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Journal of Histochemistry and Cytochemistry
Volume 52 (2): 217-225, 2004
Copyright ©The Histochemical Society, Inc.

Localization of Inhibins and Activins in Normal Endocrine Cells and Endocrine Tumors of the Gut and Pancreas : an Immunohistochemical and In Situ Hybridization Study

Stefano La Rosa, Silvia Uccella, Silvia Marchet, Carlo Capella and Ricardo V. Lloyd

Department of Pathology, Ospedale di Circolo (SLR); Department of Clinical and Biological Sciences, University of Insubria (SU,SM,CC), Varese, Italy; and Department of Laboratory Medicine and Pathology, Mayo Clinic (RVL), Rochester, Minnesota

Correspondence to: Prof. Carlo Capella, Servizio di Anatomia Patologica, Ospedale di Circolo, Viale Borri 57, I-21100 Varese, Italy. E-mail: carlo.capella{at}ospedale.varese.it

Activins and inhibins, which belong to the TGFß family, are composed of different combinations of {alpha}-, ßA-, and ßB-subunits, resulting in inhibin A ({alpha}ßA), inhibin B ({alpha}ßB), activin A (ßAßA), activin B (ßBßB), and activin AB (ßAßB). They regulate several cell functions, acting as paracrine/autocrine factors. Their actions, which depend on binding to specific receptors, are also modulated by follistatin. Gastroenteropancreatic (GEP) endocrine cells and endocrine tumors (ETs) produce several growth factors, but it is not well known whether they express follistatin and the various inhibin/activin subunits. We studied their expression in 65 GEP ETs using immunohistochemistry (IHC) and in situ hybridization (ISH). The {alpha}-subunit and follistatin were not identified in normal GEP endocrine cells and were poorly expressed in ETs. A ßA-subunit immunoreactivity (IR) was detected in A-, G-, EC-, and GIP-cells, while ßB-chain IR was present only in D-cells. The mRNAs encoding for these molecules were poorly expressed in normal tissues. ßA- and ßB-subunits were identified in several ETs by both IHC and ISH: ßA-subunit mainly in G-cell and A-cell ETs, and ßB-subunit in D-cell, A-cell, and EC-cell ETs. Our results demonstrate a differential expression of activin/inhibin subunits among different types of GEP endocrine cells and related tumors, suggesting a role in modulation of biological functions of these normal and neoplastic endocrine cells. (J Histochem Cytochem 52:217–225, 2004)

Key Words: inhibin • activin • immunohistochemistry • in situ hybridization • endocrine tumor • gut • pancreas • localization


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