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Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer - 02/03/23

Doi : 10.1016/j.clinre.2023.102091 
Furkan Ceylan a, , Deniz Can Guven b, Hakan Taban b, Oktay Aktepe b, Taha Koray Sahin b, Sadettin Kilickap c, Alev Turker b, Erhan Hamaloglu d, Derya Karakoc d, Aynur Isik e, Aytekin Akyol e, f, Suayib Yalcin b, Omer Dizdar c
a Department of Medical Oncology, Ankara City Hospital, Ankara, Turkey 
b Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey 
c Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey 
d Department of General Surgery, Hacettepe University Faculty of Medicine, Ankara, Turkey 
e Hacettepe University Transgenic Animal Technologies Research and Application Center, Ankara, Turkey 
f Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey 

Corresponding author at: Ankara City Hospital, Department of Medical Oncology, Ankara Turkey.Ankara City Hospital, Department of Medical OncologyAnkaraTurkey

Highlights

BRCA1 expression was significantly associated with DFS and OS, but not BRCA2, ATM and P53.
BRCA1, BRCA2, ATM and P53 expressions did not have predictive value for platinum salt-based adjuvant chemotherapy benefit.

El texto completo de este artículo está disponible en PDF.

Abstract

Objective

DNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC.

Patients and Methods

Patients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. 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.

Results

130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48–9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04–3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13–5.48, p = 0.023) and high post-operative CA 19–9 level (>100 IU/ml) (HR:2.61 95% CI 1.40–4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53.

Conclusion

Contrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.

El texto completo de este artículo está disponible en PDF.

Keywords : Resected pancreatic cancer, DNA damage repair, Thrombosis, prognostic


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Vol 47 - N° 3

Artículo 102091- mars 2023 Regresar al número
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