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- Title
High‐resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas.
- Authors
Yoshimoto, Koji; Hatae, Ryusuke; Suzuki, Satoshi O.; Hata, Nobuhiro; Kuga, Daisuke; Akagi, Yojiro; Amemiya, Takeo; Sangatsuda, Yuhei; Mukae, Nobutaka; Mizoguchi, Masahiro; Iwaki, Toru; Iihara, Koji
- Abstract
Craniopharyngioma consists of adamantinomatous and papillary subtypes. Recent genetic analysis has demonstrated that the two subtypes are different, not only in clinicopathological features, but also in molecular oncogenesis. Papillary craniopharyngioma (pCP) is characterized by a <italic>BRAF</italic> mutation, the V600E (Val 600 Glu) mutation. Adamantinomatous craniopharyngioma (aCP) can be distinguished by frequent β‐catenin gene (<italic>CTNNB1</italic>) mutations. Although these genetic alterations can be a diagnostic molecular marker, the precise frequency of these mutations in clinical specimens remains unknown. In this study, we first evaluated <italic>BRAF</italic> V600E and <italic>CTNNB1</italic> mutations in four and 14 cases of pCP and aCP, respectively, using high‐resolution melting analysis followed by Sanger sequencing. The results showed that 100% (4/4) of pCP cases had <italic>BRAF</italic> V600E mutations, while 78% (11/14) of the aCP cases had <italic>CTNNB1</italic> mutations, with these genetic alterations being subtype‐specific and mutually exclusive. Second, we evaluated <italic>BRAF</italic> V600E and CTNNB1 mutations by immunohistochemical analysis (IHC). All pCP cases showed positive cytoplasmic staining with the <italic>BRAF</italic> V600E‐mutant antibody (VE‐1), whereas 86% (12/14) of aCP cases showed positive cytoplasmic and nuclear staining for CTNNB1, suggesting a <italic>CTNNB1</italic> mutation. Only one case of wild‐type <italic>CTNNB1</italic> on the DNA analysis showed immunopositivity on IHC. We did not detect a coexistence of <italic>BRAF</italic> V600E and <italic>CTNNB1</italic> mutations in any single tumor, which indicated that these genetic alterations were mutually exclusive. We also report our modified IHC protocol for VE‐1 staining, and present the possibility that <italic>BRAF</italic> V600E mutations can be used as a diagnostic marker of pCP in the differentiation of Rathke cleft cyst with squamous metaplasia.
- Subjects
CRANIOPHARYNGIOMA; PAPILLARY carcinoma; BRAIN tumor genetics; BRAF genes; GENETIC mutation; METAPLASIA; CATENIN genetics; IMMUNOHISTOCHEMISTRY
- Publication
Neuropathology, 2018, Vol 38, Issue 1, p3
- ISSN
0919-6544
- Publication type
Article
- DOI
10.1111/neup.12408