E-cadherin expression and gene expression profiles in corticotroph pituitary neuroendocrine tumor subtypes

Author:

Kiseljak-Vassiliades Katja12ORCID,Lipe Kristin13,Turin Christie G1,Fishbein Lauren124ORCID,Costello James C56,Kerr Janice M1,Holmstoen Tessa B1,Youssef A Samy7,Lillehei Kevin O7,Kleinschmidt-DeMasters Bette K789,Wierman Margaret E12

Affiliation:

1. Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Colorado Anschutz Medical Campus , Aurora, Colorado, USA

2. Section of Endocrinology, Department of Medicine, Research Service at Rocky Mountain Regional Veterans Affairs Medical Center , Aurora, Colorado, USA

3. Department of Surgery, Good Samaritan Regional Medical Center , Corvallis, Oregon, USA

4. Department of Biomedical Informatics, University of Colorado School of Medicine, Colorado Anschutz Medical Campus , Aurora, Colorado, USA

5. Department of Pharmacology, University of Colorado School of Medicine, Colorado Anschutz Medical Campus , Aurora, Colorado, USA

6. University of Colorado Cancer Center, University of Colorado School of Medicine, Colorado Anschutz Medical Campus , Aurora, Colorado, USA

7. Department of Neurosurgery, University of Colorado School of Medicine, Colorado Anschutz Medical Campus , Aurora, Colorado, USA

8. Department of Pathology, University of Colorado School of Medicine, Colorado Anschutz Medical Campus , Aurora, Colorado, USA

9. Department of Neurology, University of Colorado School of Medicine, Colorado Anschutz Medical Campus , Aurora, Colorado, USA

Abstract

Abstract Corticotroph adenomas/pituitary neuroendocrine tumors (PitNETs) are associated with significant morbidity and mortality. Predictors of tumor behavior have not shown high prognostic accuracy. For somatotroph adenomas/PitNETs, E-cadherin expression correlates strongly with prognosis. E-cadherin expression has not been investigated in other PitNETs. A retrospective chart review of adults with corticotroph adenomas/PitNETs was conducted to assess correlation between E-cadherin expression and tumor characteristics. In addition, gene expression microarray was performed in subset of tumors (n = 16). Seventy-seven patients were identified; 71% were female, with median age of cohort 45.2 years. Seventy-five percent had macroadenomas, of which 22% were hormonally active. Ninety-five percent of microadenomas were hormonally active. Adrenocorticotropic hormone granulation pattern by IHC identified 63% as densely granulated (DG) and 34% as sparsely granulated (SG). All microadenomas were DG (p < .001); 50% of macroadenomas were DG associated with increased tumor invasion compared to SG. E-cadherin IHC was positive in 80%, diminished in 17%, and absent in 20% and did not correlate with corticotroph PitNETs subtype, size, or prognosis. In contrast to the distinct transcriptomes of corticotroph PitNETs and normal pituitaries, a comparison of clinically active and silent corticotroph PitNETs demonstrated similar molecular signatures indicating their common origin, but with unique differences related to their secretory status.

Funder

Biostatistics and Bioinformatics Shared Resource

Publisher

Oxford University Press (OUP)

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