title: Overexpression of PY1289-HER3 in sporadic pulmonary carcinoid from patients bearingMEN1gene variants.
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 withMEN1variants, than in tumors withMEN1wild-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 harboringMEN1gene variants.
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy; Center of Excellence on Aging, University 'G. d'Annunzio' Foundation, I-66010 Chieti, Italy.
authors.forename: Rossano
authors.initials: R
authors.lastname: Lattanzio
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy; Center of Excellence on Aging, University 'G. d'Annunzio' Foundation, I-66010 Chieti, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Veschi
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy.
authors.forename: Gitana Maria
authors.initials: GM
authors.lastname: Aceto
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Curia
authors.affiliation: Department of Pharmacy, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cama
authors.affiliation: Department of Pharmacy, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: DE Lellis
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Fantini
authors.affiliation: Division of Pathology, 'SS Annunziata' Hospital, I-66010 Chieti, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Angelucci
authors.affiliation: Center of Excellence on Aging, University 'G. d'Annunzio' Foundation, I-66010 Chieti, Italy; Mediapharma s.r.l., I-66010 Chieti, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Iacobelli
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy; Center of Excellence on Aging, University 'G. d'Annunzio' Foundation, I-66010 Chieti, Italy; Mediapharma s.r.l., I-66010 Chieti, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Piantelli
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University 'G. d'Annunzio' - Chieti-Pescara, I-66010 Chieti, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Battista
keywords: MEN1; human epidermal growth factor receptors; phosphorylated forms; pulmonary carcinoid