Skip to main content
Erschienen in: Endocrine 2/2018

26.07.2018 | Endocrine Surgery

The role of E and N-cadherin in the postoperative course of gonadotroph pituitary tumours

Erschienen in: Endocrine | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Gonadotroph tumours are the most abundant of the clinically silent pituitary tumours. There is a lack of reliable prognostic markers predicting their clinical course. Our aim was to determine the level of E-cadherin and N-cadherin in a cohort of clinically silent gonadotroph pituitary tumours, and compare them to the rate of reintervention.

Methods

Tumour tissue from primary surgery was retrospectively investigated and compared with clinical data. Immunohistochemical (N = 105) and real time-qPCR (N = 85) analyses for the levels of N-cadherin and the extra- and intracellular domains of E-cadherin were performed. The immunoreactive scores (IRS) and mRNA relative quantity were compared to the rate of reintervention.

Results

The tumours presented a high IRS for N-cadherin (Median 12 (IQR 12-12)) and almost no immunoreactivity for the extracellular domain of E-cadherin (Median 0 (IQR 0-0)). The membranous staining for the intracellular domain of E-cadherin varied (Median 6 (IQR 4-6). Reduced membranous expression of the intracellular domain of E-cadherin was associated with nuclear presence of the same domain. Nuclear staining for the intracellular domain of E-cadherin was associated with a lower rate of reintervention (p = 0.01).

