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High‐resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas
Author(s) -
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
Publication year - 2018
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12408
Subject(s) - immunohistochemistry , mutation , microbiology and biotechnology , carcinogenesis , biology , craniopharyngioma , pathology , gene , cancer research , genetics , medicine , endocrinology
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 (p CP ) is characterized by a BRAF mutation, the V 600 E ( V al 600 G lu) mutation. Adamantinomatous craniopharyngioma (a CP ) can be distinguished by frequent β‐catenin gene ( CTNNB 1 ) 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 BRAF V 600 E and CTNNB 1 mutations in four and 14 cases of p CP and a CP , respectively, using high‐resolution melting analysis followed by S anger sequencing. The results showed that 100% (4/4) of p CP cases had BRAF V 600 E mutations, while 78% (11/14) of the a CP cases had CTNNB 1 mutations, with these genetic alterations being subtype‐specific and mutually exclusive. Second, we evaluated BRAF V 600 E and CTNNB 1 mutations by immunohistochemical analysis ( IHC ). All p CP cases showed positive cytoplasmic staining with the BRAF V 600 E ‐mutant antibody ( VE ‐1), whereas 86% (12/14) of a CP cases showed positive cytoplasmic and nuclear staining for CTNNB 1, suggesting a CTNNB 1 mutation. Only one case of wild‐type CTNNB 1 on the DNA analysis showed immunopositivity on IHC . We did not detect a coexistence of BRAF V 600 E and CTNNB 1 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 BRAF V 600 E mutations can be used as a diagnostic marker of p CP in the differentiation of R athke cleft cyst with squamous metaplasia.