The edition · Pathology
MMR status in prostate cancer differed between foci in over half of multi-block cases
Mismatch repair deficiency sat in the highest-grade focus, so that is the block to stain; FOG1 marks gastro-oesophageal adenocarcinoma where CDX2 fails; nanopore methylation matched arrays at family level in paediatric CNS tumours; and a stepwise panel separates metaplastic breast carcinoma from cutaneous SCC.
The edition in brief
In 32 treatment-naive mismatch repair-deficient prostate cancers from one institution, MMR immunohistochemistry on multiple blocks in 14 cases showed discordant status between foci in 8 (57%), with deficiency always confined to the highest-grade focus. Most losses were MSH2/MSH6, cribriform or intraductal pattern was present in 78%, and a third of those germline-tested had Lynch syndrome. FOG1 immunohistochemistry was moderate to high in 91.1% of gastric and oesophageal adenocarcinomas, where CDX2 was negative to low in 51.3%; it was absent in oesophageal squamous carcinoma and negative to low in 92.9% of colonic adenocarcinomas, though present in some pancreatic and ampullary cancers. In 23 paediatric tumours profiled on both Oxford Nanopore and Illumina EPIC arrays, nanopore classification agreed with integrated histology at family level in all CNS cases, MGMT status matched in 16 of 17, and the pan-cancer model performed poorly outside the CNS. A comparison of 15 metaplastic breast carcinomas with squamous differentiation and 18 cutaneous SCCs of breast and chest skin found CK7, SOX10 and TRPS1 more frequent in breast primaries, PIK3CA alterations in breast and NOTCH1 mutations and UV signatures only in skin.
FOG1 stained nine in ten gastro-oesophageal adenocarcinomas where CDX2 missed half
FOG1 is a promising upper GI adenocarcinoma marker to pair with CDX2 for unknown primaries, once validated locally.
Same-day nanopore methylation matched arrays at family level in paediatric CNS tumours
Nanopore methylation is reliable for same-day family-level classification of paediatric CNS tumours; arrays still edge it at class level.
CK7, SOX10 and TRPS1 favour breast origin in a squamous carcinoma of the chest
For a squamous carcinoma of the breast or chest of uncertain origin, use CK7, SOX10 and TRPS1 first, and UV signature and NOTCH1 on sequencing if needed.
When a biomarker drives treatment, stain the worst block
Stain the highest-grade focus for predictive markers, and state in the report which block was tested.
In multifocal prostate cancer, test MMR on the highest-grade focus
When assessing MMR status in multifocal prostate cancer, stain the highest-grade focus, and refer deficient cases for germline testing.
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