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Horm Metab Res 2018; 50(07): 575-581
DOI: 10.1055/a-0593-5956
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Impact of the Canonical Wnt Pathway Activation on the Pathogenesis and Prognosis of Adamantinomatous Craniopharyngiomas

Carlos Eduardo Barros Jucá   *
1   Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Leandro Machado Colli   *
2   Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Clarissa Silva Martins
2   Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Marina Lanciotti Campanini
2   Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Beatriz Paixão
2   Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Renata Viana Jucá
3   Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Fabiano Pinto Saggioro
3   Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Ricardo Santos de Oliveira
1   Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Ayrton Custódio Moreira
2   Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Hélio Rubens Machado
1   Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Luciano Neder
3   Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Sonir Rauber Antonini
4   Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
,
Margaret de Castro
2   Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
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Publikationsverlauf

received 20. August 2017

accepted 07. März 2018

Publikationsdatum:
06. April 2018 (online)

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Abstract

CTNNB1 mutations and abnormal β-catenin distribution are associated with the pathogenesis of adamantinomatous craniopharyngioma (aCP). We evaluated the expression of the canonical Wnt pathway components in aCPs and its association with CTNNB1 mutations and tumor progression. Tumor samples from 14 aCP patients and normal anterior pituitary samples from eight individuals without pituitary disease were studied. Gene expression of Wnt pathway activator (WNT4), inhibitors (SFRP1, DKK3, AXIN1, and APC), transcriptional activator (TCF7), target genes (MYC, WISP2, and, CDH1), and Wnt modulator (TP53) was evaluated by qPCR. β-Catenin, MYC, and WISP2 expression was determined by immunohistochemistry (IHC). The transcription levels of all genes studied, except APC, were higher in aCPs as compared to controls and TCF7 mRNA levels correlated with CTNNB1 mutation. CDH1 mRNA was overexpressed in tumor samples of patients with disease progression in comparison to those with stable disease. β-Catenin was positive and aberrantly distributed in 11 out of 14 tumor samples. Stronger β-catenin immunostaining associated positively with tumor progression. MYC positive staining was found in 10 out of 14 cases, whereas all aCPs were negative for WISP2. Wnt pathway genes were overexpressed in aCPs harboring CTNNB1 mutations and in patients with progressive disease. Recurrence was associated with stronger staining for β-catenin. These data suggest that Wnt pathway activation contributes to the pathogenesis and prognosis of aCPs.

Key words

craniopharyngioma - Wnt pathway - β-catenin - prognosis - recurrence

* These authors contributed equally to the work


 

