The Correlation of PD-L1 Overexpression With Tumor Budding In Cervical Carcinoma
Abstract
Background: Several studies have proven the relationship between PD-L1, which is known as an immunotherapy target, and poor prognosis. The presence of a tumor budding (TB) group tumor outside the main tumor is also associated with a poor prognosis. The purpose of this study was to determine the relationship between PD-L1 and the grade of TB in cervical carcinoma.
Methods: The design of this research is a case-control study with a retrospective approach. The sample is from a paraffin block of the primary cervical cancer tumor from the results of surgery in Balimed Denpasar Hospital between 2020 and 2023. From the statistical formula for the case-control study, a minimum sample of 15 is obtained for the case group with the criteria of high-grade TB, while 15 people were in the control group with low-grade TB. Immunohistochemistry (IHC) PD-L1 is positive if the membrane or cytoplasm is brown, and is negative if there is no brown color on the membrane or cytoplasm. Inferential statistics were used to evaluate the relationship between PD-L1 overexpression and low- and high-grade TB in cervical carcinoma using a chi-square test.
Results: The results of this research revealed (p = 0.273) that there was no correlation between PD-L1 expression and high- and low-grade TB. Overexpression of PD-L1 was associated with a 2.250-fold increased risk of high-grade TB (OR = 2.250 with a 95% confidence interval of 0.103–1.915).
Conclusions: The severity of TB does not correlate with PD-L1 expression. The functions of PD-L1 and other variables in the carcinogenesis of TB development are the cause of this weak association.
Keywords
DOI: 10.33371/ijoc.v18i3.1103
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References
Ministry of Health. Kanker serviks [Internet]. 2020 [cited 2023 Jan 24]. Available from: https://yankes.kemkes.go.id/unduhan/fileunduhan_1610415049_651524.pdf
Savitri F. The Relationship between Sexual Behavior and the Incidence of Invasive Cervical Cancer. FK UNS. 2019;5:1–48.
WHO [Internet]. 2018. WHO Cervical Cancer. Available from: https://www.who.int/cancer/prevention/diagnosis-screening/cervical-cancer/en/
Arbyn M, Weiderpass E, Bruni L, Sanjosé S de, Saraiya M, Ferlay J. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Heal. 2020;8:191–203.
Kumar V, Abbas A., Aster J. Neoplasma. In: Robins and Cotrand: Pathologic Basis of Disease. 9thEd ed. Philladelphia, editor. Elsevier; 2015. 266–377 p.
Yeo-Teh N, Ito Y, Jha S. High-risk human papillomaviral oncogenes E6 and E7 target key cellular pathways to achieve oncogenesis. Int J Mol Sci. 2018;19:1706.
Ferns D, Heeren A, Samuels S, Bleeker M, Gruijl T de, Kenter G. Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases. J Immunother Cancer. 2016;4:78.
Bruni L, Albero G, Serrano B, Mena M, Gómez D, Muñoz J. Human Papillomavirus and Related Diseases in report. Barcelona. ICO/IARC Inf Cent HPV Cancer (HPV Inf Centre). 2018;
Lestari Oki DP, N W A. High Grade Tumor Budding as Strong Additional Predictor of Lymph Node Metastasis in Cervical Carcinoma. United Pharma J cofence. 2021;
Chatterjee D, Bansal V, Malik V, Bhagat R, Punia RS, Handa U. Tumor Budding and Worse Pattern of Invasion Can Predict Nodal Metastasis in Oral Cancers and Associated With Poor Survival in Early-Stage Tumors. 2019;98(310):112–9.
Li H, Xu F, Li S, Zhong A, Meng X, Lai M. The tumor microenvironment : An irreplaceable element of tumor budding and epithelial- mesenchymal transition-mediated cancer metastasis. 2016;6918.
Yao M. Desmoplastic Reaction and Tumor Budding in Cervical Squamous Cell Carcinoma are Prognostic Factors for Distant Metastasis : A Retrospective Study Desmoplastic Reaction and Tumor Budding in Cervical Squamous Cell Carcinoma are Prognostic Factors for Distant Metastasis : A Retrospective Study. 2023;
Gun oh chong, Nora Jee-Young P, Hyung soo H, Junghwan C. International budding: A novel prognostic biomarker for tumor recurrence and a potential predictor of nodal metastasis in uterine cervical cancer. elsevier. 2021;47(12):3182–7.
Sahasrabudhe N, JC V der H, Spaans V, Kenter G, de Kroon C, Bosse T. MGL Ligand Expression Is Correlated to Lower Survival and Distant Metastasis in Cervical Squamous Cell and Adenosquamous Carcinoma. Front Oncol. 2019;9:1–8.
Wenzel A, Beckmann MW, Noske A, Hartmann A, Mehlhorn G, Koch MC. Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix. 2018;(April):93–102.
Max N, Harbaum L, Pollheimer M., Lindtner R., Kornprat P, Langer C. Tumor budding with and without admixed inflamation: two different. 2016;
B C, Xu J, S G, Z W. High grade tumor budding stratifies earlystage cervical cancer with recurrence risk. PLoS One. 2016;11.
