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Published in: Journal of Experimental & Clinical Cancer Research 1/2017

Open Access 01-12-2017 | Research

Can recurrences be predicted in craniopharyngiomas? β-catenin coexisting with stem cells markers and p-ATM in a clinicopathologic study of 45cases

Authors: Elia Guadagno, Oreste de Divitiis, Domenico Solari, Giorgio Borrelli, Umberto Marcello Bracale, Alberto Di Somma, Paolo Cappabianca, Marialaura Del Basso De Caro

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

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Abstract

Background

Recurrence is a common feature of craniopharyngiomas, benign tumors that origin from squamous epithelial remnants of Rathke’s pouch- arising at any segment of its whole course. There are two histotypes, showing different morphology and clinical behavior: adamantinomatous(adaCP) and papillary (papCP). An univocal strategy of management has not yet been defined, being considered the combination of surgery and radiotherapy the most effective, especially in case of incomplete resection. Therefore, the identification of factors influencing the biological and clinical behaviour is of paramount importance.
β-catenin is a cell-cell adhesion protein, whose nuclear localization has been linked to the pathogenesis of adaCP: its nuclear accumulation is associated to the presence of a tumor stem cell subpopulation. The latter is made of cells capable of self-renewal, hence believed to be responsible of recurrence, metastases and resistance to therapy in all tumors.
ATM is a kinase activated by autophosphorylation (p-ATM) upon DNA double-strand breaks. It is involved not only in DNA repair, but also in tumor migration and invasiveness. Its expression may have prognostic implications in many neoplastic diseases.

Methods

In this study, we measured the immunohistochemical expression of β-catenin, stem cell markers (CD133, CD166), Ki67 and pATMin 45 craniopharyngiomas and correlated it with clinicopathologic features.

Results

Statistical analysis revealed strong correlation of β-catenin with recurrence (p = 0.0039), Ki67 (p = 0.0011, r = 0.4903) and CD166 (p = 0.0002, r = 0.6218). A slight tendency to a higher expression of β-catenin was recorded for adaCP rather than papCP (p = 0.0895).Fisher’s exact test showed that CD166 was significantlyrelated with recurrence (p = 0.0040). Furthermore, cytoplasmic pATM was more expressed in adaCPs (p = 0.0470), compared to papCPs that displayed a more evident nuclear signal (p = 0.0313) instead.

