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Comparison of Endometrial Serous and Gastric HER2 Immunohistochemistry Scoring Schemes in Endometrial Carcinomas With Aberrant p53 Expression: Reproducibility and In Situ Hybridization Correlation

  • 0Department of Pathology, Stanford University, School of Medicine, Stanford, California.
International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists +

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July 10, 2025

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July 10, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

The College of American Pathologists

Area Of Science

  • Oncology
  • Pathology
  • Molecular Diagnostics

Background

  • Recent clinical trials (NCT01367002, DESTINY-PanTumor02) have utilized different scoring systems for HER2 testing in endometrial serous carcinoma, leading to confusion.
  • The College of American Pathologists (CAP) initially supported histotype-specific scoring for HER2 testing in endometrial serous carcinoma.
  • The DESTINY-PanTumor02 trial used CAP gastric scoring, highlighting a need to reconcile different HER2 assessment criteria.

Purpose Of The Study

  • To compare the HER2 immunohistochemistry (IHC) scoring results between the endometrial serous and gastric systems.
  • To evaluate the interobserver agreement and correlation with HER2/Chromosome 17 dual in situ hybridization (DISH) for both scoring schemes.
  • To clarify the discrepancies and similarities between the two HER2 scoring methodologies in endometrial carcinoma.

Main Methods

  • Six observers scored 44 HER2-IHC stained p53-abnormal endometrial carcinoma specimens using tissue microarray (TMA).
  • Specimens were scored using both the endometrial serous (NCT01367002) and gastric (CAP) scoring systems.
  • Interobserver agreement was calculated using kappa statistics, and results were correlated with HER2/Chromosome 17 dual in situ hybridization (DISH).

Main Results

  • High interobserver agreement was observed for both scoring schemes: 81.5% (kappa=0.75) for endometrial serous and 84.6% (kappa=0.79) for gastric.
  • Eight specimens showed discordant scores between the two systems, with notable differences in cases with minimal or limited HER2 staining.
  • The endometrial serous scheme demonstrated better concordance with DISH results compared to the gastric scheme, which had more instances of IHC 3+ without HER2 amplification.

Conclusions

  • Both endometrial serous and gastric HER2-IHC scoring systems exhibit similar interobserver agreement.
  • The endometrial serous scoring scheme appears more concordant with DISH results, particularly in identifying HER2 amplification.
  • Recognition of therapy-specific HER2-IHC scoring is crucial in endometrial carcinomas due to subtle but significant differences between scoring systems.

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