Abstract
BackgroundPulmonary pleomorphic carcinoma (PPC) is a rare type of non-small-cell lung cancer that belongs to the family of sarcomatoid carcinomas and is associated with poor prognosis. We investigated the expressions of tumor-related genes in resected PPC specimens.MethodsSpecimens resected from patients with PPC from July 2006 through April 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg’s tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of lung cancer, data from stage-matched adenocarcinoma (AC) and squamous cell carcinoma (SCC) cases in our database were also examined.ResultsThe gene expression levels of thymidylate synthase were significantly higher in PPC and SCC as compared to the AC specimens (p < 0.001). The levels of dihydropyrimidine dehydrogenase and thymidine phosphorylase mRNA in PPC showed a similar tendency to those in SCC, in contrast to AC. Furthermore, the expression level of excision repair cross-complementation group 1 mRNA in PPC specimens was similar to that reported in NSCLC, while the level of vascular endothelial growth factor (VEGF) expression was higher as compared to that reported for colorectal cancer.ConclusionsAlthough gene expression of tumor cannot be directly correlated to its sensitivity for anti-cancer drugs, it is likely that PPC tumors are not sensitive to anti-metabolic drugs. Anti-VEGF therapy may be a candidate for PPC, while cisplatin also remains a viable option.
Highlights
A pulmonary pleomorphic carcinoma (PPC) is a rare type of non-small-cell lung cancer (NSCLC) that belongs to the family of sarcomatoid carcinomas [1] and is associated with poor prognosis [2,3,4]
The relative gene expression value for dihydropyrimidine dehydrogenase (DPD) was 2.49 ± 1.70, 2.20 ± 1.18, and 1.59 ± 1.34, respectively (Fig. 2), which was greater in PPC and AC than in squamous cell carcinoma (SCC), with borderline significance (p = 0.0649)
The present findings showed that gene expression levels of thymidylate synthase (TS) mRNA in PPC were significantly higher than in AC, whereas those of DPD and thymidine phosphorylase (TP) mRNA in PPC were similar to those in SCC, in contrast to AC
Summary
Resected specimens from patients with PPC who underwent lung resection from July 2006 through April 2012 at our institutions were investigated. Those from patients who received preoperative induction therapy including chemotherapy or chemoradiotherapy were excluded. Determination of tumor-related gene expression Excised specimens were thinly sliced, tumor segments were collected by micro-dissection to extract mRNA. RTPCR was performed according to Danenberg’s tumor profile (DTP) method [9] for semi-quantitation of mRNA of tumor-related genes (Response Genetics Inc., New York, USA), including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), excision repair cross-complementation group 1 (ERCC1), vascular endothelial growth factor (VEGF), and topoisomerase-1 (TOPO1). Differences were considered significant at P < 0.05, with borderline significance considered at P < 0.10
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