Conclusions

Backing upon these data, we could weigh in on the need of identifying β-catenin and CD166 as prognostic markersthat could be useful in predicting thebiologicalbehavior, as recurrence risk incraniopharyngiomas. The final goal is to drew up a prognostic algorithm to be of aid in the planning of an appropriate treatment strategy. Furthermore, our findings demonstrate that pATM could be used as additional distinction-marker between the two histotypes.
Literature
1.
go back to reference Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO classification of tumours of the central nervous system. Lyon: Int Agency Res. 4th Edition revised, 2016. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO classification of tumours of the central nervous system. Lyon: Int Agency Res. 4th Edition revised, 2016.
2.
go back to reference Clark AJ, Cage TA, Aranda D, Parsa AT, Sun PP, Auguste KI, et al. A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma. Childs Nerv Syst. 2013;29:231–8.CrossRefPubMed Clark AJ, Cage TA, Aranda D, Parsa AT, Sun PP, Auguste KI, et al. A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma. Childs Nerv Syst. 2013;29:231–8.CrossRefPubMed
3.
go back to reference Sartoretti-Schefer S, WichmannW AA, Valavanis A. MR differentiation of adamantinomatous and squamous-papillary craniopharyngiomas. AJNR Am J Neuroradiol. 1997;18:77–87. Sartoretti-Schefer S, WichmannW AA, Valavanis A. MR differentiation of adamantinomatous and squamous-papillary craniopharyngiomas. AJNR Am J Neuroradiol. 1997;18:77–87.
4.
go back to reference Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, et al. Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol. 2002;161:1997–2001.CrossRefPubMedPubMedCentral Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, et al. Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol. 2002;161:1997–2001.CrossRefPubMedPubMedCentral
5.
go back to reference Hölsken A, Kreutzer J, Hofmann BM, Hans V, Oppel F, Buchfelder M, et al. Target gene activation of the Wnt signaling pathway in nuclear beta-catenin accumulating cells of adamantinomatous craniopharyngiomas. Brain Pathol. 2009;19:357–64.CrossRefPubMed Hölsken A, Kreutzer J, Hofmann BM, Hans V, Oppel F, Buchfelder M, et al. Target gene activation of the Wnt signaling pathway in nuclear beta-catenin accumulating cells of adamantinomatous craniopharyngiomas. Brain Pathol. 2009;19:357–64.CrossRefPubMed
6.
go back to reference Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrübl F, et al. Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol. 2005;109:589–97.CrossRefPubMed Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrübl F, et al. Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol. 2005;109:589–97.CrossRefPubMed
7.
go back to reference Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, Thorner AR, et al. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet. 2014;46:161–5.CrossRefPubMedPubMedCentral Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, Thorner AR, et al. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet. 2014;46:161–5.CrossRefPubMedPubMedCentral
8.
go back to reference Brastianos PK, Santagata S. ENDOCRINE TUMORS: BRAF V600E mutations in papillary craniopharyngioma. Eur J Endocrinol. 2016;174:R139–44.CrossRefPubMed Brastianos PK, Santagata S. ENDOCRINE TUMORS: BRAF V600E mutations in papillary craniopharyngioma. Eur J Endocrinol. 2016;174:R139–44.CrossRefPubMed
9.
go back to reference Harada N, Tamai Y, Ishikawa T, Sauer B, Takaku K, Oshima M, et al. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J. 1999;18:5931–42.CrossRefPubMedPubMedCentral Harada N, Tamai Y, Ishikawa T, Sauer B, Takaku K, Oshima M, et al. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J. 1999;18:5931–42.CrossRefPubMedPubMedCentral
10.
11.
go back to reference Hölsken A, Stache C, Schlaffer SM, Flitsch J, Fahlbusch R, Buchfelder M, et al. Adamantinomatous craniopharyngiomas express tumor stem cell makers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche? Pituitary. 2014;17:546–56. Hölsken A, Stache C, Schlaffer SM, Flitsch J, Fahlbusch R, Buchfelder M, et al. Adamantinomatous craniopharyngiomas express tumor stem cell makers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche? Pituitary. 2014;17:546–56.
12.
