CC BY-NC-ND 4.0 · J Lab Physicians 2022; 14(04): 491-496
DOI: 10.1055/s-0042-1757232
Original Article

Study of PD-L1 Expression with Association of Pathological Factors and Molecular Subtypes in Breast Carcinoma

1   Department of Pathology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
1   Department of Pathology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
1   Department of Pathology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
2   Department of Surgery, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India
› Author Affiliations
Funding None.


Background Programmed death ligand 1 (PD-L1), expressed on cancer cells, shows varied results in the prognosis of breast cancer. This study was conducted to study the expression of PD-L1 in breast carcinoma and to correlate it with pathological, molecular classification and prognostic factors.

Materials and Methods PD-L1 expression was correlated with tumor size, histopathological grade, necrosis, lymphovascular, perineurial invasion, lymph node metastasis, molecular classification, and survival in breast carcinoma cases.

Results Fifty cases were included which showed statistically significant difference of PD-L1 with mean age, tumor size, histopathological grade, lymphovascular emboli, and lymph node metastasis (p < 0.05). Estrogen receptor was strongly positive in 46%, progesterone receptor in 42%, and PD-L1 in 6% of cases. No statistically significant difference between pathological tumor–node–metastasis (TNM) staging and PD-L1 expression (p = 0.354) was observed. Receptor operating characteristic curve analysis showed that at the cutoff of PD-L1 greater than 120, specificity was 56.1%, sensitivity 66.7%, negative predictive value 88.5%, and positive predictive value 25% for predicting living status.

Conclusion PD-L1 is associated with poor prognostic factors including tumor size, histopathological grade, lymphovascular emboli, and lymph node metastasis in breast carcinoma. However, no significant association was observed between PD-L1 and pathological TNM stage or molecular subtypes of breast carcinoma. It is suggested that immunohistochemical reporting of PD-L1 should be standardized so that it is reproducible and reliable for the evaluation of breast carcinoma. Further, larger studies with extended follow-ups are recommended so that the exact role of PD-L1 as a prognostic marker in breast carcinoma could be ascertained.

Authors' Contribution

A.G. and S.C. conceptualized the study. A.G. helped in data curation and original drafting. Formal analysis was done by A.G., S.C., and N.C. and methodology by A.G., S.C., N.C.; and A.A., S.C., and N.C. supervised the study. S.C., N.C., and A.A. contributed to writing review and editing. All authors approved the final manuscript.

Publication History

Article published online:
20 October 2022

© 2022. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

  • References

  • 1 Sung H, Ferlay J, Siegel RL. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (03) 209-249
  • 2 Karpathiou G, Casteillo F, Giroult JB. et al. Prognostic impact of immune microenvironment in laryngeal and pharyngeal squamous cell carcinoma: Immune cell subtypes, immuno-suppressive pathways and clinicopathologic characteristics. Oncotarget 2017; 8 (12) 19310-19322
  • 3 Tan LT, Liu J, Cheng K. et al. Prediction role of tumor infiltrating lymphocytes in triple negative breast cancer patients received the neoadjuvant chemotherapy: a meta analysis. Chemo Open Access 2017; 6: 245
  • 4 Pujani M, Jain H, Chauhan V, Agarwal C, Singh K, Singh M. Evaluation of tumor infiltrating lymphocytes in breast carcinoma and their correlation with molecular subtypes, tumor grade and stage. Breast Dis 2020; 39 (02) 61-69
  • 5 Bour-Jordan H, Esensten JH, Martinez-Llordella M, Penaranda C, Stumpf M, Bluestone JA. Intrinsic and extrinsic control of peripheral T cell tolerance by costimulatory molecules of the CD28/B7 family. Immunol Rev 2011; 241 (01) 180-205
  • 6 Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26: 677-704
  • 7 Woo SR, Turnis ME, Goldberg MV. et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 2012; 72 (04) 917-927
  • 8 Stovgaard ES, Dyhl-Polk A, Roslind A, Balslev E, Nielsen D. PD-L1 expression in breast cancer: expression in subtypes and prognostic significance: a systematic review. Breast Cancer Res Treat 2019; 174 (03) 571-584
  • 9 Guo H, Ding Q, Gong Y. et al. Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors. Breast Cancer Res 2020; 22 (01) 69
  • 10 Pawelczyk K, Piotrowska A, Ciesielska U. et al. Role of PD-L1 expression in non small cell lung cancer and their prognostic significance according to their clinicopathological factors and diagnostic markers. Int J Mol Sci 2019; 20 (04) 824
  • 11 Zheng L. PD-L1 expression in pancreatic cancer. J Natl Cancer Inst 2017; 109 (06) djw304
  • 12 Wang C, Zhu H, Zhou Y. et al. Prognostic value of PD-L1 in breast cancer: a meta analysis. Breast J 2017; 23 (04) 436-443
  • 13 Sabatier R, Finetti P, Mamessier E. et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 2015; 6 (07) 5449-5464
  • 14 Tang P, Tse GM. Immunohistochemical surrogates for molecular classification of breast carcinoma: a 2015 update. Arch Pathol Lab Med 2016; 140 (08) 806-814
  • 15 Amin MB, Greene FL, Edge SB. et al. The eighth edition AJCC cancer staging manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017; 67 (02) 93-99
  • 16 Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 2015; 27 (04) 450-461
  • 17 Herbst RS, Soria JC, Kowanetz M. et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014; 515 (7528): 563-567
  • 18 Rebelatto MC, Midha A, Mistry A. et al. Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma. Diagn Pathol 2016; 11 (01) 95
  • 19 Phillips T, Millett MM, Zhang X. et al. Development of a diagnostic programmed cell death -ligand 1 immunohistochemistry assay for nivolumab therapy in melanoma. Appl Immunohistochem Mol Morphol 2018; 26 (01) 6-12
  • 20 Litvin IE, Paganella MP, Wendland EM, Roehe AV. Prognosis of PD-L1 in human breast cancer: protocol for a systematic review and meta-analysis. Syst Rev 2020; 9 (01) 66
  • 21 Botti G, Collina F, Scognamiglio G. et al. Programmed death ligand 1 (PD-L1) tumor expression is associated with a better prognosis and diabetic disease in triple negative breast cancer patients. Int J Mol Sci 2017; 18 (02) 459
  • 22 Muenst S, Schaerli AR, Gao F. et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 2014; 146 (01) 15-24
  • 23 Mori H, Kubo M, Yamaguchi R. et al. The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer. Oncotarget 2017; 8 (09) 15584-15592
  • 24 Evangelou Z, Papoudou-Bai A, Karpathiou G. et al. PD-L1 expression and tumor infiltrating lymphocytes in breast cancer: clinicopathological analysis in women younger than 40 years old. In Vivo 2020; 34 (02) 639-647
  • 25 Ghebeh H, Mohammed S, Al-Omair A. et al. The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia 2006; 8 (03) 190-198
  • 26 Yazdanpanah P, Alavianmehr A, Ghaderi A. et al. PD-L1 expression in tumor lesions and soluble PD-L1 serum levels in patients with breast cancer: TNBC versus TPBC. Breast Dis 2021; 40 (01) 43-50