  • References

  • 1 Mortini P, Losa M, Pozzobon G, Barzaghi R, Riva M, Acerno S, Angius D, Weber G, Chiumello G, Giovanelli M. Neurosurgical treatment of craniopharyngioma in adults and children: Early and long-term results in a large case series. J Neurosurg 2011; 114: 1350-1359
    CrossrefPubMedGoogle Scholar
  • 2 Garnett MR, Puget S, Grill J, Sainte-Rose C. Craniopharyngioma. Orphanet J Rare Dis 2007; 2: 18
    CrossrefPubMedGoogle Scholar
  • 3 Kaltsas GA, Evanson J, Chrisoulidou A, Grossman AB. The diagnosis and management of parasellar tumours of the pituitary. Endocr Relat Cancer 2008; 15: 885-903
    CrossrefPubMedGoogle Scholar
  • 4 Karavitaki N, Cudlip S, Adams CB, Wass JA. Craniopharyngiomas. Endocr Rev 2006; 27: 371-397
    CrossrefPubMedGoogle Scholar
  • 5 Nogueira MC, Berbel Júnior AS, Koenigkam-Santos M, Moreira AC, Nonino CB, de Castro M. Nutritional and endocrinologic evaluation of patients with craniopharyngioma. Clinical Nutrition ESPEN 2015; 10: e213-e218
    CrossrefPubMedGoogle Scholar
  • 6 Muller HL, Merchant TE, Puget S, Martinez-Barbera JP. New outlook on the diagnosis, treatment and follow-up of childhood-onset craniopharyngioma. Nat Rev Endocrinol 2017; 13: 299-312
    CrossrefPubMedGoogle Scholar
  • 7 Goldberg GM, Eshbaugh DE. Squamous cell nests of the pituitary gland as related to the origin of craniopharyngiomas. A study of their presence in the newborn and infants up to age four. Arch Pathol 1960; 70: 293-299
    PubMedGoogle Scholar
  • 8 Asa SL, Kovacs K, Bilbao JM. The pars tuberalis of the human pituitary. A histologic, immunohistochemical, ultrastructural and immunoelectron microscopic analysis. Virchows Arch A Pathol Anat Histopathol 1983; 399: 49-59
    PubMedGoogle Scholar
  • 9 Pettorini BL, Frassanito P, Caldarelli M, Tamburrini G, Massimi L, Di Rocco C. Molecular pathogenesis of craniopharyngioma: Switching from a surgical approach to a biological one. Neurosurg Focus 2010; 28: E1
    CrossrefPubMedGoogle Scholar
  • 10 Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, Thorner AR, Lawrence MS, Rodriguez FJ, Bernardo LA, Schubert L, Sunkavalli A, Shillingford N, Calicchio ML, Lidov HG, Taha H, Martinez-Lage M, Santi M, Storm PB, Lee JY, Palmer JN, Adappa ND, Scott RM, Dunn IF, Laws Jr. ER, Stewart C, Ligon KL, Hoang MP, Van Hummelen P, Hahn WC, Louis DN, Resnick AC, Kieran MW, Getz G, Santagata S. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet 2014; 46: 161-165
    CrossrefPubMedGoogle Scholar
  • 11 Hassanein AM, Glanz SM, Kessler HP, Eskin TA, Liu C. beta-Catenin is expressed aberrantly in tumors expressing shadow cells. Pilomatricoma, craniopharyngioma, and calcifying odontogenic cyst. Am J Clin Pathol 2003; 120: 732-736
    CrossrefPubMedGoogle Scholar
  • 12 Kato K, Nakatani Y, Kanno H, Inayama Y, Ijiri R, Nagahara N, Miyake T, Tanaka M, Ito Y, Aida N, Tachibana K, Sekido K, Tanaka Y. Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma. J Pathol 2004; 203: 814-821
    CrossrefPubMedGoogle Scholar
  • 13 Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, Sakamoto M, Hirohashi S. Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol 2002; 161: 1997-2001
    CrossrefPubMedGoogle Scholar
  • 14 Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrubl F, Hahnen E, Kreutzer J, Fahlbusch R. Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol 2005; 109: 589-597
    CrossrefPubMedGoogle Scholar
  • 15 Goschzik T, Gessi M, Dreschmann V, Gebhardt U, Wang L, Yamaguchi S, Wheeler DA, Lauriola L, Lau CC, Muller HL, Pietsch T. Genomic alterations of adamantinomatous and papillary craniopharyngioma. J Neuropathol Exp Neurol 2017; 76: 126-134
    PubMedGoogle Scholar
  • 16 van Amerongen R, Mikels A, Nusse R. Alternative wnt signaling is initiated by distinct receptors. Sci Signal 2008; 1: re9
    PubMedGoogle Scholar
  • 17 Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze'ev A. Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev 2002; 16: 2058-2072
    CrossrefPubMedGoogle Scholar
  • 18 Pai SG, Carneiro BA, Mota JM, Costa R, Leite CA, Barroso-Sousa R, Kaplan JB, Chae YK, Giles FJ. Wnt/beta-catenin pathway: modulating anticancer immune response. J Hematol Oncol 2017; 10: 101
    CrossrefPubMedGoogle Scholar
  • 19 Campanini ML, Colli LM, Paixao BM, Cabral TP, Amaral FC, Machado HR, Neder LS, Saggioro F, Moreira AC, Antonini SR, de Castro M. CTNNB1 gene mutations, pituitary transcription factors, and MicroRNA expression involvement in the pathogenesis of adamantinomatous craniopharyngiomas. Horm Cancer 2010; 1: 187-196
