HER2 Intratumoral Heterogeneity

Characterizing HER2 IHC interpretation in gastric and gastroesophageal carcinoma — agreement, heterogeneity, and IHC/ISH discordance.

Purpose

HER2 scoring in gastric/GEJ carcinoma is harder than in breast: more intratumoral heterogeneity, more fixation variability, and a different scoring rubric. This project characterizes HER2 interpretation at Memorial across those dimensions.

Data used

Gastric and GEJ resections and biopsies with HER2 IHC and reflex ISH; de-identified scanned slides on the Memorial share; QuPath annotations exported as GeoJSON per the group SOP.

Methods

Four objectives: inter-observer agreement on HER2 IHC scoring among department pathologists; WSI-level annotation mapping of intratumoral HER2 heterogeneity; correlation and discordance between IHC and ISH; identification of cases where biopsy and resection scoring diverge. Agreement statistics via meddecide (kappa, weighted kappa, ICC).

Current state / open questions

Cohort identification complete; IHC/ISH database curated; agreement study pilot scoring round complete; heterogeneity annotation in QuPath active; manuscript outline drafted. Documented pitfalls: HER2 scoring rules differ between biopsy (focal positivity accepted) and resection, so the two must never be aggregated without the specimen-type column; slide-level tumor percentage matters for downstream heterogeneity metrics, so the tumor-area annotation cannot be skipped even when the HER2 score alone is the question.

Derived from: morphology/her2gastro.qmd.