Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer
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Background: Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed deathligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC). Methods: We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression-free survival (PFS) were analyzed. Results: PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05). Conclusions: The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.
Abstract
Background: Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed deathligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC). Methods: We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression-free survival (PFS) were analyzed. Results: PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05). Conclusions: The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.
참고문헌 (36)
- Shaffer EA, "Gallbladder cancer : the basics", Gastroenterol Hepatol(N Y), 4, pp.737~741 (2008)
- Goldin RD, "Gallbladder cancer : a morphological and molecular update", Histopathology, 55, pp.218~229 (2009)
- Albores-Saavedra J, "WHO classification of tumours of the digestive system", pp.266~273 (2010), IARC Press
- Aloia TA, "Gallbladder cancer : expert consensus statement", HPB (Oxford), 17, pp.681~690 (2015)
- 위영준, "Trends in Gallbladder Cancer Incidence and Survival in Korea", Cancer Research and Treatment, 50(4), pp.1444~1451 (2018), 대한암학회
- Byung-Woo Kim, "Incidence and Overall Survival of Biliary Tract Cancers in South Korea from 2006 to 2015: Using the National Health Information Database", Gut and Liver, 13(1), pp.104~113 (2019), 거트앤리버 소화기연관학회협의회[DOI]
- Jiao Y, "Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas", Nat Genet, 45, pp.1470~1473 (2013)
- Javle MM, "Identification of unique somatic mutations with functional relevance through genetic characterization of gallbladder cancer(GB ca)", J Clin Oncol, 31(4 Suppl), pp.214~ (2013)
- Wu P, "PD-L1 and survival in solid tumors : a meta-analysis", PLoS One, 10, pp.e0131403~ (2015)
- Pyo JS, "Prognostic role of PD-L1 in malignant solid tumors : a meta-analysis", Int J Biol Markers, 32, pp.e68~74 (2017)
- Neyaz A, "Clinical relevance of PD-L1expression in gallbladder cancer : a potential target for therapy", Histopathology, 73, pp.622~633 (2018)
- Lin J, "Classification of gallbladder cancer by assessment of CD8(+)TIL and PD-L1 expression", BMC Cancer, 18, pp.766~ (2018)
- Takahashi R, "Current status of immunotherapy for the treatment of biliary tract cancer", Hum Vaccin Immunother, 9, pp.1069~1072 (2013)
- Bang YJ, "Pembrolizumab(pembro)for advanced biliary adenocarcinoma : results from the KEYNOTE-028(KN028)and KEYNOTE-158(KN158)basket studies", J Clin Oncol, 37(15 Suppl), pp.4079~ (2019)
- Amin MB, "AJCC cancer staging manual" (2017), Springer
- Schmid P, "Atezolizumab and Nab-paclitaxel in advanced triple-negative breast cancer", N Engl J Med, 379, pp.2108~2121 (2018)
- Motzer RJ, "Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma", N Engl J Med, 380, pp.1103~1115 (2019)
- Giroux Leprieur E, "Immunotherapy revolutionises non-small-cell lung cancer therapy : results, perspectives and new challenges", Eur J Cancer, 78, pp.16~23 (2017)
- Carretero-González A, "Analysis of response rate with ANTI PD1", PD-L1 monoclonal antibodies in advanced solid tumors : a meta-analysis of randomized clinical trials, 2018, pp.9, 8706~8715
- Zhao B, "The benefit and risk of nivolumab in non-small-cell lung cancer : a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials", Cancer Med, 7, pp.1642~1659 (2018)
- Reck M, "Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer", N Engl J Med, 375, pp.1823~1833 (2016)
- Wang X, "PD-L1 expression in human cancers and its association with clinical outcomes", Onco Targets Ther, 9, pp.5023~5039 (2016)
- Fang W, "Association between PD-L1 expression on tumour-infiltrating lymphocytes and overall survival in patients with gastric cancer", J Cancer, 8, pp.1579~1585 (2017)
- Qing Y, "Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer", Drug Des Devel Ther, 9, pp.901~909 (2015)
- Ohigashi Y, "Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer", Clin Cancer Res, 11, pp.2947~2953 (2005)
- Shi SJ, "B7-H1 expression is associated with poor prognosis in colorectal carcinoma and regulates the proliferation and invasion of HCT116 colorectal cancer cells", PLoS One, 8, pp.e76012~ (2013)
- Yang CY, "Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes", Eur J Cancer, 50, pp.1361~1369 (2014)
- Skov BG, "The prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer in an unselected, consecutive population", Mod Pathol, 33, pp.109~117 (2020)
- Walter D, "PD-L1 expression in extrahepatic cholangiocarcinoma", Histopathology, 71, pp.383~392 (2017)
- Gao Q, "Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma", Clin Cancer Res, 15, pp.971~979 (2009)
- Chen CL, "PD-L1 expression as a predictive biomarker for cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma", Oncoimmunology, 5, pp.e1176653~ (2016)
- Zoroquiain P, "Programmed cell death ligand-1 expression in tumor and immune cells is associated with better patient outcome and decreased tumor-infiltrating lymphocytes in uveal melanoma", Mod Pathol, 31, pp.1201~1210 (2018)
- Ha H, "Soluble programmed death-ligand 1(sPDL1)and neutrophil-to-lymphocyte ratio(NLR)predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy", Oncotarget, 7, pp.76604~76612 (2016)
- Diggs LP, "Utility of PD-L1 immunohistochemistry assays for predicting PD-1", PD-L1 inhibitor response, 2017, pp.5, 12~
- Festino L, "Cancer treatment with anti-PD-1", PD-L1 agents : is PD-L1 expression a biomarker for patient selection, 2016, pp.76, 925~945
- O’Malley DP, "Immunohistochemical detection of PD-L1 among diverse human neoplasms in a reference laboratory:observations based upon 62,896 cases", Mod Pathol, 32, pp.929~942 (2019)
