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Published on: January 7, 2019
Classification of non-small cell lung carcinoma in transthoracic needle specimens using microRNA expression profiling
Ambrogio Fassina1, Rocco Cappellesso1, Matteo Fassan1
1Department of Diagnostic Medical Sciences and Special Therapies, Surgical Pathology and Cytopathology Unit, University of Padova, Padova (PD), Italy.
Background:
Emerging targeted lung cancer therapies require the accurate morphologic subclassification of non-small cell lung cancer (NSCLC), even in scant and distorted specimens obtained by transthoracic needle aspiration (TTNA). MicroRNAs (miRNAs) are small noncoding genes recently reported as useful in differentiating squamous cell carcinoma (SCC) from adenocarcinoma (AD) in resected tumor specimens. We investigated their ability to do so in TTNA specimens.
Methods:
Smears, immunocytochemistry slides, and corresponding cell blocks of 31 NSCLC TTNA specimens were retrieved and classified as AD or SCC based on their cytologic features and immunocytochemical profiles. Data on EGFR and K-RAS mutational status were available for all cases of AD. We quantified the hsa-let-7 family and hsa-miR-205 by quantitative reverse transcription-polymerase chain reaction and compared the miRNA expression levels in AD and SCC using Student t test.
Results:
Eighteen cases were classified as AD and 13 as SCC by light microscopy and immunocytochemistry. miRNA expression profiles demonstrated considerable, statistically significant differences between AD and SCC, showing an upregulation of hsa-let-7a, hsa-let-7b, hsa-let-7c,hsa-let-7f, hsa-let-7g, hsa-let-7i, and hsa-miR-98 and a downregulation of hsa-miR-205 in AD specimens (all P < .05; t test).
Conclusions:
Profiling the hsa-let-7 family and hsa-miR-205 is a promising method for differentiating AD from SCC, even in such small specimens as transthoracic aspirates. Subject to the validation of these findings in further, larger studies, this could prove to be a reliable, standardizable tool for the subclassification of NSCLC.
Insights
MicroRNA profiling effectively distinguishes non-small cell lung cancer subtypes, adenocarcinoma and squamous cell carcinoma, even in small transthoracic needle aspiration specimens. This method shows promise for accurate lung cancer subclassification.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Accurate subclassification of non-small cell lung cancer (NSCLC) is crucial for emerging targeted therapies.
- Transthoracic needle aspiration (TTNA) provides scant specimens, posing challenges for morphologic subclassification.
- MicroRNAs (miRNAs) show potential for differentiating NSCLC subtypes in larger tumor samples.
Purpose of the Study:
- To investigate the utility of specific microRNAs (miRNAs) in differentiating between adenocarcinoma (AD) and squamous cell carcinoma (SCC) in NSCLC specimens obtained via TTNA.
- To assess the feasibility of miRNA profiling for subclassification of NSCLC in challenging, limited sample types.
Main Methods:
- Cytologic and immunocytochemical classification of 31 NSCLC TTNA specimens into AD or SCC.
- Quantification of hsa-let-7 family and hsa-miR-205 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
- Statistical comparison of miRNA expression levels between AD and SCC groups using Student t test.
Main Results:
- Eighteen AD and 13 SCC cases were identified based on morphology and immunocytochemistry.
- Statistically significant differences in miRNA expression were observed between AD and SCC.
- AD specimens showed upregulation of hsa-let-7 family members (hsa-let-7a, b, c, f, g, i) and hsa-miR-98, and downregulation of hsa-miR-205 compared to SCC (P < .05).
Conclusions:
- Profiling the hsa-let-7 family and hsa-miR-205 is a promising approach for distinguishing AD from SCC in NSCLC.
- This miRNA profiling method is effective even with small specimens like those from TTNA.
- Further validation in larger studies could establish this as a reliable tool for NSCLC subclassification.
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