy in measurements.…”

“…Past reports have not always recognized SPF as a prognostic factor after surgery in NSCLC [23][24][25][26][27][28]. This disagreement may be due in part to differences in patient background and in sample processing among institutions [18,29].…”