Heterogeneous target protein expression in synchronous multiple gastric carcinomas

Area of Science:

• Gastroenterology
• Oncology
• Molecular Pathology

Background:

• Synchronous multiple gastric carcinomas (SMGCs) present unique diagnostic and therapeutic challenges.
• Understanding the molecular landscape of individual tumors within SMGCs is crucial for personalized treatment strategies.

Purpose of the Study:

• To investigate the protein expression levels of HER2, EGFR, and MET across separate tumor lesions in patients diagnosed with SMGCs.
• To assess the degree of intertumoral heterogeneity for these key target proteins within individual SMGC cases.

Main Methods:

• Immunohistochemistry was employed to analyze HER2, EGFR, and MET protein expression.
• The study included 282 carcinomas from 141 patients with SMGCs.

Main Results:

• HER2, EGFR, and MET protein overexpression was observed in 11.3%, 23.4%, and 14.9% of SMGC cases, respectively.
• High intertumoral heterogeneity was noted, with concordance rates below 0.3 kappa for HER2 (90.8%), EGFR (81.6%), and MET (86.5%) expression between synchronous tumors.
• Specific heterogeneity rates were 81.3% for HER2, 78.8% for EGFR, and 90.5% for MET in cases with overexpression in multiple tumors.

Conclusions:

• A considerable intertumoral heterogeneity in target protein expression exists within SMGCs.
• These findings support a multicentric origin hypothesis for SMGC.
• Comprehensive immunohistochemical evaluation of all synchronous gastric lesions is recommended for accurate patient management.