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Minerva Endocrinologica 2019 June;44(2):129-36

DOI: 10.23736/S0391-1977.18.02933-4


lingua: Inglese

Pathological markers of somatotroph pituitary neuroendocrine tumors predicting the response to medical treatment

Jacqueline TROUILLAS 1, 2, Alexandre VASILJEVIC 1, 2, 3, 4, Marion LAPOIRIE 1, 2, 5, Laura CHINEZU 6, Emmanuel JOUANNEAU 1, 2, 4, 7, Gérald RAVEROT 1, 2, 4, 5

1 University of Lyon 1, Lyon, France; 2 Faculty of Medicine Lyon-Est, University of Lyon 1, Lyon, France; 3 Centre de Pathologie et de Neuropathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; 4 Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR5286, University of Lyon, Lyon, France; 5 Federation of Endocrinology, Reference Center for Rare Pituitary Diseases, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; 6 Department of Histology, University of Medicine, Pharmacy, Sciences and Technology of Tirgu Mures, Tirgu Mures, Romania; 7 Unit of Neurosurgery, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France

Acromegaly is mainly due to the somatotroph pituitary neuroendocrine tumors (PitNET)s. These have been subtyped into densely granulated (DG) and sparsely granulated (SG) tumors, which differ in clinical, histological and biological characteristics and in response to somatostatin analogs (SA)s. The variable remission rate after surgical resection, as first line treatment, has increased interest in identifying pathological markers to better predict the response to medical treatment. Several techniques have shown somatotroph tumors to express somatostatin receptors (SSTR)s, and mainly SSTR2 and SSTR5. The molecular methods appear to give contradictory results, are expansive and cannot be routinely performed. Immunohistochemistry, while being the most powerful technique, requires optimal fixation and the use of monoclonal antibodies against at least SSTR2 and SSTR5. Almost all somatotroph tumors express SSTR2 or SSTR5, and, in great majority, at a high level. More importantly, the type of SSTR, the level of expression, and the response to SA treatment appear well correlated. Indeed, a significantly higher expression of SSTR2 in DG compared to in SG tumors likely explains the better response of DG tumors to the normalization of growth hormone and insulin-like growth factor-1 under SA. However, a reproducible scoring and a cut-off from which the SA efficacy can be reliably predicted, remain to be found. In conclusion, the SSTR expression profile and morphological subtypes of the somatotroph tumor may help predict the response to medical treatment. Such pathological profiling could become a useful decision-making tool for clinicians in the context of a multidisciplinary approach, after surgery failure.

KEY WORDS: Pituitary neoplasms - Growth hormone-secreting pituitary adenoma - Acromegaly

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