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What Therapeutic Biomarkers in Gastro-Esophageal Junction and Gastric Cancer Should a Pathologist Know About?

Marian Priyanthi Kumarasinghe1, Daniel Houghton2, Benjamin Michael Allanson2

  • 1Anatomical Pathology, PathWest, QEII Medical Centre, School of Pathology and Laboratory Medicine, UWA and Curtin Medical School, J Block, Hospital Avenue, Nedlands, Western Australia 6009, Australia.

Surgical Pathology Clinics
|October 20, 2023
PubMed

Insights

Gastrointestinal cancers require molecular testing for targeted therapies. HER2 testing is recommended for gastro-esophageal junction adenocarcinomas, with optional testing for PD-L1 and mismatch repair protein status.

Area of Science:

  • Oncology
  • Gastroenterology
  • Molecular Pathology

Background:

  • Upper gastrointestinal malignancies are aggressive, often requiring multimodal treatment.
  • Current treatments incorporate targeted therapies based on tumor biomarkers.
  • Biomarker testing is crucial for personalized cancer care.

Purpose of the Study:

  • To outline essential molecular testing strategies for upper gastrointestinal cancers.
  • To emphasize the importance of HER2, PD-L1, and mismatch repair protein status assessment.
  • To guide pathologists and clinicians on optimal testing methodologies.

Main Methods:

  • Recommended reflex HER2 testing for all gastro-esophageal junction cancers.
  • Optional testing for PD-L1 and mismatch repair protein status.
  • Utilizing immunohistochemistry, in-situ hybridization, and next-generation sequencing (NGS).

Main Results:

  • HER2 testing is mandatory for gastro-esophageal junction adenocarcinomas.
  • NGS can simultaneously assess multiple molecular events, including HER2 amplification and MSS status.
  • Pathologist expertise in preanalytical, analytical, and scoring aspects is vital.

Conclusions:

  • Comprehensive molecular profiling, including HER2, PD-L1, and mismatch repair status, is essential for guiding therapy in upper GI cancers.
  • Standardized and validated testing methods are critical for accurate results.
  • Genomic profiling offers a simultaneous assessment of various clinically relevant molecular alterations.
Keywords:
BiomarkersGastric/GEJHER2MMRPPD L1

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