In Situ Hybridization Analysis of Long Non-coding RNAs MALAT1 and HOTAIR in Gastroenteropancreatic Neuroendocrine Neoplasms

  • Ying-Hsia Chu
  • Heather Hardin
  • Jens Eickhoff
  • Ricardo V. LloydEmail author


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.


HOTAIR 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.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ying-Hsia Chu
    • 1
  • Heather Hardin
    • 1
  • Jens Eickhoff
    • 2
  • Ricardo V. Lloyd
    • 1
  1. 1.Department of Pathology and Laboratory MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.Department of Biostatistics and Medical InformaticsUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA

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