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Open Access 14-03-2024 | Prolactinoma

Pituitary tumours without distinct lineage differentiation express stem cell marker SOX2

Authors: Nèle F. Lenders, Tanya J. Thompson, Jeanie Chui, Julia Low, Warrick J. Inder, Peter E. Earls, Ann I. McCormack

Published in: Pituitary

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Abstract

Context

The recent WHO 2022 Classification of pituitary tumours identified a novel group of ‘plurihormonal tumours without distinct lineage differentiation (WDLD)’. By definition, these express multiple combinations of lineage commitment transcription factors, in a monomorphous population of cells.

Objectives

To determine the expression of stem cell markers (SOX2, Nestin, CD133) within tumours WDLD, immature PIT-1 lineage and acidophil stem cell tumours, compared with committed cell lineage tumours.

Methods

Retrospective evaluation of surgically resected pituitary tumours from St Vincent’s Hospital, Sydney. Patients were selected to cover a range of tumour types, based on transcription factor and hormone immunohistochemistry. Clinical data was collected from patient files. Radiology reports were reviewed for size and invasion. Samples were analysed by immunohistochemistry and RT-qPCR for SF-1, PIT-1, T-PIT, SOX2, Nestin and CD133. Stem cell markers were compared between tumours WDLD and those with classically “mature” types.

Results

On immunohistochemistry, SOX2 was positive in a higher proportion of tumours WDLD compared with those meeting WHO lineage criteria, 7/10 v 10/42 (70 v 23.4%, p = 0.005). CD133 was positive in 2/10 tumours WDLD but 0/41 meeting lineage criteria, P = 0.003. On RT-qPCR, there was no significant difference in relative expression of stem cell markers (SOX2, CD133, Nestin) between tumours with and WDLD.

