Clinical relevance of PD‐L1 expression in gallbladder cancer: a potential target for therapy

• Published in: Histopathology 2018-10, Vol.73 (4), p.622-633
• Main Authors: Neyaz, Azfar, Husain, Nuzhat, Kumari, Swati, Gupta, Sameer, Shukla, Saumya, Arshad, Sanya, Anand, Nidhi, Chaturvedi, Arun
• Format: Article
• Language: English
• Subjects: Adult; Aged; Apoptosis; B7-H1 Antigen - biosynthesis; Biomarkers, Tumor - analysis; Disease-Free Survival; Female; Gallbladder cancer; Gallbladder Neoplasms - mortality; Gallbladder Neoplasms - pathology; Humans; Immune checkpoint inhibitors; Kaplan-Meier Estimate; Lymph nodes; Lymphatic system; Lymphocytes; Male; Metastases; Metastasis; Middle Aged; Neoplasia; PD-L1 protein; Prognosis; Tumors
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.13669

Aims Programmed death‐ligand 1 (PD‐L1), a potential target for immune checkpoint inhibitors in various solid neoplasms, has been studied in very few cases of Gall Bladder Carcinoma (GBC). The current study aimed to evaluate PD‐L1 expression at primary and metastatic sites of GBC, and its associations with standard prognostic clinicopathological parameters, as well as with overall survival. Methods and results One hundred and seventy‐four cases of GBC were evaluated for PD‐L1 expression by the use of the SP263 clone in tissue microarrays. Clinicopathological characteristics and survival data were correlated with PD‐L1 expression analysed at different cut‐offs of ≥1%, ≥10% and ≥50% in tumour cells and tumour‐infiltrating lymphocytes (TILs). The mean age of patients was 49.9 years, and the male/female ratio was 1:2.9. Of the cases, 73.6% presented with stage 3/4 disease. Tumour cells expressed PD‐L1 in 23.0% of cases, and TILs expressed PD‐L1 in 24.1% of cases. At a cut‐off of 10%, 14.9% of cases expressed PD‐L1, and at a cut‐off of 50%, 7.5% of cases expressed PD‐L1. Significant associations were seen between tumour proportion score and histological type (P = 0.004), histological grade (P = 0.004), nuclear grade (P = 0.008), nodal metastasis (P = 0.051), higher stage (P = 0.058), and TILs (P < 0.001). Tumour size, growth pattern, the presence of necrosis and lymphovascular emboli showed no significant associations with PD‐L1 in tumour cells or TILs. In synchronous paired samples from primary and metastatic lymph nodes, discordantly higher PD‐L1 expression was evident in lymph nodes. Overall survival was not associated with PD‐L1 expression (P = 0.546). Conclusion PD‐L1 does not appear to be a prognostic marker or influence survival in GBC patients. However, PD‐L1 expression occurs in one of four GBCs, supporting the future possibility of immune‐modulation therapy to improve the dismal overall survival.