Skip to main content

Advertisement

SpringerLink
Log in

Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?

  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (β-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear β-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining, and one PCP showed membranous β-catenin expression and negative BRAF V600E immunostaining. Among the 26 nuclear β-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear β-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, Sakamoto M, Hirohashi S (2002) Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol 161:1997-2001. https://doi.org/10.1016/s0002-9440(10)64477-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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 ER, Jr., Stewart C, Ligon KL, Hoang MP, Van Hummelen P, Hahn WC, Louis DN, Resnick AC, Kieran MW, Getz G, Santagata S (2014) Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet 46:161-165. https://doi.org/10.1038/ng.2868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hofmann BM, Kreutzer J, Saeger W, Buchfelder M, Blumcke I, Fahlbusch R, Buslei R (2006) Nuclear beta-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and rathke cleft cysts: a clinico-pathologic approach. Am J Surg Pathol 30:1595-1603. https://doi.org/10.1097/01.pas.0000213328.64121.12

    Article  PubMed  Google Scholar 

  4. Jones RT, Abedalthagafi MS, Brahmandam M, Greenfield EA, Hoang MP, Louis DN, Hornick JL, Santagata S (2015) Cross-reactivity of the BRAF VE1 antibody with epitopes in axonemal dyneins leads to staining of cilia. Mod Pathol 28:596-606. https://doi.org/10.1038/modpathol.2014.150

    Article  CAS  PubMed  Google Scholar 

  5. Malgulwar PB, Nambirajan A, Pathak P, Faruq M, Suri V, Sarkar C, Jagdevan A, Sharma BS, Sharma MC (2017) Study of beta-catenin and BRAF alterations in adamantinomatous and papillary craniopharyngiomas: mutation analysis with immunohistochemical correlation in 54 cases. J Neuro-Oncol 133:487-495. https://doi.org/10.1007/s11060-017-2465-1

    Article  CAS  Google Scholar 

  6. Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski-Maher T, Flamm ES, Epstein FJ, Miller DC (1994) Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome. Neurosurg 35:1001-1010. https://doi.org/10.1227/00006123-199412000-00001

    Article  CAS  Google Scholar 

  7. Yue Q, Yu Y, Shi Z, Wang Y, Zhu W, Du Z, Yao Z, Chen L, Mao Y (2018) Prediction of BRAF mutation status of craniopharyngioma using magnetic resonance imaging features. J Neurosurg 129:27-34. https://doi.org/10.3171/2017.4.JNS163113

    Article  CAS  PubMed  Google Scholar 

  8. Fujio S, Juratli TA, Arita K, Hirano H, Nagano Y, Takajo T, Yoshimoto K, Bihun IV, Kaplan AB, Nayyar N, Fink AL, Bertalan MS, Tummala SS, Curry WT, Jr., Jones PS, Martinez-Lage M, Cahill DP, Barker FG, Brastianos PK (2019) A Clinical Rule for Preoperative Prediction of BRAF Mutation Status in Craniopharyngiomas. Neurosurgery 85:204-210. https://doi.org/10.1093/neuros/nyy569

    Article  PubMed  Google Scholar 

  9. Himes BT, Ruff MW, Van Gompel JJ, Park SS, Galanis E, Kaufmann TJ, Uhm JH (2018) Recurrent papillary craniopharyngioma with BRAF V600E mutation treated with dabrafenib: case report. J Neurosurg 1:1-5. https://doi.org/10.3171/2017.11.JNS172373

    Article  Google Scholar 

  10. Rostami E, Witt Nystrom P, Libard S, Wikstrom J, Casar-Borota O, Gudjonsson O (2017) Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy. Acta Neurochir 159:2217-2221. https://doi.org/10.1007/s00701-017-3311-0

    Article  PubMed  Google Scholar 

  11. Roque A, Odia Y (2017) BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. CNS Oncol 6:95-99. https://doi.org/10.2217/cns-2016-0034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brastianos PK, Shankar GM, Gill CM, Taylor-Weiner A, Nayyar N, Panka DJ, Sullivan RJ, Frederick DT, Abedalthagafi M, Jones PS, Dunn IF, Nahed BV, Romero JM, Louis DN, Getz G, Cahill DP, Santagata S, Curry WT, Jr., Barker FG, 2nd (2016) Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy. J Natl Cancer Inst 108. https://doi.org/10.1093/jnci/djv31011

  13. Alexandraki KI, Kaltsas GA, Karavitaki N, Grossman AB (2019) The Medical Therapy of Craniopharyngiomas: The Way Ahead. J Clin Endocrinol Metab 104:5751-5764. https://doi.org/10.1210/jc.2019-01299

    Article  PubMed  Google Scholar 

  14. Oka H, Kawano N, Yagishita S, Suwa T, Yoshida T, Maezawa H, Utsuki S, Kameya T, Fujii K (1995) Origin of ciliated craniopharyngioma: pathological relationship between Rathke cleft cyst and ciliated craniopharyngioma. Noshuyo Byori 12:97-103

