Top

Published in:

01-07-2013 | Original Paper

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case–control study of 410 patients with 8 years post-operative follow-up

Authors: Jacqueline Trouillas, Pascal Roy, Nathalie Sturm, Emmanuelle Dantony, Christine Cortet-Rudelli, Gabriel Viennet, Jean-François Bonneville, Richard Assaker, Carole Auger, Thierry Brue, Aurélie Cornelius, Henry Dufour, Emmanuel Jouanneau, Patrick François, Françoise Galland, François Mougel, François Chapuis, Laurent Villeneuve, Claude-Alain Maurage, Dominique Figarella-Branger, Gérald Raverot, The members of HYPOPRONOS

Published in: Acta Neuropathologica | Issue 1/2013

Abstract

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.

Amar AP, Hinton DR, Krieger MD, Weiss MH (1999) Invasive pituitary adenomas: significance of proliferation parameters. Pituitary 2(2):117–122PubMedCrossRef

Asa SL (2011) Tumors of the Pituitary Gland AFIP Fascicle 15/4. 1st edn. p 275. ISBN: 9781933477152

Barker FG 2nd, Klibanski A, Swearingen B (2003) Transsphenoidal surgery for pituitary tumors in the United States, 1996–2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 88(10):4709–4719PubMedCrossRef

Breslow NE, Day NE (1980) Statistical methods in cancer research. In: The analysis of case-control studies, vol I, issue number 32. IARC Sci Publ, Lyon, pp 5–338

Cornelius A, Cortet-Rudelli C, Assaker R, Kerdraon O, Gevaert M-H, Prévot V, Lassalle P, Trouillas J, Delehedde M, Maurage C-A (2012) Endothelial expression of endocan is strongly associated with tumor progression in pituitary adenoma. Brain Pathol 22(6):757–764PubMedCrossRef

Cottier J-P, Destrieux C, Brunereau L, Bertrand P, Moreau L, Jan M, Herbreteau D (2000) Cavernous sinus invasion by pituitary adenoma: MR imaging. Radiology 215(2):463–469PubMed

Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A (2006) High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege. Belgium. J Clin Endocrinol Metab 91(12):4769–4775CrossRef

Delgrange E, Trouillas J, Maiter D, Donckier J, Tourniaire J (1997) Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. J Clin Endocrinol Metab 82(7):2102–2107PubMedCrossRef

Dubois S, Guyetant S, Menei P, Rodien P, Illouz F, Vielle B, Rohmer V (2007) Relevance of Ki-67 and prognostic factors for recurrence/progression of gonadotropic adenomas after first surgery. Eur J Endocrinol 157(2):141–147PubMedCrossRef

10.

Fernandez A, Karavitaki N, Wass JA (2010) Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 72(3):377–382CrossRef

11.

Figarella-Branger D, Trouillas J (2006) The new WHO classification of human pituitary tumors: comments. Acta Neuropathol 111(1):71–72PubMedCrossRef

12.

Francois P, Travers N, Lescanne E, Arbeille B, Jan M, Velut S (2010) The interperiosteo-dural concept applied to the perisellar compartment: a microanatomical and electron microscopic study. J Neurosurg 113(5):1045–1052PubMedCrossRef

13.

Fusco A, Zatelli MC, Bianchi A, Cimino V, Tilaro L, Veltri F, Angelini F, Lauriola L, Vellone V, Doglietto F, Ambrosio MR, Maira G, Giustina A, degli Uberti EC, Pontecorvi A, De Marinis L (2008) Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas. J Clin Endocrinol Metab 93(7):2746–2750PubMedCrossRef

14.

Galland F, Lacroix L, Saulnier P, Dessen P, Meduri G, Bernier M, Gaillard S, Guibourdenche J, Fournier T, Evain-Brion D, Bidart JM, Chanson P (2010) Differential gene expression profiles of invasive and non-invasive non-functioning pituitary adenomas based on microarray analysis. Endocr Relat Cancer 17(2):361–371PubMedCrossRef

15.

Gejman R, Swearingen B, Hedley-Whyte ET (2008) Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas. Hum Pathol 39(5):758–766PubMedCrossRef

16.

Grossman AB (2006) The 2004 World Health Organization classification of pituitary tumors: is it clinically helpful? Acta Neuropathol (Berl) 111(1):76–77CrossRef

17.

