Overexpression of PY1289‑HER3 in sporadic pulmonary carcinoid from patients bearing MEN1 gene variants

Lattanzio,Rossano; Veschi,Serena; Aceto,Gitana Maria; Curia,Maria Cristina; Cama,Alessandro; De Lellis,Laura; Fantini,Fabiana; Angelucci,Domenico; Iacobelli,Stefano; Piantelli,Mauro; Battista,Pasquale

doi:10.3892/ol.2016.4651

Overexpression of PY1289‑HER3 in sporadic pulmonary carcinoid from patients bearing MEN1 gene variants

Authors:
- Rossano Lattanzio
- Serena Veschi
- Gitana Maria Aceto
- Maria Cristina Curia
- Alessandro Cama
- Laura De Lellis
- Fabiana Fantini
- Domenico Angelucci
- Stefano Iacobelli
- Mauro Piantelli
- Pasquale Battista
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Affiliations: Department of Medical, Oral and Biotechnological Sciences, University ‘G. d'Annunzio’ - Chieti‑Pescara, I-66010 Chieti, Italy, Department of Pharmacy, University ‘G. d'Annunzio’ - Chieti‑Pescara, I-66010 Chieti, Italy, Division of Pathology, ‘SS Annunziata’ Hospital, I-66010 Chieti, Italy, Center of Excellence on Aging, University ‘G. d'Annunzio’ Foundation, I-66010 Chieti, Italy
Published online on: June 1, 2016 https://doi.org/10.3892/ol.2016.4651
Pages: 453-458
Copyright: © Lattanzio et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the expression of human epidermal growth factor receptors (HERs) (HER1/HER2/HER3/HER4) and their phosphorylated forms (p‑HER1/p‑HER2/p‑HER3/p‑HER4) in pulmonary carcinoids (PCs). HER and p‑HER protein expression was assessed by immunohistochemistry on tissue microarrays in 37 specimens of sporadic PCs, 29 typical carcinoids (TCs) and 8 atypical carcinoids (ACs). When compared with the ACs, the TCs did not exhibit any differences in terms of HER/p‑HER expression. The tumors of this study have previously been characterized for the expression of menin and the mutational status of menin 1 (MEN1), a gene strongly implicated in the pathogenesis of PCs. In the present study, it was found that the cytoplasmic (‘disarrayed’), but not nuclear (‘arrayed’) expression of menin was positively correlated with HER3 (P=0.004), HER4 (P=0.015), p‑HER1 (P=0.005), p‑HER3 (P<0.001), and p‑HER4 (P=0.001) expression. Moreover, HER3 and p‑HER3 were found to be significantly more expressed in PCs with MEN1 variants, than in tumors with MEN1 wild‑type (P=0.000 and P=0.025, respectively). These findings suggest the potential clinical use of HER inhibitors in the treatment of patients with PCs, particularly for individuals with p‑HER3‑positive PCs harboring MEN1 gene variants.

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