title: Differential Thymidylate Synthase Expression in Different Variants of Large-Cell Carcinoma of the Lung.
abstract: PURPOSE: In non-small cell lung cancer, higher thymidylate synthase (TS) levels have been reported in squamous cell carcinoma (SCC) compared with adenocarcinoma (ADC). Data on TS expression in large-cell carcinoma (LCC) are scanty. EXPERIMENTAL DESIGN: TS mRNA and protein levels were analyzed in 42 surgical cases of pulmonary LCC, including 8 large-cell neuroendocrine carcinomas, and were compared with controls represented by ADC (n = 41), SCC (n = 30), and small-cell lung carcinoma (SCLC; n = 33). TS levels were also correlated with the expression of Ki67 and E2F1. Moreover, the reliability of TS expression analysis was assessed in 22 matched cytologic and surgical specimens of non-small cell lung cancer. RESULTS: TS mRNA levels of LCC were comparable with those of control SCC, but significantly higher than those of ADC (P < 0.001) and lower than SCLC (P < 0.001). A correlation between TS mRNA and protein levels was observed in control ADC and SCC, but not in LCC. Large-cell neuroendocrine carcinomas had the highest TS expression, whereas in non-neuroendocrine LCCs, TS protein levels were significantly higher (P = 0.02) in LCC immunoreactive for p63 and desmocollin3 (markers of squamous differentiation) than those expressing TTF-1 (a marker of ADC). Both E2F1 and Ki67 levels were not correlated with TS in LCCs. Finally, a linear correlation in TS protein levels was observed between matched cytologic and surgical specimens. CONCLUSION: The pulmonary LCC immunoprofile may resemble that of SCCs or ADCs. This immunoprofile is associated with differential TS expression levels, which may support a more appropriate therapeutic strategy decision. (Clin Cancer Res 2009;15(24):7547-52).
authors.affiliation: Authors' Affiliation: Department of Clinical and Biological Sciences, University of Torino at San Luigi Hospital, Orbassano (Turin), Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Monica
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Paolo
authors.initials: P
authors.lastname: Ceppi
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.forename: Alberto
authors.initials: A
authors.lastname: Cambieri
authors.forename: Marco
authors.initials: M
authors.lastname: Lo Iacono
authors.forename: Silvia
authors.initials: S
authors.lastname: Saviozzi
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti