Accurate Classification of Non–Small Cell Lung Carcinoma Using a Novel MicroRNA-Based Approach

Abstract

Purpose: Advances in targeted lung cancer therapy now demand accurate classification of non-small cell lung cancer (NSCLC). MicroRNAs (miRNA) are recently discovered short, noncoding genes that play essential roles in tissue differentiation during normal development and tumorigenesis. For example, hsamiR-205 is a miRNA that is highly expressed in lung squamous cell carcinomas (SqCC) but not in lung adenocarcinomas. The differential expression of miRNAs could be exploited to distinguish these tumor types.Experimental Design: One hundred and two resected NSCLCs were classified as SqCC or adenocarcinoma based on their histologic features and immunohistochemical profiles. Corresponding preoperative biopsies/aspirates that had been originally diagnosed as poorly differentiated NSCLCs were available for 21 cases. A quantitative reverse transcription-PCR diagnostic assay that measures the expression level of hsa-miR-205 was used to classify the carcinomas as SqCC or adenocarcinoma based solely on expression levels. The two sets of diagnoses were compared.Results: Using standard pathologic methods of classification (i.e., microscopy and immunohistochemistry), 52 resected lung carcinomas were classified as SqCCs and 50 as adenocarcinomas. There was 100% concordance between the diagnoses established by conventional and miRNA-based methods. MiRNA profiling also correctly classified 20 of the 21 preoperative biopsy specimens.Conclusions: MiRNA profiling is a highly reliable strategy for classifying NSCLCs. Indeed, classification is consistently accurate even in small biopsies/aspirates of poorly differentiated tumors. Confirmation of its reliability across the full range of tumor grades and specimen types represents an important step toward broad application. Clin Cancer Res; 16(2); 610-9. ©2010 AACR.Lung cancer is the leading cause of cancer-related death in both men and women worldwide. In the United States, there are over 215,000 new cases of lung cancer each year resulting in over 160,000 deaths annually (1). Eighty-five percent of these lung cancers are non-small cell lung cancers (NSCLC), a heterogeneous group comprised of mostly squamous cell carcinomas (SqCC) and adenocarcinomas. In the past, the only diagnostic branch point in the classification of lung cancers that carried any relevance was the distinction between small cell carcinoma and NSCLC. Further subclassification of the NSCLCs has not been important from a therapeutic or prognostic standpoint. The recent emergence of targeted lung cancer therapies directed against specific cellular alterations, however, now demands the most precise classification possible for NSCLCs. For example, lung adenocarcinomas are more likely to harbor activating mutations of epidermal growth factor receptor and, in turn, are more likely to respond to epidermal growth factor receptor tyrosine kinase inhibitors (2). Similarly, certain angiogenesis inhibitors such as bevacizumab are more effective in the treatment of adenocarcinomas. Not only is bevacizumab less effective in t...

Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma

“…The clinical therapy of ADC and SCC is usually based on histopathological features (Bishop et al, 2010). However, there is an urgent need to explore special treatment of these two sub-types.…”

Genetic and epigenetic changes in lung carcinoma and their clinical implications

“…Has-miR-205, which suppresses epithelial-to-mesenchymal transition, has been identified as a highly specific marker for squamous carcinoma of the lung. 147,148 A wellstudied miRNA in lung cancer is miR-21. In a group of 48 lung adenocarcinomas/squamous cell carcinomas, overexpression of mature miR-21 was found in 52% of cases compared with their corresponding non-cancerous tissues.…”

MicroRNA-29b is involved in the Src-ID1 signaling pathway and is dysregulated in human lung adenocarcinoma

“…In human cancers, including lung cancer, dysregulated miRNAs can act as oncogenes or tumor suppressors (Croce, 2009). Several groups showed that miRNA profiling allows to distinguish histological lung cancer subtypes (Lebanony et al, 2009;Bishop et al, 2010). Furthermore, specific miRNA profiles have been evaluated to predict prognosis and disease recurrence in early-stage lung cancer (Yu et al, 2008;Patnaik et al, 2010).…”