Differential Expression of microRNA Markers in Pulmonary Neuroendocrine Tumors: Correlation with Histologic Grade.
Mee Sook Roh, Chang Hun Lee, Hee Kyung Chang, Sunhee Chang, Seung Yeon Ha, Kun Young Kwon, Il Seon Hwang, Hyoun Wook Lee, Eun Hee Lee. Dong-A University, Busan, Republic of Korea; Busan National University, Republic of Korea; Kosin University, Busan, Republic of Korea; Inje University Ilsan Paik Hospital, Ilsan, Republic of Korea; Gachon University of Medicine and Science, Incheon, Republic of Korea; Keimyung University, Daegu, Republic of Korea; Samsung Changwon Medical Center, Changwon, Republic of Korea
Background: Pulmonary neuroendocrine (NE) tumors include low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC) and high-grade large cell NE carcinoma (LCNEC) and small cell lung carcinoma (SCLC). These tumors have been a difficult challenge for pathologists to diagnose. MicroRNAs (miRNAs) have a critical effect on carcinogenesis through post-transcriptional modification and are considered as potential biomarkers for cancer diagnosis.
Design: The expression of five selected miRNA (miR-21, miR-34, miR-135, miR-155, and let 7a) was evaluated in 60 pulmonary NE tumor tissues (18 TCs, 6 ACs, 21 LCNECs and 15 SCLCs) to explore whether the differential expression of miRNAs can be used as a diagnostic tool in grading pulmonary NE tumors. Total RNA was extracted from formalin-fixed paraffin-embedded tissue using RecoverAll Total Nucleic Acid Isolation kit. Quantitative RT-PCR for each miRNA species was performed using the miRNA TagMan RT-PCR kit. Control amplification for endogenous small RNA U6 was performed in all samples. Mean Ct values were calculated for each case and then normalized against the corresponding U6 Ct values, calculated as (Ctexperimental miRNA-Ctu6 RNA). The fold differences in miRNA levels between groups were also noted (2ΔCt).
Results: Significant overexpression of miR-21 and miR-155 was found in high-grade NE tumors compared to carcinoid tumors, with mean fold difference ranging from 1.6 to 7.8. Although high-grade NE tumors tended to show lower expression of let-7a than in carcinoid tumors, no significant difference was found (p=0.08). No difference was found between LCNEC and SCLC and between TC and AC for miR-21, miR-155, and let-7a, respectively. In contrast, no significant difference was seen for miR-34 and miR-135 (p=0.12 and 0.64, respectively).
Conclusions: To the best of our knowledge, this is the first study to evaluate miRNA expression pattern in pulmonary NE tumors. We concluded that miRNAs, particularly miR-21 and miR-155, might potentially be adjunct markers for distinguishing high-grade NE tumors from carcinoid tumors. Further miRNA-based approach with a large number of cases would allow us to identify novel miRNA for accurate classification of pulmonary NE tumors.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 250, Wednesday Morning