Abstract
BackgroundAnti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue. MethodsAmong 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation. ResultsThe biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with > 10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10). ConclusionsBiopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates.
Highlights
Intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder carcinoma (GBC) are known biliary tract neoplasms arising from bile duct epithelial cells, collectively termed biliary tract cancer (BTC). 1,2 Neuroendocrine carcinomas (NECs) rarely originate from the endocrine cells of the biliary tract, 3 whereas ampullary carcinomas (ACs) arise from epithelial cells in the papilla area
PD-L1 is a ligand expressed on tumor cells and infiltrating immune cells to which programmed death-1 (PD-1) receptors bind. 8–11 Recently, therapeutic antibodies against PD1/PD-L1 have become available, to which approximately 20–30% of patients with several solid tumors, including bile duct neoplasms, have shown an effective tumor response. 12,13 In particular, patients with highfrequency microsatellite instability (MSI-H) and deficient DNA mismatch repair (MMR) have demonstrated notable response to immune checkpoint inhibitors (ICIs). only 3.0% of those with solid tumors presented with MSI-H
Extensive studies on PD-L1 immunohistochemistry (IHC) have found it to be a viable predictive marker. 16–19 Previous results in patients with BTC have indicated that PD-L1 expression was associated with advanced stage and poor survival. 20–23 no study has established whether PD-L1 expression can be utilized as a biomarker for predicting the therapeutic effect of ICIs. 24–26 KEYNOTE-158 showed that PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34) had an objective response rate (ORR) of 6.6% (4/61) and 2.9% (1/34), respectively, with no significant difference between both groups
Summary
Intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder carcinoma (GBC) are known biliary tract neoplasms arising from bile duct epithelial cells, collectively termed biliary tract cancer (BTC). 1,2 Neuroendocrine carcinomas (NECs) rarely originate from the endocrine cells of the biliary tract, 3 whereas ampullary carcinomas (ACs) arise from epithelial cells in the papilla area. 1,2 Neuroendocrine carcinomas (NECs) rarely originate from the endocrine cells of the biliary tract, 3 whereas ampullary carcinomas (ACs) arise from epithelial cells in the papilla area These tumors are pathologically diagnosed based on biopsy specimens obtained using endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound fine-needle aspiration (EUS-FNA) or abdominal ultrasonography (US) guided transhepatic needle biopsy. Previous studies on PD-L1 expression by tumors and associated inflammatory cells utilized excised specimens and defined PD-L1 positivity as a combined positive score of ≥ 1%. 24,25 Given that the majority of biliary tract neoplasms are diagnosed at an advanced stage, evaluating PD-L1 expression without excision would certainly be beneficial for patients. Methods Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. Conclusions Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates
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