Lung Cancer: Lung Cancer I |

miRNA Profiling of Lung Squamous Cell Carcinoma in the Head and Neck Cancer Patient: Metastasis or Primary Tumor? FREE TO VIEW

Juan Munoz; Praveen Sridhar; Adam Gower; Anita Deshpande; Yuriy Alekseyev; Carl O'Hara; Hiran Fernando; Virginia Litle
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Boston University School of Medicine, Boston, MA

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A286. doi:10.1016/j.chest.2016.02.298
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: Distinguishing between primary lung squamous cell carcinoma (LSCC) and a metastatic lung lesion in a patient with history of head and neck SCC (HNSCC) can be challenging even after pathologic assessment and genetic analysis. Differentiation between these two is essential since this determines the proper therapeutic approach. An accurate diagnosis through miRNA profiling could be useful to discriminate between these two, aiding in the selection of the appropriate surgical resection

METHODS: Specimens of resected primary HNSCC (n=17) and LSCC (n=18) were obtained from formalin-fixed paraffin embedded (FFPE) blocks. Histopathological examination confirmed ≥70% tumor content in all samples. FFPE samples were sectioned and deparaffinized, and total RNA was isolated using the QIAGEN miRNeasy FFPE kit and profiled using Affymetrix miRNA 3.0 arrays. Affymetrix Expression Console was used to generate expression levels and detection (Present/Absent) calls for 1,733 mature human miRNAs in each sample.

RESULTS: Twelve HNSCC and 16 LSCC samples were included for analysis (mean RLE <0.5, >20% miRNAs Present). Of the 690 miRNAs present in ≥25% of samples, 48 were differentially expressed (Student p<0.05) between HNSCC and LSCC. Notably, six miRNAs (miR-379/411/299/381/134/409) located within a ∼40kb region of chromosome 14 were coordinately up-regulated in HNSCC. Interestingly, the ratio of miR-10a and -10b, which are highly conserved, nearly identical, and located within clusters of Hox developmental regulators, was associated with primary cancer site: miR-10a expression was higher than that of miR-10b in 15/16 LSCCs, but in just 5/12 HNSCCs.

CONCLUSIONS: The distinction between a primary LSCC and a metastatic lesion in a patient with history of HNSCC is challenging. The differentiation between these two is crucial since this determines the appropriate therapeutic approach. The expression of miRNAs may be useful for discriminating between HNSCC and LSCC, including markers of possible copy number variation at 14q32.31 and the ratio of miR-10a: miR-10b.

CLINICAL IMPLICATIONS: An anatomical resection indicated for primary lung tumors is associated with a higher risk of morbidity and perioperative mortality compared with a non-anatomical (wedge) resection indicated for metastases. In order to guide the appropriate extent of surgical resection in a patient with history of head and neck cancer and a LSCC (either primary lung or metastatic), a method to distinguish primary lung from metastatic lesions would have clinical utility.

DISCLOSURE: The following authors have nothing to disclose: Juan Munoz, Praveen Sridhar, Adam Gower, Anita Deshpande, Yuriy Alekseyev, Carl O'Hara, Hiran Fernando, Virginia Litle

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