Human Equilibrative Nucleoside Transporter 1 Expression in Endoscopic Ultrasonography-Guided Fine-Needle Aspiration Biopsy Samples Is a Strong Predictor of Clinical Response and Survival in the Patients With Pancreatic Ductal Adenocarcinoma Undergoing Gemcitabine-Based Chemoradiotherapy

Abstract

ObjectivesThis study aimed to clarify whether pretreatment human equilibrative nucleoside transporter (hENT1) expressions in endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) specimens obtained from resectable, borderline resectable, and locally advanced unresectable pancreatic ductal adenocarcinoma (PDAC) are concordant with those in the resected specimen after gemcitabine-based chemoradiotherapy (Gem-CRT) and to validate the utility of hENT1 expression using EUS-FNAB samples as a prognostic marker.MethodsWe evaluated the relationship between hENT1 expressions assessed by immunohistochemical staining and clinical outcomes in 51 of 76 patients with PDAC who were diagnosed by EUS-FNAB and received preoperative Gem-CRT.ResultsThe concordance rate of hENT1 expressions was 89.2% (K = 0.681). Median survival time (month) in the 51 whole patients and 37 patients with resection was significantly longer in hENT1 positive than in hENT1 negative: 25.0 and 30.0 versus 9.0 and 9.0, respectively. A multivariate analysis confirmed that hENT1 expression was an independent prognostic factor in both whole patients and those with resection. Regardless of T3 and T4, hENT1-positive patients with resection had significantly better prognosis than hENT1-negative patients, whose prognosis was similar to those without resection.ConclusionsThe assessment of hENT1 expression using EUS-FNAB samples before Gem-CRT provides important information on patients with PDAC who can benefit from curative-intent resection.

Current and future biomarkers for pancreatic adenocarcinoma

“…These results were corroborated by in vitro experiments, showing an increased sensitivity to gemcitabine in pancreatic cancer cell lines with high hENT1 gene expression. 92 Yamada et al 93 analyzed pre-treatment hENT1 expression levels in EUS-FNA specimens obtained from patients with different stages of PDAC and compared them to resected specimens after gemcitabine-based chemoradiotherapy. They confirmed that hENT1 expression was an independent prognostic factor in all patients and in the subgroup that underwent resection.…”

Combined Analyses of hENT1, TS, and DPD Predict Outcomes of Borderline-resectable Pancreatic Cancer

“…However, the positive predictive values of FNA specimens were relatively high at 71, 80, and 69%, respectively. Yamada et al reported that pretreatment hENT1 expressions in FNA specimens were concordant with those in the resected specimen after GEM-based chemoradiotherapy (32). Further studies are required to confirm the importance of enzyme expression in FNA specimens.…”

Reviewing the Utility of EUS FNA to Advance Precision Medicine in Pancreatic Cancer

“…A recent example of this concept is the retrospective identification of human equilibrative nucleoside transporter-1 (hENT1) expression as a predictive biomarker in PC patients undergoing gemcitabine-based chemotherapy, in this case primarily obtained through immunohistochemistry and quantitative PCR analysis using previously obtained FFPE surgical samples [ 58 , 95 , 96 ]. Yamada, et al reported high concordance between hENT1 expression in baseline EUS FNA samples compared to subsequent surgical specimens in patients receiving neoadjuvant gemcitabine-based chemo–radiotherapy, and confirmed the role of hENT1 in predicting gemcitabine response [ 97 ]. This supports the clinical utility of EUS FNA biopsy in treatment naïve patients, to evaluate the molecular profile of tumours and identify novel biomarkers both before and during treatment.…”