A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness is a condition resulting from an abnormality in the BRCA pathway, in addition to breast cancer susceptibility gene 1 (BRCA1)/BRCA2 mutation, and is currently a focus of interest as a predictive factor for sensitivity to new anticancer drugs for PDAC. Platinum agents and poly (ADP-ribose) polymerase inhibitors are expected to be effective against BRCAness PDAC. Presently, searching for abnormalities in driver genes such as BRCA 1/2 would require considerable time and expense. Therefore, use of the Multiplex Ligation-dependent Prove Amplification (MLPA) method to diagnose BRCAness is advantageous in being a low-cost method that allows for analysis within a short time frame, and may help to make precision medicine a reality for patients with pancreatic cancer.
This study included 20 patients with the largest number of in-specimen pancreatic cancer cells among 40 patients with PDAC continuing from endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) conducted at Kitasato University Hospital. Evaluation of the number of cancer cells was conducted by a pathologist. An unstained preparation was created from formalin-fixed paraffin-embedded (FFPE) PDAC tissue obtained via EUS-FNAB, and DNA was extracted. BRCAness was analyzed using the MLPA method.
A BRCAness diagnosis was possible in 15 of 20 (75%) patients using the MLPA method and FFPE tissue obtained via EUS-FNAB in PDAC. Difficulties in BRCAness analysis occurred in 1 patient due to an insufficient amount of DNA and in 4 patients due to poor DNA quality. BRCAness was diagnosed in 1 of 20 (5%) patients.
BRCAness analysis in PDAC patients was possible with the MLPA method using small FFPE obtained via EUS-FNAB, which we believe is the first study to attempt this. Obtaining low-cost analysis results in a short time frame is a key benefit, suggesting this method may be feasible and important in practicing precision medicine to choose a effective drugs in treting PDCA.
Clinical trial identification
Legal entity responsible for the study
Kitasato University School of Medine, Japan.
Has not received any funding.
All authors have declared no conflicts of interest.