DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy

Abstract

We aimed to investigate whether biological factors related to radiosensitivity and chemosensitivity have prognostic significance in non-small-cell-lung-cancer (NSCLC) patients treated with daily low doses of cisplatin and radiotherapy. We treated 27 NSCLC patients with concomitant daily lowdose cisplatin and radiotherapy between 1993 and 1995. Tumour specimens were analyzed for p53 and bcl-2 expression, and for cell proliferation using antibodies against ki-67. In addition, apoptosis was measured by an end-labeling technique (TUNEL). Finally, cisplatin-induced DNA modification in buccal cells was assessed immunocytochemically using a specific anti-serum. Univariate and multivariate analyses were performed to assess the association between the different variables and survival. The median follow-up was 41 months, and 21 patients (78%) have died. In a univariate analysis, age, tumour stage and cisplatin-DNA-adduct staining were the only factors significantly associated with survival (p < 0.05, log-rank test). p53, bcl-2, Ki-67 and apoptosis showed no relationship with outcome. Multivariate analysis revealed that cisplatin-DNA-adduct staining remained an independent prognostic factor (hazard ratio, 0.10, 95% CI, 0.02-0.49), with shorter survival times for patients with low adduct staining.

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

“…Immunohistochemistry used to reveal Ki-67 protein was not always performed with the same antibody: clone Mib-1 in the majority of the studies (Costes et al, 1995;Bohm et al, 1996;Fontanini et al, 1996;Bellotti et al, 1997;Ishida et al, 1997;Komaki et al, 1998;Dazzi et al, 1999;Dingemans et al, 1999Dingemans et al, , 2001Santinelli et al, 1999;Cagini et al, 2000;Demarchi et al, 2000;Hommura et al, 2000;Nguyen et al, 2000;Shiba et al, 2000Shiba et al, , 2001van de Vaart et al, 2000;Ferreira et al, 2001;Hayashi et al, 2001;Puglisi et al, 2001Puglisi et al, , 2002Ramnath et al, 2001;Tsoli et al, 2001;Minami et al, 2002;Rigau et al, 2002), antibodies coming from a firm selling several clones but without mention of the clone used (Hayashi et al, 1993;Pence et al, 1993;Kawai et al, 1994;Giaccone et al, 1995;Pujol et al, 1996;Mehdi et al, 1998;Soomro et al, 1998;Carbognani et al, 2002); any mention of the antibodies used (Tungekar et al, 1991;Harpole Jr et al, 1995Giatromanolaki et al, 1996a, b;D'Amico et al, 1999D'Amico et al, , 2000Carvalho et al, 2000;Pelosi et al, 2001)…”

“…In total, 42 studies published between 1991 and 2002 were selected for this systematic review (Tungekar et al, 1991;Hayashi et al, 1993;Pence et al, 1993;Kawai et al, 1994;Costes et al, 1995;Giaccone et al, 1995;Harpole, Jr et al, 1995Bohm et al, 1996;Fontanini et al, 1996;Giatromanolaki et al, 1996a, b;Pujol et al, 1996;Bellotti et al, 1997;Ishida et al, 1997;Komaki et al, 1998;Mehdi et al, 1998;Soomro et al, 1998;D'Amico et al, 1999D'Amico et al, , 2000Dazzi et al, 1999;Dingemans et al, 1999Dingemans et al, , 2001Santinelli et al, 1999;Cagini et al, 2000;Carvalho et al, 2000;Demarchi et al, 2000;Hommura et al, 2000;Nguyen et al, 2000;Shiba et al, 2000Shiba et al, , 2001van de Vaart et al, 2000;Ferreira et al, 2001;Hayashi et al, 2001;Pelosi et al, 2001;Puglisi et al, 2001Puglisi et al, , 2002Ramnath et al, 2001;Tsoli et al, 2001;Carbognani et al, 2002;Minami et al, 2002;Rigau et al, 2002). Five were excluded because an identical patients cohort was used in another selected publication (references excluded/includ...…”

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

“…Cytotoxicity from cisplatin and other platinum-containing drugs, such as oxaliplatin, results from the formation of platinum DNA adducts (Schellens et al, 1996;van de Vaart et al, 2000). One determinant of the level of platinum DNA adducts in the tissue of patients treated with platinum-containing drugs is the rate of DNA repair.…”

The Demonstration of Immunohistochemical Biomarkers in Methyl Methacrylate-Embedded Plucked Human Hair Follicles

“…Normal tissuebased oncology biomarker studies have been performed with success using peripheral blood mononuclear cells (Cohen et al, 2003;Peralba et al, 2003), exfoliated buccal squamous cells (van de Vaart et al, 2000;Adjei et al, 2003), punch biopsies of the skin (Albanell et al, 2002;Malik et al, 2003;Vanhoefer et al, 2004) and punch biopsies of buccal mucosa (Camidge et al, 2005a).…”