Heaney AP (2011) Clinical review: pituitary carcinoma: difficult diagnosis and treatment. J Clin Endocrinol Metab 96(12):3649–3660PubMedCrossRef

18.

Honegger J, Prettin C, Feuerhake F, Petrick M, Schulte-Monting J, Reincke M (2003) Expression of Ki-67 antigen in nonfunctioning pituitary adenomas: correlation with growth velocity and invasiveness. J Neurosurg 99(4):674–679PubMedCrossRef

19.

Horvath E, Kovacs K, Smyth HS, Cusimano M, Singer W (2005) Silent adenoma subtype 3 of the pituitary—immunohistochemical and ultrastructural classification: a review of 29 cases. Ultrastruct Pathol 29(6):511–524PubMedCrossRef

20.

Jaffrain-Rea ML, Di Stefano D, Minniti G, Esposito V, Bultrini A, Ferretti E, Santoro A, Faticanti Scucchi L, Gulino A, Cantore G (2002) A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. Endocr Relat Cancer 9(2):103–113PubMedCrossRef

21.

Kaltsas GA, Nomikos P, Kontogeorgos G, Buchfelder M, Grossman AB (2005) Clinical review: diagnosis and management of pituitary carcinomas. J Clin Endocrinol Metab 90(5):3089–3099PubMedCrossRef

22.

Knosp E, Kitz K, Perneczky A (1989) Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. Neurosurgery 25(6):927–930PubMedCrossRef

23.

Knosp E, Steiner E, Kitz K, Matula C (1993) Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33(4):610–617 (discussion 617–618)PubMedCrossRef

24.

Kovacs K, Horvath E, Ezrin C (1977) Pituitary adenomas. Pathol Annu 12(Pt 2):341–382PubMed

25.

Kovacs K, Scheithauer B, Horvath E, Lloyd RV (1996) The WHO classification of adenohypophysial neoplasms. A proposed five-tier scheme. Cancer 78:502–510PubMedCrossRef

26.

Laws ER Jr, Lopes MB (2006) The new WHO classification of pituitary tumors: highlights and areas of controversy. Acta Neuropathol 111(1):80–81PubMedCrossRef

27.

Lloyd RV, Kovacs K, Young Jr WF, Farrel WE, Asa SL, Trouillas J, Kontogeorgos G, Sano T, Scheithauer B, Horvath E (2004) Pituitary tumours : introduction. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) Tumours of the pituitary, chapter 1. Pathology and genetics of tumours of endocrine organs. World Hearth Organization Classification of Tumours. IARC Press, Lyon, pp 10–13

28.

Losa M, Mortini P, Barzaghi R, Ribotto P, Terreni MR, Marzoli SB, Pieralli S, Giovanelli M (2008) Early results of surgery in patients with nonfunctioning pituitary adenoma and analysis of the risk of tumor recurrence. J Neurosurg 108(3):525–532PubMedCrossRef

29.

Madsen H, Borges TM, Knox AJ, Michaelis KA, Xu M, Lillehei KO, Wierman ME, Kleinschmidt-DeMasters BK (2011) Giant pituitary adenomas: pathologic-radiographic correlations and lack of role for p53 and MIB-1 labeling. Am J Surg Pathol 35(8):1204–1213PubMedCrossRef

30.

McCormack AI, Wass JA, Grossman AB (2011) Aggressive pituitary tumours: the role of temozolomide and the assessment of MGMT status. Eur J Clin Invest 41(10):1133–1148PubMedCrossRef

31.

Meij BP, Lopes MB, Ellegala DB, Alden TD, Laws ER Jr (2002) The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery. J Neurosurg 96(2):195–208PubMedCrossRef

32.

Nose V, Ezzat S, Horvath E, Kovacs K, Laws ER, Lloyd R, Lopes MB, Asa SL (2011) Protocol for the examination of specimens from patients with primary pituitary tumors. Arch Pathol Lab Med 135(5):640–646PubMed

33.

Obari A, Sano T, Ohyama K, Kudo E, Qian ZR, Yoneda A, Rayhan N, Mustafizur Rahman M, Yamada S (2008) Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr Pathol 19(2):82–91PubMedCrossRef

34.

