ArticleVirchows Archiv : an international journal of pathology2026
H3.3G34W immunohistochemistry negative giant cell tumour of bone. Extended analysis of 35 such cases from a single institution in India.
Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Giant cell tumor of the pubic bone with concomitant enchondroma: a case report.Frontiers in medicine · 2026Article
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Abstract
Though anti-histone H3.3G34W antibody is highly sensitive to giant cell tumours of bone, a subset of tumours which are negative on immunohistochemistry harbours variant H3F3A mutations. In this study, the diagnostic utility of anti-histone H3.3G34V and R immunohistochemistry was assessed along with H3F3A gene mutation analysis by Sanger sequencing. This study also attempted to establish an algorithmic approach to analysis of H3.3G34W immunohistochemically negative tumours. Immunohistochemistry was performed using anti-histone H3.3G34R and anti-histone H3.3G34V antibodies in 35 anti-histone H3.3G34W IHC negative tumours. Simultaneously, all the tumours were subjected to Sanger sequencing to detect mutations in H3F3A gene. Of the 35 tumours tested, 14 showed positive staining for H3.3G34V and one for H3.3G34R immunohistochemistry. Gene mutation analysis by sequencing detected 3 additional cases of H3.3G34W mutation not detected by immunohistochemistry. Of the 14 tumours with H3.3G34V immunohistochemical expression, 11 showed corresponding H3.3G35V mutation on sequencing and a single tumour with H3.3G34R expression showed corresponding H3.3G35R mutation. In addition, sequencing detected 5 cases of H3.3G35L mutation which were negative on immunohistochemistry. Combining immunohistochemistry and sequencing results for the overall 309 GCTBs diagnosed during the study period, the most frequent H3F3A gene mutation was H3.3G34W/H3.3G35W (277/309, 89.6%). Other variants included H3.3G34V/H3.3G35V (14/309,4.5%), H3.3G34L/H3.3G35L (5/309,1.6%), and H3.3G34R/H3.3G35R (1/309,0.3%), while 3.9% (12/309) had the wild-type gene. Immunohistochemistry with H3.3 G34W, H3.3 G34R and G34V can be used as a surrogate for detection of corresponding H3F3A gene mutations. These antibodies should be used as first-line tests for confirming the diagnosis with sequencing being restricted only to tumors negative on immunohistochemistry.
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