Expression of PDL-1 and Its Correlation with TIL in Triple Negative Cases of Breast Carcinoma

Neha Sharma; Akashdeep Singh; Arshdeep Kaur; Mridu Manjari

doi:10.21276/apalm.3004

Neha Sharma Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research Amritsar, Punjab. Pin-143001, India
Akashdeep Singh Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research Amritsar, Punjab. Pin-143001, India
Arshdeep Kaur Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research Amritsar, Punjab. Pin-143001, India
Mridu Manjari Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research Amritsar, Punjab. Pin-143001, India

DOI: https://doi.org/10.21276/apalm.3004

Keywords: Programmed death ligand (PD-L1), Carcinoma, Breast, Immunohistochemistry

Abstract

Background: In the present study, we aimed to determine the expression of PDL1 and its correlation with TIL in Triple Negative (ER, PR and Her 2neu negative) cases of breast carcinoma (immune-histochemical study) Methods: Expression of PD-L1 was seen on 40 proven triple negative cases of breast carcinomas (TNBC) and to correlate it with other parameters affecting prognosis of the disease. All the cases were infiltrating ductal carcinoma NOS (not otherwise specified) Result: Maximum cases were Grade III (67.5%) followed by Grade II (32.5%). PD-L1 positivity was seen in 32.5% cases whereas TIL was positive for PD-L1 in 27.5 %. 5 cases were positive for both epithelial cell and TIL. Out of 13 PD-L1 positive tumors, 38.5% cases showed TIL positivity whereas out of 27 PD-L1 negative tumors, only 22.2% were TIL positive. PD-L1 expression in TIL was seen in 38.5% of cases however there was no statistically significant correlation between PD-L1 positivity and TIL positivity. PDL-1 positivity was more in Grade III (33.3%) as compared to Grade II (23%) lesions. Thus, it was observed that PD-L1 positivity increased from grade II to grade III lesions. Conclusion: Intra-tumoral expression of PD-L1 is directly proportional to histological grade, aggressive subtypes in TNBC cases however there was no statistically significant correlation between PD-L1 positivity in tumor cells and TIL positivity. We thus postulate that measurement of PD-L1 expression in TNBC cases could enhance the accuracy of predicting patient prognosis and allow for optimal treatment selection.

References

Patil VW, Singhai R, Patil AV, Gaurav PD. Triple negative (ER, PR, Her2/neu) breast cancer in Indian women. Breast Cancer: Targets and Therapy. 2011;3(2):9ss-19.

Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biol Res. 2017;2;50(1):33.

Khokhar K. Breast Cancer in India: Where do we stand and where do we go. Asian Pacific J Cancer Prev. 2012;13(10):4861-6.

Shetty P. India faces growing breast cancer epidemic. Lancet. 2012 Mar 17;379(9820):992-3.

Gupta S. Breast cancer: Indian experience, data and evidence. South Asian J Cancer. 2016 Sep;5(3):85-6.

Lester SC. The Breast. In: Kumar V, Abbas AK, Fausto N, Aster JC, editors. Robbins and Cotran Pathologic Basis of Disease. 8th ed. Philadelphia. Elsevier; 2010. p. 1066-90.

Allred DC. Ductal carcinoma in situ: terminology, classification and natural history. J Natl Cancer Inst Monogr. 2010 Nov;2010(41):134-8

Rosai J. The Breast. In: Mosby Elsevier. Rosai and Ackerman’s Surgical Pathology. 10th ed (Vol.2). New York; 2005. 1763-1876

Lou J, ZhouY, Huang J, Qian X. Relationship between PD-L1 expression and clinical characteristics in patients with breast invasive ductal carcinoma. Open Med (Wars). 2017; 12: 288–292.

Schutz F, Stefanovic S, Mayer L, Au AV, Domschke C, Sohn C. PD-1/PD-L1 pathway in breast cancer. Oncol Res Treat. 2017;40(5):294-297.

Sznol M, Chen L. Antogonist antibodies to PD-1 and B7-H (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res. 2013 March;19(5):1021-34. PMID: 23460533 DOI: 10.1158/1078-0432.CCR-12-2063.

Kryczek I, Wei S, Gong W, Shu X, Szeliga W, Vatan L. Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development. J Immunol. 2008 Nov 1;181(9):5842-6.

Yang CY, Lin MW, Chang YL, Wu CT, Yang PC. Programmed cell death- ligand 1 expressiom in surgically resected stage 1 pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur J Cancer. 2014 Feb;50(7):1361-9.

Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali HR. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget. 2015 Mar 10;6(7):5449-64.

Devesa SS, Blot WJ, Stone BJ, Miller BA, Tarone RE, Fraumeni JF. Recent cancer trends in United States. J Natl Cancer Inst. 1995 Feb;87(3):175-82.

Hill TD, Khamis HJ, Tyczynski JE, Berkel HJ. Comparison of male and female breast cancer incidence trends, tumor characteristics and survival. Ann Epidemiol [Internet]. 2005 Nov [cited 2019 Aug 2];15(10):773-80. Available from:http://www.annalsofepidemiology.org/ article/S1047-2797(05)00012-8/fulltext DOI:10.1016/ j.annepidem .2005 .01.001

Gouvea AP, Milanezi F, Olson SJ, Leitao D, Schmitt FC, Gobbi H. Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas. Appl Immunohistochem Mol Morphol. 2006 Mar;14(1):103-8.

K Rashmi, Sharma J, Minhas SS, Mardi K. Hormone receptor status of breast cancer in the himalayan region of northern India. Indian J Surg . 2011 Jan;73(1):9-12.

Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with immunoreceptor Tyrosine-based switch motif of Programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004 July;173(2): 945–54.

Rathore A S, Kumar S, Konwar R, Srivastava A N, Makker A, Goel M M. Presence of CD3+ tumour infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast. Indian J Cancer. 2013 Sep;50:239-44.

Rosenberg JE, Censits JH, Powles Tom, Heijden MSV, Balar AV, Necchi A. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum based chemotherapy. Lancet. 2016 May;387(10031):1909-20.

Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS. Predictive correlates of response to the anti-PD-L1 antibody. Nature .2014 Nov;515(7528): 563-7.

Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH. Coinhibitory Pathways in Immunotherapy for Cancer. Annu Rev Immunol. 2016 May;34:539-73.

Kurozumi S, Matasumoto H, Kurosumi M, Inoue K, Fujii T, Horiguchi J. Prognostic significance of tumour infiltrating lymphocytes for oetrogen receptor negative breast cancer without lymph node metastasis. Oncol Lett. 2019 Mar;17(3):2647-56.