Conclusion

We found that silent gonadotroph tumours presented high IRS for N-cadherin and low IRS for the extracellular domain of E-cadherin. A substantial proportion of the tumours presented nuclear staining for the intracellular domain of E-cadherin, accompanied by a reduced membranous expression of the intracellular domain of E-cadherin. Absence of nuclear staining for the intracellular domain of E-cadherin served as an independent predictor of reintervention.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat S.L. Asa, O. Casar-Borota, P. Chanson, E. Delgrange, P. Earls, S. Ezzat, A. Grossman, H. Ikeda, N. Inoshita, N. Karavitaki, M. Korbonits, E.R. Laws Jr., M.B. Lopes, N. Maartens, I.E. McCutcheon, O. Mete, H. Nishioka, G. Raverot, F. Roncaroli, W. Saeger, L.V. Syro, A. Vasiljevic, C. Villa, A. Wierinckx, J. Trouillas, From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal. Endocr. Relat. Cancer 24(4), C5–c8 (2017). https://doi.org/10.1530/erc-17-0004 CrossRefPubMed S.L. Asa, O. Casar-Borota, P. Chanson, E. Delgrange, P. Earls, S. Ezzat, A. Grossman, H. Ikeda, N. Inoshita, N. Karavitaki, M. Korbonits, E.R. Laws Jr., M.B. Lopes, N. Maartens, I.E. McCutcheon, O. Mete, H. Nishioka, G. Raverot, F. Roncaroli, W. Saeger, L.V. Syro, A. Vasiljevic, C. Villa, A. Wierinckx, J. Trouillas, From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal. Endocr. Relat. Cancer 24(4), C5–c8 (2017). https://​doi.​org/​10.​1530/​erc-17-0004 CrossRefPubMed
4.
Zurück zum Zitat A. Tjornstrand, K. Gunnarsson, M. Evert, E. Holmberg, O. Ragnarsson, T. Rosen, H. Filipsson Nystrom, The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011. Eur. J. Endocrinol. / Eur. Fed. Endocr. Soc. 171(4), 519–526 (2014). https://doi.org/10.1530/eje-14-0144 CrossRef A. Tjornstrand, K. Gunnarsson, M. Evert, E. Holmberg, O. Ragnarsson, T. Rosen, H. Filipsson Nystrom, The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011. Eur. J. Endocrinol. / Eur. Fed. Endocr. Soc. 171(4), 519–526 (2014). https://​doi.​org/​10.​1530/​eje-14-0144 CrossRef
5.
Zurück zum Zitat T.T. Agustsson, T. Baldvinsdottir, J.G. Jonasson, E. Olafsdottir, V. Steinthorsdottir, G. Sigurdsson, A.V. Thorsson, P.V. Carroll, M. Korbonits, R. Benediktsson, The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur. J. Endocrinol. / Eur. Fed. Endocr. Soc. 173(5), 655–664 (2015). https://doi.org/10.1530/eje-15-0189 CrossRef T.T. Agustsson, T. Baldvinsdottir, J.G. Jonasson, E. Olafsdottir, V. Steinthorsdottir, G. Sigurdsson, A.V. Thorsson, P.V. Carroll, M. Korbonits, R. Benediktsson, The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur. J. Endocrinol. / Eur. Fed. Endocr. Soc. 173(5), 655–664 (2015). https://​doi.​org/​10.​1530/​eje-15-0189 CrossRef
6.
Zurück zum Zitat E. Ferrante, M. Ferraroni, T. Castrignano, L. Menicatti, M. Anagni, G. Reimondo, P. Del Monte, D. Bernasconi, P. Loli, M. Faustini-Fustini, G. Borretta, M. Terzolo, M. Losa, A. Morabito, A. Spada, P. Beck-Peccoz, A.G. Lania, Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur. J. Endocrinol. / Eur. Fed. Endocr. Soc. 155(6), 823–829 (2006). https://doi.org/10.1530/eje.1.02298 CrossRef E. Ferrante, M. Ferraroni, T. Castrignano, L. Menicatti, M. Anagni, G. Reimondo, P. Del Monte, D. Bernasconi, P. Loli, M. Faustini-Fustini, G. Borretta, M. Terzolo, M. Losa, A. Morabito, A. Spada, P. Beck-Peccoz, A.G. Lania, Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur. J. Endocrinol. / Eur. Fed. Endocr. Soc. 155(6), 823–829 (2006). https://​doi.​org/​10.​1530/​eje.​1.​02298 CrossRef
14.
Zurück zum Zitat B. Tsuchiya, Y. Sato, T. Kameya, I. Okayasu, K. Mukai, Differential expression of N-cadherin and E-cadherin in normal human tissues. Arch. Histol. Cytol. 69(2), 135–145 (2006)CrossRef B. Tsuchiya, Y. Sato, T. Kameya, I. Okayasu, K. Mukai, Differential expression of N-cadherin and E-cadherin in normal human tissues. Arch. Histol. Cytol. 69(2), 135–145 (2006)CrossRef
16.
17.
Zurück zum Zitat M.S. Elston, A.J. Gill, J.V. Conaglen, A. Clarkson, R.J. Cook, N.S. Little, B.G. Robinson, R.J. Clifton-Bligh, K.L. McDonald, Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas. J. Clin. Endocrinol. Metab. 94(4), 1436–1442 (2009). https://doi.org/10.1210/jc.2008-2075 CrossRefPubMed M.S. Elston, A.J. Gill, J.V. Conaglen, A. Clarkson, R.J. Cook, N.S. Little, B.G. Robinson, R.J. Clifton-Bligh, K.L. McDonald, Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas. J. Clin. Endocrinol. Metab. 94(4), 1436–1442 (2009). https://​doi.​org/​10.​1210/​jc.​2008-2075 CrossRefPubMed
21.
Zurück zum Zitat O. Casar-Borota, A. Heck, S. Schulz, J.M. Nesland, J. Ramm-Pettersen, T. Lekva, I. Alafuzoff, J. Bollerslev, Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide. J. Clin. Endocrinol. Metab. 98(11), E1730–E1739 (2013). https://doi.org/10.1210/jc.2013-2145 CrossRefPubMed O. Casar-Borota, A. Heck, S. Schulz, J.M. Nesland, J. Ramm-Pettersen, T. Lekva, I. Alafuzoff, J. Bollerslev, Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide. J. Clin. Endocrinol. Metab. 98(11), E1730–E1739 (2013). https://​doi.​org/​10.​1210/​jc.​2013-2145 CrossRefPubMed
22.
Zurück zum Zitat W. Remmele, H.E. Stegner, [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Der Pathol. 8(3), 138–140 (1987) W. Remmele, H.E. Stegner, [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Der Pathol. 8(3), 138–140 (1987)
