We aimed to demonstrate that MYC amplification in adenocarcinomas of the stomach (GC) and gastroesophageal junction (GEJ) is of tumor biological significance and exhibits intratumoral heterogeneity. MYC amplification was analyzed by fluorescence in situ hybridization using whole mount tissue sections obtained from resection specimens of 460 chemotherapy naive (surgery only) and 122 neoadjuvantly treated GC-GEJs. The extent of intratumoral heterogeneity was quantified and a MYC score was established. The number of MYC-amplified tumor cells varied largely ranging from few scattered single cells (< 20 per high power field) up to all tumor cells. MYC score 1 was found in 276 cases (47.4%). Split by cohorts, 199 (43.3%) tumors of the chemotherapy naïve (surgery only) and 77 (63.1%) tumors of the neoadjuvant cohort were sorted into the category MYC Score 1. These tumors were frequently located in the gastroesophageal junction, showed non-diffuse differentiation according to Lauren, and favored male sex. Additionally, correlations with higher T- and N category were observed. Overall survival and tumor-specific survival correlated negatively with the MYC score. MYC amplification is common in GC-GEJ, most often heterogeneously distributed, and associated with reduced therapy response. Most interestingly, MYC amplification is far more common in men, providing evidence for sex-specific disease mechanisms, and in tumors that show little response to neoadjuvant chemotherapy, suggesting a link to therapy resistance.
Biegler et al. (Fri,) studied this question.