Conclusions

Our study is the first to biologically characterise pituitary tumours WDLD. We demonstrate that these tumours exhibit a higher expression of the stem cell marker SOX2 compared with other lineage-differentiated tumours, suggesting possible involvement of stem cells in their development.
Literature
1.
go back to reference Russell JP, Lim X, Santambrogio A, Yianni V, Kemkem Y, Wang B, Fish M, Haston S, Grabek A, Hallang S, Lodge EJ, Patist AL, Schedl A, Mollard P, Nusse R, Andoniadou CL (2021) Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells. Elife 10. https://doi.org/10.7554/eLife.59142 Russell JP, Lim X, Santambrogio A, Yianni V, Kemkem Y, Wang B, Fish M, Haston S, Grabek A, Hallang S, Lodge EJ, Patist AL, Schedl A, Mollard P, Nusse R, Andoniadou CL (2021) Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells. Elife 10. https://​doi.​org/​10.​7554/​eLife.​59142
7.
go back to reference Clayton RN, Pfeifer M, Atkinson AB, Belchetz P, Wass JA, Kyrodimou E, Vanderpump M, Simpson D, Bicknell J, Farrell WE (2000) Different patterns of allelic loss (loss of heterozygosity) in recurrent human pituitary tumors provide evidence for multiclonal origins. Clin Cancer Res 6(10):3973–3982PubMed Clayton RN, Pfeifer M, Atkinson AB, Belchetz P, Wass JA, Kyrodimou E, Vanderpump M, Simpson D, Bicknell J, Farrell WE (2000) Different patterns of allelic loss (loss of heterozygosity) in recurrent human pituitary tumors provide evidence for multiclonal origins. Clin Cancer Res 6(10):3973–3982PubMed
13.
go back to reference Mertens F, Gremeaux L, Chen J, Fu Q, Willems C, Roose H, Govaere O, Roskams T, Cristina C, Becú-Villalobos D, Jorissen M, Poorten VV, Bex M, Loon Jv, Vankelecom H (2015) Pituitary tumors contain a side population with tumor stem cell-associated characteristics. 22(4):481. https://doi.org/10.1530/erc-14-0546 Mertens F, Gremeaux L, Chen J, Fu Q, Willems C, Roose H, Govaere O, Roskams T, Cristina C, Becú-Villalobos D, Jorissen M, Poorten VV, Bex M, Loon Jv, Vankelecom H (2015) Pituitary tumors contain a side population with tumor stem cell-associated characteristics. 22(4):481. https://​doi.​org/​10.​1530/​erc-14-0546
15.
go back to reference Peverelli E, Giardino E, Treppiedi D, Meregalli M, Belicchi M, Vaira V, Corbetta S, Verdelli C, Verrua E, Serban AL, Locatelli M, Carrabba G, Gaudenzi G, Malchiodi E, Cassinelli L, Lania AG, Ferrero S, Bosari S, Vitale G, Torrente Y, Spada A, Mantovani G (2017) Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors. Int J Cancer 140(8):1870–1880. https://doi.org/10.1002/ijc.30613CrossRefPubMed Peverelli E, Giardino E, Treppiedi D, Meregalli M, Belicchi M, Vaira V, Corbetta S, Verdelli C, Verrua E, Serban AL, Locatelli M, Carrabba G, Gaudenzi G, Malchiodi E, Cassinelli L, Lania AG, Ferrero S, Bosari S, Vitale G, Torrente Y, Spada A, Mantovani G (2017) Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors. Int J Cancer 140(8):1870–1880. https://​doi.​org/​10.​1002/​ijc.​30613CrossRefPubMed
17.
go back to reference Zhang Z, Zamojski M, Smith GR, Willis TL, Yianni V, Mendelev N, Pincas H, Seenarine N, Amper MAS, Vasoya M, Cheng WS, Zaslavsky E, Nair VD, Turgeon JL, Bernard DJ, Troyanskaya OG, Andoniadou CL, Sealfon SC, Ruf-Zamojski F (2022) Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms. Cell Rep 38(10):110467. https://doi.org/10.1016/j.celrep.2022.110467CrossRefPubMedPubMedCentral Zhang Z, Zamojski M, Smith GR, Willis TL, Yianni V, Mendelev N, Pincas H, Seenarine N, Amper MAS, Vasoya M, Cheng WS, Zaslavsky E, Nair VD, Turgeon JL, Bernard DJ, Troyanskaya OG, Andoniadou CL, Sealfon SC, Ruf-Zamojski F (2022) Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms. Cell Rep 38(10):110467. https://​doi.​org/​10.​1016/​j.​celrep.​2022.​110467CrossRefPubMedPubMedCentral
18.
go back to reference Lloyd RV, Kloppel OR, Rosai G (2017) J: WHO classification of tumours of endocrine organs, vol 10, 4 edn. IARC, Lyon Lloyd RV, Kloppel OR, Rosai G (2017) J: WHO classification of tumours of endocrine organs, vol 10, 4 edn. IARC, Lyon
24.
go back to reference Torregrosa-Quesada ME, Garcia-Martinez A, Silva-Ortega S, Martinez-Lopez S, Camara R, Fajardo C, Lamas C, Aranda I, Pico A (2019) How Valuable is the RT-qPCR of Pituitary-Specific Transcription Factors for identifying Pituitary neuroendocrine tumor subtypes according to the New WHO 2017 Criteria? Cancers (Basel) 11(12). https://doi.org/10.3390/cancers11121990 Torregrosa-Quesada ME, Garcia-Martinez A, Silva-Ortega S, Martinez-Lopez S, Camara R, Fajardo C, Lamas C, Aranda I, Pico A (2019) How Valuable is the RT-qPCR of Pituitary-Specific Transcription Factors for identifying Pituitary neuroendocrine tumor subtypes according to the New WHO 2017 Criteria? Cancers (Basel) 11(12). https://​doi.​org/​10.​3390/​cancers11121990
29.
go back to reference Richardson TE, Shen ZJ, Kanchwala M, Xing C, Filatenkov A, Shang P, Barnett S, Abedin Z, Malter JS, Raisanen JM, Burns DK, White CL, Hatanpaa KJ (2017) Aggressive behavior in Silent Subtype III Pituitary Adenomas May depend on suppression of local Immune response: a whole transcriptome analysis. J Neuropathol Exp Neurol 76(10):874–882. https://doi.org/10.1093/jnen/nlx072CrossRefPubMed Richardson TE, Shen ZJ, Kanchwala M, Xing C, Filatenkov A, Shang P, Barnett S, Abedin Z, Malter JS, Raisanen JM, Burns DK, White CL, Hatanpaa KJ (2017) Aggressive behavior in Silent Subtype III Pituitary Adenomas May depend on suppression of local Immune response: a whole transcriptome analysis. J Neuropathol Exp Neurol 76(10):874–882. https://​doi.​org/​10.​1093/​jnen/​nlx072CrossRefPubMed
