In Situ Hybridization Analysis of Long Non-coding RNAs MALAT1 and HOTAIR in Gastroenteropancreatic Neuroendocrine Neoplasms
- 52 Downloads
Recent studies suggest onco-regulatory roles for two long non-coding RNAs (lncRNAs), MALAT1 and HOTAIR, in various malignancies; however, these lncRNAs have not been previously examined in neuroendocrine neoplasms (NENs) of gastroenteropancreatic origins (GEP-NENs). In this study, we evaluated the expressions and prognostic significance of MALAT1 and HOTAIR in 83 cases of GEP-NENs (60 grade 1, 17 grade 2, and 6 grade 3 tumors) diagnosed during the years 2005–2017. Expression levels of MALAT1 and HOTAIR were digitally quantitated in assembled tissue microarray slides labeled by chromogenic in situ hybridization (ISH) using InForm 1.4.0 software. We found diffuse nuclear expression of both HOTAIR and MALAT1 in all primary tumors of GEP-NENs with variable intensities. By multivariate model which adjusted for age and histologic grade, high expression of HOTAIR was associated with lower presenting T and M stages and subsequent development of metastases (P < 0.05). MALAT1 expression was associated with presenting T stage and development of metastases (P < 0.05). In summary, MALAT1 and HOTAIR are commonly expressed in GEP-NENs. High expression of either lncRNA showed grade-independent associations with clinically less aggressive disease.
KeywordsHOTAIR MALAT1 Gastroenteropancreatic neuroendocrine neoplasms siRNA Proliferation Invasion
The authors thank the University of Wisconsin Translational Research Initiatives in Pathology Laboratory, in part supported by the University of Wisconsin Department of Pathology and Laboratory Medicine and University of Wisconsin Carbone Cancer Center grant P30 CA014520, for use of its facilities and services.
Dr. Chu and Dr. Lloyd received a Research and Development Award from the Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics to conduct the study.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that there are no conflicts of interest.
- 1.Ohike N, Adsay NV, La Rosa S, Volante M, Zamboni G. 2017. WHO Classification of Tumours of Endocrine Organs, 10 ed. WHO Press, World Health Organization, Geneva.Google Scholar
- 30.Ji S, Qin Y, Shi S, Liu X., Hu H., Zhou H., Gao J., Zhang B., Xu W., Liu J., Liang D., Liu L., Liu C., Long J., Zhou H., Chiao P.J., Xu J., Ni Q., Gao D., Yu X. 2015. ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer. Cell Res 25:561–573.CrossRefGoogle Scholar
- 35.Vijayvergia N, Boland PM, Handorf E, Gustafson KS, Gong Y, Cooper HS, Sheriff F, Astsaturov I, Cohen SJ, Engstrom PF 2016. Molecular profiling of neuroendocrine malignancies to identify prognostic and therapeutic markers: a Fox Chase Cancer Center Pilot Study. Br J Cancer 115:564–570.CrossRefGoogle Scholar
- 39.Mukhopadhyay S, Dermawan JK, Lanigan CP, Farver CF. 2018. Insulinoma-associated protein 1 (INSM1) is a sensitive and highly specific marker of neuroendocrine differentiation in primary lung neoplasms: an immunohistochemical study of 345 cases, including 292 whole-tissue sections. Mod Pathol https://doi.org/10.1038/s41379-018-0122-7.
- 42.Tanigawa M, Nakayama M, Taira T, Hattori S, Mihara Y, Kondo R, Kusano H, Nakamura K, Abe Y, Ishida Y, Okabe Y, Hisaka T, Okuda K, Fujino K, Ito T, Kawahara A, Naito Y, Yamaguchi R, Akiba J, Akagi Y, Yano H 2018. Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor. Med Mol Morphol 51:32–40.CrossRefGoogle Scholar