Intratumoural Spatial Distribution of S100B + folliculostellate Cells is Associated with Proliferation and Expression of FSH and ERα in Gonadotroph Tumours

Overview

Journal Acta Neuropathol Commun

Publisher Biomed Central

Specialty Neurology

Date 2022 Feb 10

PMID 35139928

Authors

Mirela Diana Ilie

Alexandre Vasiljevic

Marie Chanal

Nicolas Gadot

Laura Chinezu

Emmanuel Jouanneau

Ana Hennino

Gerald Raverot

Philippe Bertolino

Affiliations

Soon will be listed here.

Abstract

Folliculostellate cells are S100B-expressing cells with numerous functions in the normal anterior pituitary. These cells have also been identified in pituitary neuroendocrine tumours (PitNETs), where their precise role remains elusive. Here, we aimed to build a refined cartography of S100B-expressing cells to characterise their interpatient and intratumoural spatial distribution, and to start identifying their potential functions in PitNETs. High-throughput histological analysis of S100B-stained tumour sections of 54 PitNETs revealed a significant decrease in S100B + cells in PitNETs compared to the normal anterior pituitary. A Ki67 index ≥ 3, a mitosis count > 2/10 per high power fields, and a proliferative status, were all associated with fewer S100B + cells in gonadotroph tumours. Gonadotroph tumours also showed interpatient and intratumoural heterogeneity in the spatial distribution of S100B + cells. The existence of an intratumoural heterogeneity was further confirmed by the incorporation to our spatial analysis of additional markers: Ki67, FSH, LH, ERα and SSTR2. The tumour areas with fewer S100B + cells displayed a higher percentage of Ki67 + cells, whereas strong positive correlations were observed between S100B + , FSH + , and ERα + cells. Such spatial associations suggest that S100B + folliculostellate cells could play a role in gonadotroph tumorigenesis, and may contribute to the maintenance of tumour cells in a low proliferating, FSH + /ERα + differentiated state. Albeit, further in-depth functional studies are required to decipher the mechanisms underlying these spatial associations and to potentially identify a therapeutic use.

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References

Hickman R, Bruce J, Otten M, Khandji A, Flowers X, Siegelin M . 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. 2020; 47(3):415-427. PMC: 7987644. DOI: 10.1111/nan.12675. View

Friend K, Chiou Y, Lopes M, Laws Jr E, HUGHES K, Shupnik M . Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas. J Clin Endocrinol Metab. 1994; 78(6):1497-504. DOI: 10.1210/jcem.78.6.7515390. View

Pavlovic M, Jovanovic I, Ugrenovic S, Vasovic L, Krstic M, Bakic M . Morphometric analysis of the human anterior pituitary's folliculostellate cells during the aging process. Ann Anat. 2013; 195(3):231-7. DOI: 10.1016/j.aanat.2012.11.002. View

Nishioka H, Inoshita N, Mete O, Asa S, Hayashi K, Takeshita A . The Complementary Role of Transcription Factors in the Accurate Diagnosis of Clinically Nonfunctioning Pituitary Adenomas. Endocr Pathol. 2015; 26(4):349-55. DOI: 10.1007/s12022-015-9398-z. View

Ilie M, Raverot G . Treatment Options for Gonadotroph Tumors: Current State and Perspectives. J Clin Endocrinol Metab. 2020; 105(10). DOI: 10.1210/clinem/dgaa497. View

Asa S, Ezzat S . Aggressive Pituitary Tumors or Localized Pituitary Carcinomas: Defining Pituitary Tumors. Expert Rev Endocrinol Metab. 2018; 11(2):149-162. DOI: 10.1586/17446651.2016.1153422. View

Denef C . Paracrinicity: the story of 30 years of cellular pituitary crosstalk. J Neuroendocrinol. 2007; 20(1):1-70. PMC: 2229370. DOI: 10.1111/j.1365-2826.2007.01616.x. View

Liu J, Dang H, Wang X . The significance of intertumor and intratumor heterogeneity in liver cancer. Exp Mol Med. 2018; 50(1):e416. PMC: 5992990. DOI: 10.1038/emm.2017.165. View

Raverot G, Ilie M, Lasolle H, Amodru V, Trouillas J, Castinetti F . Aggressive pituitary tumours and pituitary carcinomas. Nat Rev Endocrinol. 2021; 17(11):671-684. DOI: 10.1038/s41574-021-00550-w. View

10.

Renner U, Gloddek J, Pereda M, Arzt E, Stalla G . Regulation and role of intrapituitary IL-6 production by folliculostellate cells. Domest Anim Endocrinol. 1998; 15(5):353-62. DOI: 10.1016/s0739-7240(98)00027-7. View

11.

Bilezikjian L, Justice N, Blackler A, Wiater E, Vale W . Cell-type specific modulation of pituitary cells by activin, inhibin and follistatin. Mol Cell Endocrinol. 2012; 359(1-2):43-52. PMC: 3367026. DOI: 10.1016/j.mce.2012.01.025. View

12.

Hofler H, Walter G, Denk H . Immunohistochemistry of folliculo-stellate cells in normal human adenohypophyses and in pituitary adenomas. Acta Neuropathol. 1984; 65(1):35-40. DOI: 10.1007/BF00689825. View

13.

Grzywa T, Paskal W, Wlodarski P . Intratumor and Intertumor Heterogeneity in Melanoma. Transl Oncol. 2017; 10(6):956-975. PMC: 5671412. DOI: 10.1016/j.tranon.2017.09.007. View

14.

Ueta Y, Levy A, Chowdrey H, Lightman S . S-100 antigen-positive folliculostellate cells are not the source of IL-6 gene expression in human pituitary adenomas. J Neuroendocrinol. 1995; 7(6):467-74. DOI: 10.1111/j.1365-2826.1995.tb00783.x. View

15.

Devnath S, Inoue K . An insight to pituitary folliculo-stellate cells. J Neuroendocrinol. 2008; 20(6):687-91. DOI: 10.1111/j.1365-2826.2008.01716.x. View

16.

Kokoris J, Jovanovic I, Pantovic V, Krstic M, Stanojkovic M, Milosevic V . Morphometric analysis of the folliculostellate cells and luteinizing hormone gonadotropic cells of the anterior pituitary of the men during the aging process. Tissue Cell. 2016; 49(1):78-85. DOI: 10.1016/j.tice.2016.11.006. View

17.

Iwaki T, Kondo A, Takeshita I, Nakagaki H, Kitamura K, Tateishi J . Proliferating potential of folliculo-stellate cells in human pituitary adenomas. Immunohistochemical and electron microscopic analysis. Acta Neuropathol. 1986; 71(3-4):233-42. DOI: 10.1007/BF00688045. View

18.

Hui L, Chen Y . Tumor microenvironment: Sanctuary of the devil. Cancer Lett. 2015; 368(1):7-13. DOI: 10.1016/j.canlet.2015.07.039. View

19.

Hodson D, Legros C, Desarmenien M, Guerineau N . Roles of connexins and pannexins in (neuro)endocrine physiology. Cell Mol Life Sci. 2015; 72(15):2911-28. PMC: 5658480. DOI: 10.1007/s00018-015-1967-2. View

20.

Allaerts W, Vankelecom H . History and perspectives of pituitary folliculo-stellate cell research. Eur J Endocrinol. 2005; 153(1):1-12. DOI: 10.1530/eje.1.01949. View