Synapse - Immunohistochemical assessment of HRAS Q61R mutations in breast adenomyoepitheliomas

Immunohistochemical assessment of HRAS Q61R mutations in breast adenomyoepitheliomas Journal Article

Authors:	Pareja, F.; Toss, M. S.; Geyer, F. C.; da Silva, E. M.; Vahdatinia, M.; Sebastiao, A. P. M.; Selenica, P.; Szatrowski, A.; Edelweiss, M.; Wen, H. Y.; Mihai, R.; Varga, Z.; Foschini, M. P.; Rubin, B. P.; Ellis, I. O.; Chandarlapaty, S.; Jungbluth, A. A.; Brogi, E.; Weigelt, B.; Reis-Filho, J. S.; Rakha, E. A.
Article Title:	Immunohistochemical assessment of HRAS Q61R mutations in breast adenomyoepitheliomas
Abstract:	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. © 2020 The Authors. Histopathology published by John Wiley & Sons Ltd
Keywords:	immunohistochemistry; clinical article; controlled study; human tissue; gene sequence; human cell; somatic mutation; clinical feature; histopathology; comparative study; sensitivity and specificity; breast; gene locus; immunoreactivity; phosphatidylinositol 3 kinase; oncogene h ras; breast tumor; cell membrane; mitosis rate; ras protein; estrogen receptor; breast carcinogenesis; cell organelle; breast necrosis; myoepithelium; mitosis index; massively parallel sequencing; hras; adenomyoepithelioma; sanger sequencing; human; priority journal; article
Journal Title:	Histopathology
Volume:	76
Issue:	6
ISSN:	0309-0167
Publisher:	Wiley Blackwell
Date Published:	2020-05-01
Start Page:	865
End Page:	874
Language:	English
DOI:	10.1111/his.14057
PUBMED:	31887226
PROVIDER:	scopus
PMCID:	PMC7225035
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084499278&doi=10.1111%2fhis.14057&partnerID=40&md5=8b8b53cd465fbbd001b237be94319b7e
Notes:	Article -- Export Date: 1 June 2020 -- Source: Scopus