Diverse ‘just-right’ levels of chromosomal instability and their clinical implication in neoadjuvant treated gastric cancer
BACKGROUND The carcinogenic process has been shown to be driven by chromosomal instability or CIN through either gaining or losing parts or even whole chromosomes. The most frequent gastric carcinoma subtype according to the analysis conducted by the Cancer Genome Atlas is CIN. Unlike other gastric carcinoma subtypes such as EBV and high microsatellite instability subtypes, CIN subtypes are poorly characterized. This has been shown to be because of inconsistent techniques that determine CIN precisely in routine diagnostic settings. This study, therefore, aimed to determine the role of molecular classification as a prognosticator and a predictor with an emphasis on CIN in a setting of neoadjuvant chemotherapy of gastric carcinoma. METHOD Tumor specimens from the stomach and gastroesophageal junction were obtained from 617 patients by surgical resection. Out of which, 321 had received CTx while 291 had not. Biopsies were taken from 143 patients before neoadjuvant CTx. Standard assays were used to analyze EBV and MSI-H subtypes while multiplex PCRs analyzing markers of 22 microsatellites were used to detect CIN. CIN was categorized into four subgroups namely low, moderate, substantial, and high. KEY FINDINGS The EBV (+) and MSI-H cohort with or without Rx were found to show increased survival when compared with the cohort with CIN in the resected tumors. Uni and multivariate analysis in the resected tumors after treatment with neoadjuvant CTx revealed that a substantial subgroup of CIN was a negative prognosticator. Regression of the tumor was observed in the high subgroup of CIN in the biopsies taken before treatment. This was thought to be a result of the tumor becoming intolerant to DNA damaging agents after a certain threshold is exceeded. CONCLUSION The findings of this study revealed prognosis of gastric carcinoma in different patient groups may be mapped out with a thorough classification of CIN. This would further guide the management of these patients.
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