From the University of Torino, Department of Clinical & Biological Sciences, S. Luigi Hospital, Orbassano (Torino), Italy
Authors disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Giorgio Vittorio Scagliotti, MD, University of Torino - Department of Clinical & Biological Sciences, Thoracic Oncology Unit, S. Luigi Hospital, Regione Gonzole 10, 10043 Orbassano (Torino), Italy; e-mail: giorgio.scagliotti{at}unito.it
Overview: Until recently, histologic subtyping of non-small cell lung cancer was not considered a relevant parameter for treatment decisions because of substantial lack of prognostic or predictive information. Consistent data across several phase II and III clinical trials indicate a superior activity of pemetrexed in non-squamous histology. Nowadays, routinely performed diagnostic procedures are increasingly less invasive with minimal amounts of neoplastic tissue or cells to make a pathological diagnosis, and this may hamper further subtype characterization. However, mucin staining and immunohistochemistry can assist the pathologist in finely tuning the diagnosis. Thymidylate synthase, the main molecular target of pemetrexed, has higher baseline mRNA and protein expression in squamous and small cell lung cancer compared with adenocarcinoma. This differential expression may represent a molecularly-based explanation of the superior efficacy of pemetrexed in selected histotypes of non-small cell lung cancer. These molecular findings are hypotheses-generating, which are currently validated in prospective studies.