Analysis of miR-96 and miR-133a Expression in Gastrointestinal Neuroendocrine Neoplasms
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Grading of gastrointestinal neuroendocrine neoplasms (GI-NENs) relies mainly on mitotic activity and Ki-67 proliferation index. It is often difficult to predict metastatic potential of these neoplasms. Recent studies have shown that GI-NENs express a wide spectrum of microRNAs. We examined two microRNAs (miR-96 and miR-133a) that were recently identified in GI-NENs to determine if they could assist in evaluating the biological behavior of these neoplasms. A tissue microarray (TMA) was constructed with 51 primary GI-NENs, mainly from the small intestine and metastatic tumors from the same cases, including liver metastases (N = 20) and lymph node metastases (N = 33). The cases were immunohistochemically stained for chromogranin A, synaptophysin, and Ki-67. In situ hybridization (ISH) was done with probes from Exiqon (Woburn, MA). Quantitative RT-PCR (qRT-PCR) was also performed on all the cases (N = 105). ISH analysis showed that miR-96 expression was significantly higher in the liver metastatic neoplasms compared to the primary NENs (p < 0.05); however, it was not significant for miR-133a expression levels. qRT-PCR showed that miR-96 levels were increased during progression from the primary tumors to metastases in the liver. qRT-PCR showed a decrease in miR-133a in the liver metastases compared to the primary tumors (p < 0.05). Appendiceal carcinoids without metastases (n = 3) had low levels of miR-96 and high levels of miR-133a by qPCR. The study suggests that analysis of these two microRNAs by qRT-PCR may be useful in detecting more aggressive GI-NENs and that ISH analysis may also assist in the evaluation of patients with GI-NENs.
KeywordsmiR-96 miR-133a Gastrointestinal neuroendocrine neoplasm In situ hybridization Carcinoid
This research project was supported by the Department of Pathology Research Fund from the University of Wisconsin School of Medicine and Public Health (to RM).
The authors thank the University of Wisconsin Translational Research Initiatives in Pathology laboratory, in part supported by the UW Department of Pathology and Laboratory Medicine and UWCCC grant P30 CA014520-39, for use of its facilities and services.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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