Thymidylate synthase expression in adenosquamous carcinoma of lung.

Abstract

10563 Background: Thymidylate synthase (TS) expression is higher in squamous (SQ) cell carcinoma than in adenocarcinoma (AD) of lung. Higher TS level has been related to the poor efficacy of pemetrexed in SQ carcinoma. There is limited data on TS expression in adenosquamous (AS) carcinoma, a distinct subtype of lung cancer, containing both squamous and glandular differentiation. Methods: TS protein levels were evaluated by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded (FFPE) specimens from 163 patients, including 17 SQ, 19 AS, and 121 AD tumors by two independent investigators. Based on the cross-product of the intensity score and percentage of positive cells an H-score (range of 0-200) was generated. For the AS samples, the squamous and glandular components were also separately assessed. In order to assess whether TS expression was correlated more intra- versus inter-specimen, permutation method was used to calculate the correlation coefficients. The results were compared based on the random permutation with the actual coefficient between two components within the same specimen (rho=0.4832505) (Permutation p-value < 0.5). One way ANOVA was conducted to compare the mean values of the three groups: SQ, AS, and AD. Results: The average H-score of TS expression in AS, SQ and AD samples were 64.7%, 66.5% and 32.5% respectively (p=0.0001). Consistent with previous reports, TS expression was significantly higher in SQ than AD carcinoma. Interestingly, TS expression in AS carcinoma was near-identical to SQ carcinoma, rather than falling between AD and SQ carcinoma. In AS samples the expression of TS was more closely correlated within the two components than would be expected by random chance alone, suggestive of a tumor-specific rather than a histology-dependent determinant of TS expression. Conclusions: The current study identifies high TS expression in AS carcinoma of lung similar to SQ tumors and the expression of TS appears to be driven more by individual tumor determinants than histological pattern. Given that TS is the main target of pemetrexed and the similarity of TS expression between SQ carcinoma and AS carcinoma, it is possible that pemetrexed may also have inferior clinical activity in AS carcinoma of lung.