The Role of Molecular Pathology in Non-Small-Cell Lung Carcinoma—Now and in the Future

Abstract

In recent years, better understanding of the molecular biology of non-small-cell lung carcinoma (nsclc) has led to a revolution in the work-up of these neoplasms. As a pathology diagnosis, "nsclc" without further attempt at subclassification is no longer accepted as a standard of care; separating squamous cell carcinoma from adenocarcinoma and large-cell carcinoma carries implications for prognosis and treatment decisions. Currently, detection of the presence in nsclc of mutations involving the epidermal growth factor receptor (EGFR) gene and fusion of the N-terminal portion of the protein encoded by EML4 (echinoderm microtubule-associated protein-like 4 gene) with the intracellular signaling portion of the receptor tyrosine kinase encoded by ALK (anaplastic lymphoma kinase gene)-that is, EML4-ALK-and variants has become routine in many centres because patients having tumours harbouring such alterations might benefit from tyrosine kinase inhibitors as part of their treatment regimen.The purpose of the present review is to highlight important aspects of the screening for molecular derangements in nsclc and to briefly discuss the emergence of possible future biomarkers.

Detection of Common and Less Frequent <b><i>EGFR</i></b> Mutations in Cytological Samples of Lung Cancer

“…Outstanding results have been obtained with the use of anti-EGFR TKIs mainly for non-small cell carcinoma other than squamous carcinoma. Many studies underlined the relevance of EGFR mutation analysis in the stratification of patients for a more ‘personalized' treatment [1,2,3,7,8]. Cancer cells with EGFR mutations do not onlypossess a growth advantage over cells with wild-type EGFR but also show increased sensitivity to the anti-EGFR TKIs with a better progression-free survival rate [13].…”

“…The recent developments in molecular genetics highlight the importance of patient selection for TKIs also in the field of lung oncology [3,7,8,9,10]. Since 2004, the application of molecular genetic assays to neoplastic tissue, including cytological samples, has been considered a new standard of care in the field of lung cancer [9].…”

“…The evidence of functional activation of EGFR (epidermal growth factor receptor) as well as ALK (anaplastic lymphoma kinase) gene rearrangement seems to be of benefit for both prognostic and predictive assessment of therapeutic response to targeted therapy, e.g. tyrosine kinase inhibitors (TKIs) [7,8]. …”

Correlation analysis between an IL-6 genetic polymorphism and non-small cell lung cancer prognosis

“…There are two primary genotypes formed by this SNP: the high IL-6 production type (GG and GC genotypes) and low IL-6 production type (CC genotype). Genetic studies have shown that the frequency of the G allele at position -174 has racial and ethnic differences (Brandao et al, 2012). The first goal of this study was to investigate the role of the -174G/C SNP in the IL-6 gene on NSCLC prognosis.…”

10.5937/mckg48-2741 = New pharmacological strategies in the treatment of non-small cell lung cancer

“…Glavna uloga karcinoma pluća, a posebno NSCLC posledica je više faktora među kojima su: veliki morbiditet, nepostojanje efikasne terapije koja bi produžila period preživljavanja bez progresije bolesti (progression free survival-PFS) nakon primenjenog lečenja, i još uvek mali broj preživelih bolesnika (često bivših pušača) u odmaklom stadijumu karcinoma pluća, čiji se životni vek i dalje meri u mesecima (1).…”