go back to reference Yaşargil MG, Curcic M, Kis M, Siegenthaler G, Teddy PJ, Roth P. Total removal of craniopharyngiomas. Approaches and long-term results in 144 patients. J Neurosurg. 1990;73:3–11.CrossRefPubMed Yaşargil MG, Curcic M, Kis M, Siegenthaler G, Teddy PJ, Roth P. Total removal of craniopharyngiomas. Approaches and long-term results in 144 patients. J Neurosurg. 1990;73:3–11.CrossRefPubMed
13.
go back to reference Cavallo LM, Prevedello DM, Solari D, Gardner PA, Esposito F, Snyderman CH, et al. Extended endoscopic endonasal transsphenoidal approach for residual or recurrent craniopharyngiomas. J Neurosurg. 2009;111:578–89.CrossRefPubMed Cavallo LM, Prevedello DM, Solari D, Gardner PA, Esposito F, Snyderman CH, et al. Extended endoscopic endonasal transsphenoidal approach for residual or recurrent craniopharyngiomas. J Neurosurg. 2009;111:578–89.CrossRefPubMed
14.
go back to reference Cavallo LM, Frank G, Cappabianca P, Solari D, Mazzatenta D, Villa A, et al. The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients. J Neurosurg. 2014;121:100–13.CrossRefPubMed Cavallo LM, Frank G, Cappabianca P, Solari D, Mazzatenta D, Villa A, et al. The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients. J Neurosurg. 2014;121:100–13.CrossRefPubMed
15.
go back to reference Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, et al. Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome. Neurosurgery. 1994;35:1001–10.CrossRefPubMed Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, et al. Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome. Neurosurgery. 1994;35:1001–10.CrossRefPubMed
16.
go back to reference Samii M, Samii A. Surgical management of craniopharyngiomas. In: Schmidek HH, ed. Schmidek & Sweet Operative neurosurgical techniques. Indications, methods and results. Philadelphia: W. B. Saunders; 2000;1:489-502. Samii M, Samii A. Surgical management of craniopharyngiomas. In: Schmidek HH, ed. Schmidek & Sweet Operative neurosurgical techniques. Indications, methods and results. Philadelphia: W. B. Saunders; 2000;1:489-502.
17.
go back to reference Prieto R, Pascual JM, Subhi-Issa I, Jorquera M, Yus M, Martínez R. Predictive factors for craniopharyngioma recurrence: a systematic review and illustrative case report of a rapid recurrence. World Neurosurg. 2013;79:733–49. Prieto R, Pascual JM, Subhi-Issa I, Jorquera M, Yus M, Martínez R. Predictive factors for craniopharyngioma recurrence: a systematic review and illustrative case report of a rapid recurrence. World Neurosurg. 2013;79:733–49.
18.
go back to reference Wu B, Sun C, Feng F, Ge M, Xia L. Do relevant markers of cancer stem cells CD133 and Nestin indicate a poor prognosis in glioma patients? A systematic review and meta-analysis. J Exp Clin Cancer Res. 2015;34:44. Wu B, Sun C, Feng F, Ge M, Xia L. Do relevant markers of cancer stem cells CD133 and Nestin indicate a poor prognosis in glioma patients? A systematic review and meta-analysis. J Exp Clin Cancer Res. 2015;34:44.
19.
go back to reference Kaur S, Singh G, Kaur K. Cancer stem cells: an insight and future perspective. J Cancer Res Ther. 2014;10:846–52.CrossRefPubMed Kaur S, Singh G, Kaur K. Cancer stem cells: an insight and future perspective. J Cancer Res Ther. 2014;10:846–52.CrossRefPubMed
20.
go back to reference Zhang W, Chen H, Lv S, Yang H. High CD133 expression is associated with worse prognosis in patients with Glioblastoma. Mol Neurobiol. 2016;53:2354–60. Zhang W, Chen H, Lv S, Yang H. High CD133 expression is associated with worse prognosis in patients with Glioblastoma. Mol Neurobiol. 2016;53:2354–60.
21.
go back to reference Guadagno E, Borrelli G, Califano M, Calì G, Solari D, Del Basso De Caro M. Immunohistochemical expression of stem cell markers CD44 and nestin in glioblastomas: evaluation of their prognostic significance. Pathol Res Pract. 2016;212:825–32. Guadagno E, Borrelli G, Califano M, Calì G, Solari D, Del Basso De Caro M. Immunohistochemical expression of stem cell markers CD44 and nestin in glioblastomas: evaluation of their prognostic significance. Pathol Res Pract. 2016;212:825–32.
22.
go back to reference Eom DW, Hong SM, Kim G, Bae YK, Jang KT, Yu E. Prognostic significance of CD44v6, CD133, CD166, and ALDH1 expression in small intestinal adenocarcinoma. Appl Immunohistochem Mol Morphol. 2015;23:682–8.CrossRefPubMed Eom DW, Hong SM, Kim G, Bae YK, Jang KT, Yu E. Prognostic significance of CD44v6, CD133, CD166, and ALDH1 expression in small intestinal adenocarcinoma. Appl Immunohistochem Mol Morphol. 2015;23:682–8.CrossRefPubMed