36.
go back to reference Gonzalez-Meljem JM, Haston S, Carreno G, Apps JR, Pozzi S, Stache C, Kaushal G, Virasami A, Panousopoulos L, Mousavy-Gharavy SN, Guerrero A, Rashid M, Jani N, Goding CR, Jacques TS, Adams DJ, Gil J, Andoniadou CL, Martinez-Barbera JP (2017) Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma. Nat Commun 8(1):1819. https://doi.org/10.1038/s41467-017-01992-5ADSCrossRefPubMedPubMedCentral Gonzalez-Meljem JM, Haston S, Carreno G, Apps JR, Pozzi S, Stache C, Kaushal G, Virasami A, Panousopoulos L, Mousavy-Gharavy SN, Guerrero A, Rashid M, Jani N, Goding CR, Jacques TS, Adams DJ, Gil J, Andoniadou CL, Martinez-Barbera JP (2017) Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma. Nat Commun 8(1):1819. https://​doi.​org/​10.​1038/​s41467-017-01992-5ADSCrossRefPubMedPubMedCentral
37.
go back to reference Andoniadou CL, Matsushima D, Mousavy Gharavy SN, Signore M, Mackintosh AI, Schaeffer M, Gaston-Massuet C, Mollard P, Jacques TS, Le Tissier P, Dattani MT, Pevny LH, Martinez-Barbera JP (2013) Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell 13(4):433–445. https://doi.org/10.1016/j.stem.2013.07.004CrossRefPubMed Andoniadou CL, Matsushima D, Mousavy Gharavy SN, Signore M, Mackintosh AI, Schaeffer M, Gaston-Massuet C, Mollard P, Jacques TS, Le Tissier P, Dattani MT, Pevny LH, Martinez-Barbera JP (2013) Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell 13(4):433–445. https://​doi.​org/​10.​1016/​j.​stem.​2013.​07.​004CrossRefPubMed
38.
go back to reference Mertens F, Gremeaux L, Chen J, Fu Q, Willems C, Roose H, Govaere O, Roskams T, Cristina C, Becu-Villalobos D, Jorissen M, Poorten VV, Bex M, van Loon J, Vankelecom H (2015) Pituitary tumors contain a side population with tumor stem cell-associated characteristics. Endocr Relat Cancer 22(4):481–504. https://doi.org/10.1530/ERC-14-0546CrossRefPubMed Mertens F, Gremeaux L, Chen J, Fu Q, Willems C, Roose H, Govaere O, Roskams T, Cristina C, Becu-Villalobos D, Jorissen M, Poorten VV, Bex M, van Loon J, Vankelecom H (2015) Pituitary tumors contain a side population with tumor stem cell-associated characteristics. Endocr Relat Cancer 22(4):481–504. https://​doi.​org/​10.​1530/​ERC-14-0546CrossRefPubMed
39.
go back to reference Hickman RA, Bruce JN, Otten M, Khandji AG, Flowers XE, Siegelin M, Lopes B, Faust PL, Freda PU (2021) Gonadotroph tumours with a low SF-1 labelling index are more likely to recur and are associated with enrichment of the PI3K-AKT pathway. Neuropathol Appl Neurobiol 47(3):415–427. https://doi.org/10.1111/nan.12675CrossRefPubMed Hickman RA, Bruce JN, Otten M, Khandji AG, Flowers XE, Siegelin M, Lopes B, Faust PL, Freda PU (2021) Gonadotroph tumours with a low SF-1 labelling index are more likely to recur and are associated with enrichment of the PI3K-AKT pathway. Neuropathol Appl Neurobiol 47(3):415–427. https://​doi.​org/​10.​1111/​nan.​12675CrossRefPubMed
40.
go back to reference Chang CV, Araujo RV, Cirqueira CS, Cani CM, Matushita H, Cescato VA, Fragoso MC, Bronstein MD, Zerbini MC, Mendonca BB, Carvalho LR (2017) Differential expression of stem cell markers in Human Adamantinomatous Craniopharyngioma and Pituitary Adenoma. Neuroendocrinology 104(2):183–193. https://doi.org/10.1159/000446072CrossRefPubMed Chang CV, Araujo RV, Cirqueira CS, Cani CM, Matushita H, Cescato VA, Fragoso MC, Bronstein MD, Zerbini MC, Mendonca BB, Carvalho LR (2017) Differential expression of stem cell markers in Human Adamantinomatous Craniopharyngioma and Pituitary Adenoma. Neuroendocrinology 104(2):183–193. https://​doi.​org/​10.​1159/​000446072CrossRefPubMed
41.
go back to reference Choi H, Kim Y, Kang D, Kwon A, Kim J, Kim M, Park J, Kim SS, Min YJ, Kim CK (2020) Common and different alterations of bone marrow mesenchymal stromal cells in myelodysplastic syndrome and multiple myeloma. Cell Prolif 53(5). https://doi.org/10.1111/cpr.12819. e12819 Choi H, Kim Y, Kang D, Kwon A, Kim J, Kim M, Park J, Kim SS, Min YJ, Kim CK (2020) Common and different alterations of bone marrow mesenchymal stromal cells in myelodysplastic syndrome and multiple myeloma. Cell Prolif 53(5). https://​doi.​org/​10.​1111/​cpr.​12819. e12819
42.
go back to reference Virant-Klun I, Skerl P, Novakovic S, Vrtacnik-Bokal E, Smrkolj S (2019) Similar Population of CD133 + and DDX4 + VSEL-Like Stem cells sorted from human embryonic stem cell, ovarian, and ovarian Cancer ascites cell cultures. Real Embryonic Stem Cells? Cells 8(7). https://doi.org/10.3390/cells8070706 Virant-Klun I, Skerl P, Novakovic S, Vrtacnik-Bokal E, Smrkolj S (2019) Similar Population of CD133 + and DDX4 + VSEL-Like Stem cells sorted from human embryonic stem cell, ovarian, and ovarian Cancer ascites cell cultures. Real Embryonic Stem Cells? Cells 8(7). https://​doi.​org/​10.​3390/​cells8070706
Metadata
Title
Pituitary tumours without distinct lineage differentiation express stem cell marker SOX2
Authors
Nèle F. Lenders
Tanya J. Thompson
Jeanie Chui
Julia Low
Warrick J. Inder
Peter E. Earls
Ann I. McCormack
Publication date
14-03-2024
Publisher
Springer US
Keyword
Prolactinoma
Published in
Pituitary
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-024-01385-0
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