    CrossrefPubMedGoogle Scholar
  • 20 Gomes DC, Jamra SA, Leal LF, Colli LM, Campanini ML, Oliveira RS, Martinelli Jr. CE, Elias PC, Moreira AC, Machado HR, Saggioro F, Neder L, Castro M, Antonini SR. Sonic Hedgehog pathway is upregulated in adamantinomatous craniopharyngiomas. Eur J Endocrinol 2015; 172: 603-608
    CrossrefPubMedGoogle Scholar
  • 21 Gaston-Massuet C, Andoniadou CL, Signore M, Jayakody SA, Charolidi N, Kyeyune R, Vernay B, Jacques TS, Taketo MM, Le Tissier P, Dattani MT, Martinez-Barbera JP. Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans. Proc Natl Acad Sci U S A 2011; 108: 11482-11487
    CrossrefPubMedGoogle Scholar
  • 22 Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: e45
    CrossrefPubMedGoogle Scholar
  • 23 Colli LM, Saggioro F, Serafini LN, Camargo RC, Machado HR, Moreira AC, Antonini SR, de Castro M. Components of the canonical and non-canonical Wnt pathways are not mis-expressed in pituitary tumors. PLoS One 2013; 8: e62424
    CrossrefPubMedGoogle Scholar
  • 24 Gump JM, Donson AM, Birks DK, Amani VM, Rao KK, Griesinger AM, Kleinschmidt-DeMasters BK, Johnston JM, Anderson RC, Rosenfeld A, Handler M, Gore L, Foreman N, Hankinson TC. Identification of targets for rational pharmacological therapy in childhood craniopharyngioma. Acta Neuropathol Commun 2015; 3: 30
    CrossrefPubMedGoogle Scholar
  • 25 Holsken A, Sill M, Merkle J, Schweizer L, Buchfelder M, Flitsch J, Fahlbusch R, Metzler M, Kool M, Pfister SM, von Deimling A, Capper D, Jones DT, Buslei R. Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles. Acta Neuropathol Commun 2016; 4: 20
    CrossrefPubMedGoogle Scholar
  • 26 Elston MS, Clifton-Bligh RJ. Identification of Wnt family inhibitors: a pituitary tumor directed whole genome approach. Mol Cell Endocrinol 2010; 326: 48-54
    CrossrefPubMedGoogle Scholar
  • 27 Holsken A, Kreutzer J, Hofmann BM, Hans V, Oppel F, Buchfelder M, Fahlbusch R, Blumcke I, Buslei R. Target gene activation of the Wnt signaling pathway in nuclear beta-catenin accumulating cells of adamantinomatous craniopharyngiomas. Brain Pathol 2009; 19: 357-364
    CrossrefPubMedGoogle Scholar
  • 28 Preda V, Larkin SJ, Karavitaki N, Ansorge O, Grossman AB. The Wnt signalling cascade and the adherens junction complex in craniopharyngioma tumorigenesis. Endocr Pathol 2015; 26: 1-8
    CrossrefPubMedGoogle Scholar
  • 29 Qi ST, Zhou J, Pan J, Zhang C, Silky C, Yan XR. Epithelial-mesenchymal transition and clinicopathological correlation in craniopharyngioma. Histopathology 2012; 61: 711-725
    CrossrefPubMedGoogle Scholar
  • 30 Buslei R, Holsken A, Hofmann B, Kreutzer J, Siebzehnrubl F, Hans V, Oppel F, Buchfelder M, Fahlbusch R, Blumcke I. Nuclear beta-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas. Acta Neuropathol 2007; 113: 585-590
    CrossrefPubMedGoogle Scholar
  • 31 Samis J, Vanin EF, Sredni ST, de Bonaldo Mde F, Costa FF, Tomita T, Habiby R, Zimmerman D, Soares MB. Extensive miRNA expression analysis in craniopharyngiomas. Childs Nerv Syst 2016; 32: 1617-1624
    CrossrefPubMedGoogle Scholar
  • 32 Davies SR, Davies ML, Sanders A, Parr C, Torkington J, Jiang WG. Differential expression of the CCN family member WISP-1, WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications. Int J Oncol 2010; 36: 1129-1136
    PubMedGoogle Scholar
  • 33 Leal LF, Mermejo LM, Ramalho LZ, Martinelli Jr. CE, Yunes JA, Seidinger AL, Mastellaro MJ, Cardinalli IA, Brandalise SR, Moreira AC, Tone LG, Scrideli CA, Castro M, Antonini SR. Wnt/beta-catenin pathway deregulation in childhood adrenocortical tumors. J Clin Endocrinol Metab 2011; 96: 3106-3114
    CrossrefPubMedGoogle Scholar
  • 34 Szabo PM, Racz K, Igaz P. Underexpression of C-myc in adrenocortical cancer: A major pathogenic event?. Horm Metab Res 2011; 43: 297-299
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 35 Zoicas F, Schofl C. Craniopharyngioma in adults. Front Endocrinol (Lausanne) 2012; 3: 46
    PubMedGoogle Scholar
  • 36 Li Z, Xu J, Huang S, You C. Aberrant membranous expression of beta-catenin predicts poor prognosis in patients with craniopharyngioma. Ann Diagn Pathol 2015; 19: 403-408
    CrossrefPubMedGoogle Scholar
  • 37 Holsken A, Buchfelder M, Fahlbusch R, Blumcke I, Buslei R. Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling. Acta Neuropathol 2010; 119: 631-639
    CrossrefPubMedGoogle Scholar