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Abnormal p53 and p16 staining patterns distinguish uterine leiomyosarcoma from inflammatory myofibroblastic tumour
Author(s) -
Schaefer IngaMarie,
Hornick Jason L,
Sholl Lynette M,
Quade Bradley J,
Nucci Marisa R,
ParraHerran Carlos
Publication year - 2017
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.13176
Subject(s) - leiomyosarcoma , immunohistochemistry , pathology , staining , biology , leiomyoma , uterus , medicine
Aims Uterine myxoid leiomyosarcoma may show relatively bland histological appearances, despite its aggressive behaviour. Distinguishing uterine leiomyosarcoma from the more indolent inflammatory myofibroblastic tumour ( IMT ), which is amenable to targeted therapies, can be challenging. A significant subset of leiomyosarcomas harbour TP 53 and/or CDKN 2A genomic alterations. Here, we examined the diagnostic value of p53 and p16 immunohistochemistry in the distinction of uterine conventional and myxoid leiomyosarcoma from IMT , in correlation with targeted sequencing of TP 53 and CDKN 2A . Methods and results We performed p53 and p16 immunohistochemistry in 49 tumours, including 23 uterine leiomyosarcomas (12 myxoid, 11 conventional) and 26 IMT (12 uterine, 14 extrauterine). TP 53 and CDKN 2A coding regions were sequenced in 20 cases (four myxoid, 11 conventional uterine leiomyosarcomas; four uterine, one extrauterine IMT ). Abnormal p53 staining patterns (strong/diffuse or null) were observed in six of 12 (50%) myxoid and six of 11 (55%) conventional leiomyosarcomas but none of the IMT ( P < 0.0001), correlating with TP 53 mutation/deletion ( P = 0.0001). P16 loss was detected in five of 10 (50%) myxoid and two of 11 (18%) conventional leiomyosarcomas, but none of the IMT ( P = 0.0005), correlating with CDKN 2A deletion ( P = 0.014). Strong/diffuse p16 staining in six of 21 (29%) leiomyosarcomas and three of 26 (12%) IMT did not correlate with CDKN 2A alterations. Conclusions Abnormal p53 staining and p16 loss are observed frequently in uterine leiomyosarcomas, with 100% specificity and 70% sensitivity against IMT , and correlating with genomic alterations. Conversely, IMT shows normal p53 and p16 staining, highlighting the use of these markers in the differential diagnosis of uterine mesenchymal neoplasms.