Pack SD, Qin LX, Pak E, Wang Y, Ault DO, Mannan P, Jaikumar S, Stratakis CA, Oldfield EH, Zhuang Z, Weil RJ (2005) Common genetic changes in hereditary and sporadic pituitary adenomas detected by comparative genomic hybridization. Genes Chromosomes Cancer 43(1):72–82PubMedCrossRef

35.

R Development Core Team (2009) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. http://www.R-project.org

36.

Ramirez C, Cheng S, Vargas G, Asa SL, Ezzat S, Gonzalez B, Cabrera L, Guinto G, Mercado M (2012) Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical study. J Clin Endocrinol Metab 97(5):1745–1751PubMedCrossRef

37.

Raverot G, Castinetti F, Jouanneau E, Morange I, Figarella-Branger D, Dufour H, Trouillas J, Brue T (2012) Pituitary carcinomas and aggressive pituitary tumours: merits and pitfalls of temozolomide treatment. Clin Endocrinol (Oxf) 76(6):769–775CrossRef

38.

Raverot G, Sturm N, de Fraipont F, Muller M, Salenave S, Caron P, Chabre O, Chanson P, Cortet-Rudelli C, Assaker R, Dufour H, Gaillard S, Francois P, Jouanneau E, Passagia JG, Bernier M, Cornelius A, Figarella-Branger D, Trouillas J, Borson-Chazot F, Brue T (2010) Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience. J Clin Endocrinol Metab 95(10):4592–4599PubMedCrossRef

39.

Raverot G, Wierinckx A, Dantony E, Auger C, Chapas G, Villeneuve L, Brue T, Figarella-Branger D, Roy P, Jouanneau E, Jan M, Lachuer J, Trouillas J (2010) Prognostic factors in prolactin pituitary tumors: clinical, histological, and molecular data from a series of 94 patients with a long postoperative follow-up. J Clin Endocrinol Metab 95(4):1708–1716PubMedCrossRef

40.

Raverot G, Wierinckx A, Jouanneau E, Auger C, Borson-Chazot F, Lachuer J, Pugeat M, Trouillas J (2010) Clinical, hormonal and molecular characterization of pituitary ACTH adenomas without (silent corticotroph adenomas) and with Cushing’s disease. Eur J Endocrinol 163(1):35–43PubMedCrossRef

41.

Rickert CH, Dockhorn-Dworniczak B, Busch G, Moskopp D, Albert FK, Rama B, Paulus W (2001) Increased chromosomal imbalances in recurrent pituitary adenomas. Acta Neuropathol 102(6):615–620PubMed

42.

Rickert CH, Scheithauer BW, Paulus W (2001) Chromosomal aberrations in pituitary carcinoma metastases. Acta Neuropathol 102(2):117–120PubMed

43.

Righi A, Agati P, Sisto A, Frank G, Faustini-Fustini M, Agati R, Mazzatenta D, Farnedi A, Menetti F, Marucci G, Foschini MP (2012) A classification tree approach for pituitary adenomas. Hum Pathol 43(10):1627–1637PubMedCrossRef

44.

Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Korner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449(4):395–401PubMedCrossRef

45.

Roelfsema F, Biermasz NR, Pereira AM (2012) Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. Pituitary 15(1):71–83PubMedCrossRef

46.

Saeger W, Ludecke B, Ludecke DK (2008) Clinical tumor growth and comparison with proliferation markers in non-functioning (inactive) pituitary adenomas. Exp Clin Endocrinol Diabetes 116(2):80–85PubMedCrossRef

47.

Saeger W, Ludecke DK, Buchfelder M, Fahlbusch R, Quabbe HJ, Petersenn S (2007) Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol 156(2):203–216PubMedCrossRef

48.

Salehi F, Agur A, Scheithauer BW, Kovacs K, Lloyd RV, Cusimano M (2009) Ki-67 in pituitary neoplasms: a review—part I. Neurosurgery 65(3):429–437 (discussion 437)PubMedCrossRef

49.

Scheithauer BW, Kovacs KT, Laws ER Jr, Randall RV (1986) Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65(6):733–744PubMedCrossRef

50.

Scheithauer BW, Kurtkaya-Yapicier O, Kovacs KT, Young WF Jr, Lloyd RV (2005) Pituitary carcinoma: a clinicopathological review. Neurosurgery 56(5):1066–1074PubMed

51.