.Lu D, Ni Z, Liu X, Feng S, Dong X, Shi X. Beyond T cells: understanding the role of PD-1/PD-L1 in tumor-associated macrophages. J Immunol Res. 2019;
Liu Y, Wu L, Tong R, Yang F, Yin L, Li M. PD-1/PD-L1 Inhibitors in Cervical Cancer. Front Pharmacol. 2019;10:1–8.
O’Malley D, Oaknin A, Monk B, Selle F, Rojas C, Gladieff L. Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. Gynecol Oncol. 2021;163:274–80.
AM AH, Rotman J, Stam A, Pocorni N, Gassama A, Samuels S. Efficacy of PD-1 blockade in cervical cancer is related to a CD8+FoxP3+CD25+ T-cell subset with operational effector functions despite high immune checkpoint levels. J Immunother Cancer. 2019;7:43.
Vanderwalde A, Spetzler D, Xiao N, Gatalica Z, Marshall J. Microsatellity instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11,348 patients. Cancer Med. 2018;7(3):746–56.
Mezache L, Paniccia B, Nyinawabera A, Nuovo G. Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers. Mod Pathol. 2015;28:1594–602.
X M, Z H, F T, L X, J Y. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2010;41:868–876.
Grochot R, Brollo J, Neto F, Tregnago A, Scholze C, Norris R. Expression of PD-L1 in cervical carcinoma and its impact on survival associated with T-cell infiltration and FoxP3 expression. Cancer Manag Res. 2019;
Sun C, Mezzadra R, Schumacher T. Regulation and Function of the PD-L1 Checkpoint. Immunity. 2019;48:434–52.
Wang Y, Li G. PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives. Front Med. 2019;13:438–40.
Rischin D, Gil-Martin M, González-Martin A, Braña I, Hou J, Cho D. PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Gynecol Oncol. 2020;159:322–8.
M Š. PD-1/PD-L1 blockade therapy for tumors with downregulated MHC class I expression. Int J Mol Sci. 2017;18 no 6:1337.
Luo L, Luo X, Chen W, Liang C, Yao S, Huang W. Consistency analysis of programmed death-ligand 1 expression between primary and metastatic non-small cell lung cancer: A retrospective study. J Cancer. 2020;11:974–82.
Nuraini, E B, Nadjib D, Muhammad. Hubungan ekspresi programmed death-ligand 1 (PD-L1) terhadap karsinoma nasofaring non keratinizing squamous cell carcinoma dan subtype keratinizing squamous cell carcinoma. Reseach Artik Dep Patol Anat Fak kedokteran, Univ Sumatera utara, medan, Indones. 2021;
Halil B, Adnan E. MHC Class 1 and PDL-1 Status of Primary Tumor and Lymph Node Metastatic Tumor Tissue in Gastric Cancers. Menderes Univ Med Sch Dep Pathol Aydin, Turkey. 2018;
Davis A, Patel V. . The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J Immunother Cancer. 2019;7(1):278.
Wang Y, Li G. PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives. Front Med. 2019;13:438–50.
Saglam O, Zhou J, Wang X, Conejo-Garcia J. PD-L1 expression correlates with young age and CD8+ TIL density in poorly differentiated cervical squamous cell carcinoma. Int J gynecol Pathol. 2020;39:428–35.
W WY, Song Y, Lu Y, Sun J, Wang H. Increased expression of programmed death (PD)-1 and its ligand PD-L1 correlates with impaired cell-mediated immunity in high-risk human papillomavirus-related cervical intraepithelial neoplasia. Immunology. 2013;22.
Feng Y, Ji W, N NY, Huang Y, Ma X. The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance. Cancer Manag Res. 2018;9:628.
L LS, Mahmoud M, Weaver J, Tijaro-Ovalle N, Christofides A. Targeted deletion of PD-1 in myeloid cells induces antitumor immunity. Sci Immunol. 2020;5.
Xu Q, Wang J, Sun Y, Lin Y, Liu J, Zhuo Y. Efficacy and safety of sintilimab plus anlotinib for PD-L1-Positive recurrent or metastatic cervical cancer: A multicenter, single-arm, prospective phase II trial. J Clin Oncol. 2022;40:179–805.
Luchini C, Bibeau F, Ligtenberg M. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019;30(8):1232–43.
Doroshow D, Bhalla S, Beasley M, Sholl L, Kerr K, Gnjatic S. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2021;18:345–6
Zerdes I, Matikas A, Bergh J, Rassidakis G, Foukakis T. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations. Oncogene. 2018;37:4639–61.
Gu X, Dong M, Liu Z, Mi Y, Yang J, Zhang Z. Elevated PD-L1 expression predicts poor survival outcomes in patients with cervical cancer. Cancer Cell Int. 2019;
Meng Y, H HL, Hu J, Liu S, Hao X, Wong M. PD-L1 expression correlates with tumor infiltrating lymphocytes and response to neoadjuvant chemotherapy in cervical cancer. J Cancer. 2019;9:2938–45.
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