Expression of therapy target molecules in esophagogastric junction and Barrett's adenocarcinoma

Area of Science:

• Gastroenterology
• Oncology
• Molecular Pathology

Background:

• Novel molecular targeted therapies are emerging for gastric and esophageal adenocarcinomas.
• This study investigates therapeutic target molecule status in esophagogastric junction (EGJ) and Barrett's adenocarcinoma.

Purpose of the Study:

• To assess the expression of key molecular targets in EGJ and Barrett's adenocarcinomas.
• To correlate target molecule expression with patient survival outcomes.
• To determine eligibility for molecular targeted therapies in these cancer types.

Main Methods:

• Tissue microarrays from 114 EGJ and 30 Barrett's adenocarcinomas were analyzed.
• Immunohistochemistry was performed for mismatch repair proteins, PD-L1, HER2, CLDN18, FGFR2b, and EBER-ISH.
• HER2 gene amplification was assessed via in situ hybridization for equivocal cases.

Main Results:

• High rates of target molecule expression were observed: PD-L1 (61.4% EGJ, 76.7% Barrett's), CLDN18 (33.3% EGJ, 23.3% Barrett's), and HER2 (9.6% EGJ, 20.0% Barrett's).
• PD-L1 expression (Combined Positive Score [CPS] ≥ 1) correlated with significantly longer recurrence-free and overall survival.
• Over 80% of both EGJ and Barrett's adenocarcinomas expressed at least one target molecule.

Conclusions:

• The majority of esophagogastric junction and Barrett's adenocarcinomas show potential eligibility for molecular targeted therapies.
• Patient stratification using molecular testing is crucial for implementing precision medicine in these cancers.
• PD-L1 expression serves as a potential predictive biomarker for treatment response and survival.