    CAS  PubMed  Google Scholar 

  15. Marucci G, de Biase D, Zoli M, Faustini-Fustini M, Bacci A, Pasquini E, Visani M, Mazzatenta D, Frank G, Tallini G (2015) Targeted BRAF and CTNNB1 next-generation sequencing allows proper classification of nonadenomatous lesions of the sellar region in samples with limiting amounts of lesional cells. Pituitary 18:905-911. https://doi.org/10.1007/s11102-015-0669-y

    Article  CAS  PubMed  Google Scholar 

  16. Yoshimoto K, Hatae R, Suzuki SO, Hata N, Kuga D, Akagi Y, Amemiya T, Sangatsuda Y, Mukae N, Mizoguchi M, Iwaki T, Iihara K (2018) High-resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas. Neuropathology 38:3-10. https://doi.org/10.1111/neup.12408

    Article  CAS  PubMed  Google Scholar 

  17. Preda V, Larkin SJ, Karavitaki N, Ansorge O, Grossman AB (2015) The Wnt signalling cascade and the adherens junction complex in craniopharyngioma tumorigenesis. Endocr Pathol 26:1-8. https://doi.org/10.1007/s12022-014-9341-8

    Article  CAS  PubMed  Google Scholar 

  18. Hama S, Arita K, Nishisaka T, Fukuhara T, Tominaga A, Sugiyama K, Yoshioka H, Eguchi K, Sumida M, Heike Y, Kurisu K (2002) Changes in the epithelium of Rathke cleft cyst associated with inflammation. J Neurosurg 96:209-216. https://doi.org/10.3171/jns.2002.96.2.0209

    Article  PubMed  Google Scholar 

  19. Kim JH, Paulus W, Heim S (2015) BRAF V600E mutation is a useful marker for differentiating Rathke’s cleft cyst with squamous metaplasia from papillary craniopharyngioma. J Neuro-Oncol 123:189-20. https://doi.org/10.1007/s11060-015-1757-6

    Article  Google Scholar 

  20. Okada T, Fujitsu K, Ichikawa T, Mukaihara S, Miyahara K, Kaku S, Uryuu Y, Niino H, Yagishita S, Shiina T (2012) Coexistence of adamantinomatous and squamous-papillary type craniopharyngioma: case report and discussion of etiology and pathology. Neuropathology 32:171-173. https://doi.org/10.1111/j.1440-1789.2011.01235.x

    Article  PubMed  Google Scholar 

  21. Larkin SJ, Preda V, Karavitaki N, Grossman A, Ansorge O (2014) BRAF V600E mutations are characteristic for papillary craniopharyngioma and may coexist with CTNNB1-mutated adamantinomatous craniopharyngioma. Acta Neuropathol 127:927-929. https://doi.org/10.1007/s00401-014-1270-6

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported in part by a grant from the Foundation for Growth Science.

Author information

Authors and Affiliations

  1. Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo, Japan

    Noriaki Fukuhara, Naoko Inoshita, Hirokazu Fukuhara, Mitsuo Yamaguchi-Okada, Shozo Yamada & Hiroshi Nishioka

  2. Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Noriaki Fukuhara, Naoko Inoshita & Masanobu Kitagawa

  3. Okinaka Memorial Institute for Medical Research, Tokyo, Japan

    Noriaki Fukuhara, Naoko Inoshita, Akira Takeshita, Yasuhiro Takeuchi, Shozo Yamada & Hiroshi Nishioka

  4. Department of Functional Morphology, Niigata University of Pharmacy and Applied life Sciences, Niigata, Japan

    Takeo Iwata

  5. Department of Medical Pharmacology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan

    Takeo Iwata & Katsuhiko Yoshimoto

  6. Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan

    Naoko Inoshita

  7. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan

    Keita Tatsushima, Akira Takeshita & Yasuhiro Takeuchi

  8. Department of Pediatrics, Toranomon Hospital, Tokyo, Japan

    Junko Ito

  9. Department of Neurosurgery, Tokyo Neurological Center, Tokyo, Japan

    Shozo Yamada

Authors
  1. Noriaki Fukuhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeo Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naoko Inoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katsuhiko Yoshimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masanobu Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hirokazu Fukuhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Keita Tatsushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mitsuo Yamaguchi-Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akira Takeshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Junko Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yasuhiro Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shozo Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hiroshi Nishioka
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Noriaki Fukuhara, Takeo Iwata, Naoko Inoshita, Katsuhiko Yoshimoto, Hirokazu Fukuhara, Keita Tatsushima, Mitsuo Yamaguchi-Okada, Akira Takeshita, Junko Ito, Yasuhiro Takeuchi, Shozo Yamada, and Hiroshi Nishioka. The first draft of the manuscript was written by Noriaki Fukuhara and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Naoko Inoshita.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Statement

This study is a retrospective case series and was approved by the institutional review board of Toranomon Hospital (No. 1616) and Tokushima University (No. 714-2).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fukuhara, N., Iwata, T., Inoshita, N. et al. Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?. Endocr Pathol 32, 262–268 (2021). https://doi.org/10.1007/s12022-020-09644-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12022-020-09644-z

Keywords

Search

Navigation