- Design
- Discovery by TCGA mining, then IHC validation across tumour types
- Population
- 187 GEA and oesophageal SCC, 168 colonic adenocarcinomas, and other carcinomas
- Primary outcome
- FOG1 and CDX2 expression by tumour site
- Effect
- FOG1 moderate-high in 91.1% of GEA; negative-low in 92.9% of colonic adenocarcinoma
Mining TCGA data across 29 tumour types, the authors found high FOG1 mRNA only in gastric and oesophageal adenocarcinoma. They then stained 187 gastro-oesophageal adenocarcinomas and oesophageal squamous carcinomas, 168 colonic adenocarcinomas and a range of other tumours.
FOG1 was moderate to high in 91.1% of gastro-oesophageal adenocarcinomas, while CDX2 was negative to low in 51.3%. Only 2.5% were CDX2-positive and FOG1-negative. Colonic adenocarcinomas showed the reverse: 92.9% were FOG1 negative to low. FOG1 was seen in 15.5% of pancreatic and 11.2% of ampullary adenocarcinomas, rarely in breast, lung and ovary, and not at all in many other carcinomas.
For metastatic adenocarcinoma of unknown primary, FOG1 could fill the gap CDX2 leaves in the upper GI tract. It is a single-institution study; pancreatic and ampullary overlap means it will not settle every case, and the antibody is not yet widely validated.
- Consider FOG1 with CDX2 when an adenocarcinoma of unknown primary may be upper GI.
- Read a FOG1-positive, CDX2-negative profile as favouring gastro-oesophageal over colonic origin.
- Remember pancreatic and ampullary tumours can express FOG1.
- Validate the antibody on local controls before using it diagnostically.
Why it matters
Upper GI adenocarcinoma has lacked a sensitive and specific marker, which leaves unknown-primary work-ups open-ended.
Don't overread it
One institution's series — sensitivity and specificity need confirmation in independent cohorts and on small biopsies.
The statistics, in plain English
91% sensitivity for gastro-oesophageal adenocarcinoma is much higher than CDX2's roughly 49% here. The percentages come from whole cases; performance on small biopsies or cytology may be lower.
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