Abstract 1546P
Background
DNA damage repair (DDR) mutations gained interest in the treatment of patients with metastatic pancreatic cancer (PC), but their relevance in adjuvant setting is unknown. We aimed to assess the prognostic role of tumoral expression of DDR proteins along with patient and tumor characteristics in patients with resectable PC.
Methods
Patients with PC who underwent curative resection in our institution between 2005 and 2017 were retrospectively assessed. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed. BRCA2 staining failed despite repeated testing.
Results
130 patients were included in the study. Median age was 61 and 66% were males. Most of the tumors were located on the pancreatic head and neck (81 %). Lymph node metastasis was present in 57% and vascular invasion was observed in 22 patients (17%). Thrombosis at the time of diagnosis was detected in 25 patients (19%). Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. Patients with an abnormal tumoral p53 expression had longer OS (23.1 vs 15.5 months, p=0.034) and DFS (14.1 vs 9.2 months, p=0.025) compared to patients with normal p53 expression. The OS and DFS were similar in patients with and without loss of tumoral expression of BRCA1 or ATM. In multivariate analysis, higher disease stage (HR 3.1, 95% CI 1.30-7.50, p=0.014), higher post-operative CA 19-9 levels (HR 2.4, 95% CI 1.30-4.30, p=0.003), presence of vascular invasion (HR 3.2, 95% CI 1.50-6.80, p=0.002) were associated with shorter DFS. Higher disease stage (HR 3.5, 95% CI 2.0-6.30, p=0.004), higher post-operative CA19-9 levels (HR 3.2, 95% CI 1.70-5.80, p<0.001), presence of thrombosis (HR 2.2, 95% CI 1.20-4.1, p=0.017) were associated with shorter OS.
Conclusions
The prognostic role of tumoral DDR protein expression with IHC in resected PC is yet to be defined. Other than p53, their contribution seemed to be limited in our study.
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.