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Immunohistochemical assessment of HRAS Q61R mutations in breast adenomyoepitheliomas
Author(s) -
Pareja Fresia,
Toss Michael S,
Geyer Felipe C,
Silva Edaise M,
Vahdatinia Mahsa,
Sebastiao Ana Paula M,
Selenica Pier,
Szatrowski Austin,
Edelweiss Marcia,
Wen Hannah Y,
Mihai Raluca,
Varga Zsuzsanna,
Foschini Maria P,
Rubin Brian P,
Ellis Ian O,
Chandarlapaty Sarat,
Jungbluth Achim A,
Brogi Edi,
Weigelt Britta,
ReisFilho Jorge S,
Rakha Emad A
Publication year - 2020
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14057
Subject(s) - hras , immunohistochemistry , biology , cancer research , microbiology and biotechnology , mutation , immunology , gene , genetics , kras
Aims Breast adenomyoepitheliomas (AMEs) are uncommon tumours. Most oestrogen receptor (ER)‐positive AMEs have mutations in phosphoinositide 3‐kinase (PI3K) pathway genes, whereas ER‐negative AMEs usually harbour concurrent mutations affecting the HRAS Q61 hotspot and PI3K pathway genes. Here, we sought to determine the sensitivity and specificity of RAS Q61R immunohistochemical (IHC) analysis for detection of HRAS Q61R mutations in AMEs. Methods and results Twenty‐six AMEs (14 ER‐positive; 12 ER‐negative) previously subjected to massively parallel sequencing ( n = 21) or Sanger sequencing ( n = 5) of the HRAS Q61 hotspot locus were included in this study. All AMEs were subjected to IHC analysis with a monoclonal (SP174) RAS Q61R‐specific antibody, in addition to detailed histopathological analysis. Nine ER‐negative AMEs harboured HRAS mutations, including Q61R ( n = 7) and Q61K ( n = 2) mutations. Five of seven (71%) AMEs with HRAS Q61R mutations were immunohistochemically positive, whereas none of the AMEs lacking HRAS Q61R mutations ( n = 17) were immunoreactive. RAS Q61R immunoreactivity was restricted to the myoepithelium in 80% (4/5) of cases, whereas one case showed immunoreactivity in both the epithelial component and the myoepithelial component. RAS Q61R immunohistochemically positive AMEs were associated with infiltrative borders ( P < 0.001), necrosis ( P < 0.01) and mitotic index in the epithelial ( P < 0.05) and myoepithelial ( P < 0.01) components. RAS Q61R IHC assessment did not reveal Q61K mutations (0/2). Conclusions IHC analysis of RAS Q61R shows high specificity (100%) and moderate sensitivity (71%) for detection of HRAS Q61R mutations in breast AMEs, and appears not to detect HRAS Q61K mutations. IHC analysis of RAS Q61R may constitute a useful technique in the diagnostic workup of ER‐negative AMEs.