Solcia E, Klöppel G, Sobin L (2000) Histological classification of adenohypophyseal tumours. Histological classification of endocrine tumours. Springer, BerlinCrossRef

52.

Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws ER Jr (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38(1):99–106PubMedCrossRef

53.

Thapar K, Scheithauer BW, Kovacs K, Pernicone PJ, Laws ER Jr (1996) p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 38(4):765–770PubMedCrossRef

54.

Trouillas J, Cure M, Lheritier M, Guichard Y, Girod C (1974) Essai de classification cytofonctionnelle de 19 adénomes hypophysaires d’après des données histologiques, immunocytochimiques, biométriques et ultrastructurales. Rev Oto-Neuro-Ophtalmol 47(3):223–236

55.

Trouillas J, Daniel L, Guigard MP, Tong S, Gouvernet J, Jouanneau E, Jan M, Perrin G, Fischer G, Tabarin A, Rougon G, Figarella-Branger D (2003) Polysialylated neural cell adhesion molecules expressed in human pituitary tumors and related to extrasellar invasion. J Neurosurg 98(5):1084–1093PubMedCrossRef

56.

Trouillas J, Girod C (1996) Pathology of pituitary adenomas. In: Landolt AM, Vance ML, Reilly PL (eds) Pituitary adenomas. Churchill Livingstone, New York, pp 27–46

57.

Trouillas J, Labat-Moleur F, Sturm N, Kujas M, Heymann MF, Figarella-Branger D, Patey M, Mazucca M, Decullier E, Verges B, Chabre O, Calender A (2008) Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol 32(4):534–543PubMedCrossRef

58.

Wierinckx A, Auger C, Devauchelle P, Reynaud A, Chevallier P, Jan M, Perrin G, Fevre-Montange M, Rey C, Figarella-Branger D, Raverot G, Belin MF, Lachuer J, Trouillas J (2007) A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors. Endocr Relat Cancer 14(3):887–900PubMedCrossRef

59.

Wierinckx A, Raverot G, Nazaret N, Jouanneau E, Auger C, Lachuer J, Trouillas J (2010) Proliferation markers of human pituitary tumors: contribution of a genome-wide transcriptome approach. Mol Cell Endocrinol 326(1–2):30–39PubMedCrossRef

60.

Wierinckx A, Roche M, Raverot G, Legras-Lachuer C, Croze S, Nazaret N, Rey C, Auger C, Jouanneau E, Chanson P, Trouillas J, Lachuer J (2011) Integrated genomic profiling identifies loss of chromosome 11p impacting transcriptomic activity in aggressive pituitary PRL tumors. Brain Pathol 21(5):533–543PubMed

61.

Wolfsberger S, Knosp E (2006) Comments on the WHO 2004 classification of pituitary tumors. Acta Neuropathol 111(1):66–67PubMedCrossRef

62.

Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr (2011) Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 114(2):336–344PubMedCrossRef

63.

Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (1999) Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 84(2):761–767PubMedCrossRef

Title: A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case–control study of 410 patients with 8 years post-operative follow-up
Authors: Jacqueline Trouillas
Pascal Roy
Nathalie Sturm
Emmanuelle Dantony
Christine Cortet-Rudelli
Gabriel Viennet
Jean-François Bonneville
Richard Assaker
Carole Auger
Thierry Brue
Aurélie Cornelius
Henry Dufour
Emmanuel Jouanneau
Patrick François
Françoise Galland
François Mougel
François Chapuis
Laurent Villeneuve
Claude-Alain Maurage
Dominique Figarella-Branger
Gérald Raverot
The members of HYPOPRONOS
Publication date: 01-07-2013
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 1/2013
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-013-1084-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case–control study of 410 patients with 8 years post-operative follow-up

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2013

Charcot–Marie–Tooth causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments

Mild traumatic brain injury in the mouse induces axotomy primarily within the axon initial segment

Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy

TDP-43 deposition in prospectively followed, cognitively normal elderly individuals: correlation with argyrophilic grains but not other concomitant pathologies

Transcriptome analysis of MENX-associated rat pituitary adenomas identifies novel molecular mechanisms involved in the pathogenesis of human pituitary gonadotroph adenomas

Robust cytoplasmic accumulation of phosphorylated TDP-43 in transgenic models of tauopathy