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      Predictive and prognostic significance of tumour subtype, SSTR1‐5 and e‐cadherin expression in a well‐defined cohort of patients with acromegaly

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          Abstract

          In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1‐5, dopamine D2 receptor, E‐cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E‐cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E‐cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E‐cadherin was observed when tumour subtype was considered . Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.

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          Proteomics. Tissue-based map of the human proteome.

          Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. Copyright © 2015, American Association for the Advancement of Science.
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            A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

            Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
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              From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

              The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.
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                Author and article information

                Contributors
                gabalecf@fhk.cuni.cz
                Journal
                J Cell Mol Med
                J Cell Mol Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                24 January 2021
                March 2021
                : 25
                : 5 ( doiID: 10.1111/jcmm.v25.5 )
                : 2484-2492
                Affiliations
                [ 1 ] The Fingerland Department of Pathology Faculty of Medicine University Hospital Charles University Hradec Kralove Czech Republic
                [ 2 ] Department of Pathology Faculty of Medicine Charles University Plzen Czech Republic
                [ 3 ] Bioptical Laboratory, Ltd. Plzen Czech Republic
                [ 4 ] Department of Pathology Military University Hospital Prague Prague Czech Republic
                [ 5 ] Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Králové Charles University Hradec Kralove Czech Republic
                [ 6 ] Department of Medical Biology and Genetics Faculty of Medicine Hradec Kralove Charles University Hradec Kralove Czech Republic
                [ 7 ] Department of Neurosurgery Faculty of Medicine University Hospital Charles University Hradec Kralove Czech Republic
                [ 8 ] Department of Neurosurgery and Neurooncology 1st Medical Faculty Charles University Military University Hospital Prague Prague Czech Republic
                [ 9 ] 4th Department of Internal medicine Faculty of Medicine University Hospital Charles University Hradec Kralove Czech Republic
                [ 10 ] 3rd Department of Internal Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic
                [ 11 ] 1st Department of Internal Medicine Faculty of Medicine in Pilsen University Hospital Pilsen Charles University Pilsen Czech Republic
                [ 12 ] 1st Internal Clinic Louis Pasteur University Hospital Kosice Slovakia
                [ 13 ] 2nd Department of Internal Medicine Faculty of Medicine St. Ann University Hospital Brno Masaryk University Brno Brno Czech Republic
                [ 14 ] Department of Internal Medicine and Gastroenterology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic
                [ 15 ] National Institute of Endocrinology and Diabetology Lubochňa Slovakia
                Author notes
                [*] [* ] Correspondence

                Filip Gabalec, 4th Department of Internal Medicine, University Hospital Hradec Kralove, Sokolska 581, 50005 Hradec Králové, Czech Republic.

                Email: gabalecf@ 123456fhk.cuni.cz

                Author information
                https://orcid.org/0000-0002-7053-3369
                Article
                JCMM16173
                10.1111/jcmm.16173
                7933931
                33491286
                809ef0f3-fc71-4fbf-8487-275fc6254964
                © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 September 2020
                : 29 October 2020
                : 21 November 2020
                Page count
                Figures: 4, Tables: 2, Pages: 9, Words: 6289
                Funding
                Funded by: Ministerstvo Zdravotnictví Ceské Republiky , open-funder-registry 10.13039/501100003243;
                Award ID: NV19‐01‐00435
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                March 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.9 mode:remove_FC converted:05.03.2021

                Molecular medicine
                acromegaly,pitnet,pituitary neoplasm,somatostatin receptor
                Molecular medicine
                acromegaly, pitnet, pituitary neoplasm, somatostatin receptor

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