23.
go back to reference Lee JH, Paull TT. Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene. 2007;26:7741–8.CrossRefPubMed Lee JH, Paull TT. Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene. 2007;26:7741–8.CrossRefPubMed
24.
go back to reference Novak A, Dedhar S. Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci. 1999;56:523–37.CrossRefPubMed Novak A, Dedhar S. Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci. 1999;56:523–37.CrossRefPubMed
26.
go back to reference van Kempen LC, van den Oord JJ, van Muijen GN, Weidle UH, Bloemers HP, Swart GW. Activated leukocyte cell adhesion molecule/CD166, a marker of tumor progression in primary malignant melanoma of the skin. Am J Pathol. 2000;156:769–74.CrossRefPubMedPubMedCentral van Kempen LC, van den Oord JJ, van Muijen GN, Weidle UH, Bloemers HP, Swart GW. Activated leukocyte cell adhesion molecule/CD166, a marker of tumor progression in primary malignant melanoma of the skin. Am J Pathol. 2000;156:769–74.CrossRefPubMedPubMedCentral
27.
go back to reference Ofori-Acquah SF, King JA. Activated leukocyte cell adhesion molecule: a new paradox in cancer. Transl Res. 2008;151:122–8.CrossRefPubMed Ofori-Acquah SF, King JA. Activated leukocyte cell adhesion molecule: a new paradox in cancer. Transl Res. 2008;151:122–8.CrossRefPubMed
28.
go back to reference Verma A, Shukla NK, Deo SV, Gupta SD, Ralhan R. MEMD/ALCAM: a potential marker for tumor invasion and nodal metastasis in esophageal squamous cell carcinoma. Oncology. 2005;68:462–70. Verma A, Shukla NK, Deo SV, Gupta SD, Ralhan R. MEMD/ALCAM: a potential marker for tumor invasion and nodal metastasis in esophageal squamous cell carcinoma. Oncology. 2005;68:462–70.
29.
go back to reference King JA, Ofori-Acquah SF, Stevens T, Al-Mehdi AB, Fodstad O, Jiang WG. Activated leukocyte cell adhesion molecule in breast cancer: prognostic indicator. Breast Cancer Res. 2004;6:R478–87.CrossRefPubMedPubMedCentral King JA, Ofori-Acquah SF, Stevens T, Al-Mehdi AB, Fodstad O, Jiang WG. Activated leukocyte cell adhesion molecule in breast cancer: prognostic indicator. Breast Cancer Res. 2004;6:R478–87.CrossRefPubMedPubMedCentral
30.
go back to reference Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104:10158–63.CrossRefPubMedPubMedCentral Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104:10158–63.CrossRefPubMedPubMedCentral
31.
go back to reference Rajasekhar VK, Studer L, Gerald W, Socci ND, Scher HI. Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-kappa B signalling. Nat Commun. 2011;2:162.CrossRefPubMedPubMedCentral Rajasekhar VK, Studer L, Gerald W, Socci ND, Scher HI. Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-kappa B signalling. Nat Commun. 2011;2:162.CrossRefPubMedPubMedCentral
32.
go back to reference Chang CV, Araujo RV, Cirqueira CS, Cani CM, Matushita H, Cescato VA, et al. Differential expression of stem cell markers in human Adamantinomatous Craniopharyngioma and pituitary adenoma. Neuroendocrinology. 2017;104:183–93. Chang CV, Araujo RV, Cirqueira CS, Cani CM, Matushita H, Cescato VA, et al. Differential expression of stem cell markers in human Adamantinomatous Craniopharyngioma and pituitary adenoma. Neuroendocrinology. 2017;104:183–93.
33.
go back to reference Alexander A, Cai SL, Kim J, Nanez A, Sahin M, KH ML, et al. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci U S A. 2010;107:4153–8. Alexander A, Cai SL, Kim J, Nanez A, Sahin M, KH ML, et al. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci U S A. 2010;107:4153–8.
34.
go back to reference Yan Y, Xu Z, Dai S, Qian L, Sun L, Gong Z. Targeting autophagy to sensitive glioma to temozolomide treatment. J ExpClin Cancer Res. 2016;35:23. Yan Y, Xu Z, Dai S, Qian L, Sun L, Gong Z. Targeting autophagy to sensitive glioma to temozolomide treatment. J ExpClin Cancer Res. 2016;35:23.
Metadata
Title
Can recurrences be predicted in craniopharyngiomas? β-catenin coexisting with stem cells markers and p-ATM in a clinicopathologic study of 45cases
Authors
Elia Guadagno
Oreste de Divitiis
Domenico Solari
Giorgio Borrelli
Umberto Marcello Bracale
Alberto Di Somma
Paolo Cappabianca
Marialaura Del Basso De Caro
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-017-0562-9

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