23.
Zurück zum Zitat M. Lee, A. Lupp, N. Mendoza, N. Martin, R. Beschorner, J. Honegger, J. Schlegel, T. Shively, E. Pulz, S. Schulz, F. Roncaroli, N.S. Pellegata, SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary. Endocr. Relat. Cancer 22(1), 111–119 (2015). https://doi.org/10.1530/erc-14-0472 CrossRefPubMed M. Lee, A. Lupp, N. Mendoza, N. Martin, R. Beschorner, J. Honegger, J. Schlegel, T. Shively, E. Pulz, S. Schulz, F. Roncaroli, N.S. Pellegata, SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary. Endocr. Relat. Cancer 22(1), 111–119 (2015). https://​doi.​org/​10.​1530/​erc-14-0472 CrossRefPubMed
24.
Zurück zum Zitat K.A. Oystese, O. Casar-Borota, K.R. Normann, M. Zucknick, J.P. Berg, J. Bollerslev, Estrogen receptor alpha, a sex-dependent predictor of aggressiveness in nonfunctioning pituitary adenomas: SSTR and sex hormone receptor distribution in NFPA. J. Clin. Endocrinol. Metab. 102(9), 3581–3590 (2017). https://doi.org/10.1210/jc.2017-00792 CrossRefPubMed K.A. Oystese, O. Casar-Borota, K.R. Normann, M. Zucknick, J.P. Berg, J. Bollerslev, Estrogen receptor alpha, a sex-dependent predictor of aggressiveness in nonfunctioning pituitary adenomas: SSTR and sex hormone receptor distribution in NFPA. J. Clin. Endocrinol. Metab. 102(9), 3581–3590 (2017). https://​doi.​org/​10.​1210/​jc.​2017-00792 CrossRefPubMed
26.
Zurück zum Zitat N. Chauvet, N. Romano, A.C. Meunier, E. Galibert, P. Fontanaud, M.N. Mathieu, G. Osterstock, P. Osterstock, E. Baccino, V. Rigau, H. Loiseau, S. Bouillot-Eimer, A. Barlier, P. Mollard, N. Coutry, Combining cadherin expression with molecular markers discriminates invasiveness in growth hormone and prolactin pituitary adenomas. J. Neuroendocrinol. 28(2), 12352 (2016). https://doi.org/10.1111/jne.12352 CrossRefPubMed N. Chauvet, N. Romano, A.C. Meunier, E. Galibert, P. Fontanaud, M.N. Mathieu, G. Osterstock, P. Osterstock, E. Baccino, V. Rigau, H. Loiseau, S. Bouillot-Eimer, A. Barlier, P. Mollard, N. Coutry, Combining cadherin expression with molecular markers discriminates invasiveness in growth hormone and prolactin pituitary adenomas. J. Neuroendocrinol. 28(2), 12352 (2016). https://​doi.​org/​10.​1111/​jne.​12352 CrossRefPubMed
30.
Zurück zum Zitat R.B. Hazan, G.R. Phillips, R.F. Qiao, L. Norton, S.A. Aaronson, Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J. Cell. Biol. 148(4), 779–790 (2000)CrossRef R.B. Hazan, G.R. Phillips, R.F. Qiao, L. Norton, S.A. Aaronson, Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J. Cell. Biol. 148(4), 779–790 (2000)CrossRef
31.
Zurück zum Zitat M.T. Nieman, R.S. Prudoff, K.R. Johnson, M.J. Wheelock, N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J. Cell. Biol. 147(3), 631–644 (1999)CrossRef M.T. Nieman, R.S. Prudoff, K.R. Johnson, M.J. Wheelock, N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J. Cell. Biol. 147(3), 631–644 (1999)CrossRef
33.
Zurück zum Zitat W. Jia, J. Zhu, T.A. Martin, A. Jiang, A.J. Sanders, W.G. Jiang, E.M.T. Epithelial-mesenchymal Transition, Markers in human pituitary adenomas indicate a clinical course. Anticancer Res. 35(5), 2635–2643 (2015)PubMed W. Jia, J. Zhu, T.A. Martin, A. Jiang, A.J. Sanders, W.G. Jiang, E.M.T. Epithelial-mesenchymal Transition, Markers in human pituitary adenomas indicate a clinical course. Anticancer Res. 35(5), 2635–2643 (2015)PubMed
34.
36.
Zurück zum Zitat K. Ito, I. Okamoto, N. Araki, Y. Kawano, M. Nakao, S. Fujiyama, K. Tomita, T. Mimori, H. Saya, Calcium influx triggers the sequential proteolysis of extracellular and cytoplasmic domains of E-cadherin, leading to loss of beta-catenin from cell-cell contacts. Oncogene 18(50), 7080–7090 (1999). https://doi.org/10.1038/sj.onc.1203191 CrossRefPubMed K. Ito, I. Okamoto, N. Araki, Y. Kawano, M. Nakao, S. Fujiyama, K. Tomita, T. Mimori, H. Saya, Calcium influx triggers the sequential proteolysis of extracellular and cytoplasmic domains of E-cadherin, leading to loss of beta-catenin from cell-cell contacts. Oncogene 18(50), 7080–7090 (1999). https://​doi.​org/​10.​1038/​sj.​onc.​1203191 CrossRefPubMed
38.
Zurück zum Zitat P. Bouris, S.S. Skandalis, Z. Piperigkou, N. Afratis, K. Karamanou, A.J. Aletras, A. Moustakas, A.D. Theocharis, N.K. Karamanos, Estrogen receptor alpha mediates epithelial to mesenchymal transition, expression of specific matrix effectors and functional properties of breast cancer cells. Matrix biology: journal of the International Society for. Matrix Biol. 43, 42–60 (2015). https://doi.org/10.1016/j.matbio.2015.02.008 CrossRefPubMed P. Bouris, S.S. Skandalis, Z. Piperigkou, N. Afratis, K. Karamanou, A.J. Aletras, A. Moustakas, A.D. Theocharis, N.K. Karamanos, Estrogen receptor alpha mediates epithelial to mesenchymal transition, expression of specific matrix effectors and functional properties of breast cancer cells. Matrix biology: journal of the International Society for. Matrix Biol. 43, 42–60 (2015). https://​doi.​org/​10.​1016/​j.​matbio.​2015.​02.​008 CrossRefPubMed
Metadaten
Titel
The role of E and N-cadherin in the postoperative course of gonadotroph pituitary tumours
Publikationsdatum
26.07.2018
Erschienen in
Endocrine / Ausgabe 2/2018
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-018-1679-0

Weitere Artikel der Ausgabe 2/2018

Endocrine 2/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.