120P - Clinical implication of DNA damage response gene in advanced gastric cancer stage IV and recurrent gastric cancer patients after gastrectomy treated palliative chemotherapy

Background

This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and clinical outcomes of patients with in gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated palliative 1st line chemotherapy.

Methods

A total of 611 gastric cancer patients had undergone D2 radical gastrectomy at the Chung-Ang University Hospital, between January 2005 and December 2017. In this study, 72 patients after gastrectomy treated palliative chemotherapy were enrolled. We performed the immunohistochemical assessment of MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded (FFPE) samples. In addition, Kaplan-Meier survival analysis and Cox regression models were used to evaluate for independent predictors of overall survival (OS) and progression-free survival (PFS).

Results

Among the 72 patients studied, on immunohistochemical staining, deficient DNA mismatch repair (dMMR) was observed in 19.4% (n = 14). The most common DDR gene whose expression was suppressed was PARP-1 (n = 41, 56.9%), followed by ATM (n = 26, 36.1%), ARID1A (n = 10, 13.9%), MLH1 (n = 12, 16.7%), BRCA1 (n = 11, 15.3%), and MSH2 (n = 3, 4.2%). HER2 (n = 6, 8.3%) and PD-L1 (n = 3, 4.2%) were expressed in 72 patients. The dMMR group exhibited a significantly longer median OS than the MMR-proficient (pMMR) group (19.9 months vs. 11.0 months; HR 0.472, 95% CI = 0.260-1.008, P = 0.032). The dMMR group exhibited a significantly longer median PFS than the pMMR group (7.0 months vs. 5.1 months; HR= 0.498, 95% CI = 0.267-0.928, P = 0.028).

Conclusions

The dMMR group in gastric cancers stage IV and recurrent gastric cancer after gastrectomy have better survivals than the pMMR group. Although dMMR is a predictive factor of immunotherapy in advanced gastric cancer, further studies are needed to determine whether it can be a prognostic factor in gastric cancer patients treated with palliative cytotoxic chemotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.