open access

Vol 95, No 4 (2024)
Research paper
Published online: 2023-10-23
Get Citation

Expression of B7–H4 in endometrial cancer and its impact on patients’ prognosis

Katarzyna Gorzelnik1, Anna Wasaznik-Jedras2, Lukasz Wicherek1, Sebastian Szubert3
·
Pubmed: 37873922
·
Ginekol Pol 2024;95(4):252-258.
Affiliations
  1. Centre of Postgraduate Medical Education, Warsaw, Poland
  2. National Medical Institute of the Ministry of Interior and Administration in Warsaw, Poland, Pathomorphology Department, Warsaw, Poland
  3. Division of Gynaecological Oncology, Department of Gynaecology, Poznan University of Medical Sciences, Poznan, Poland, 33 Polna St, 60-535 Poznań, Poland

open access

Vol 95, No 4 (2024)
ORIGINAL PAPERS Gynecology
Published online: 2023-10-23

Abstract

Objectives: The aim of the study was to evaluate the B7–H4 expression in endometrial cancer cells and to investigate its relationship with patient prognosis and clinicopathological features of the disease. Material and methods: We performed a single-center, retrospective cohort study that included endometrial cancer patients treated between 2012 and 2019. B7–H4 expression in specimens obtained from 63 patients was examined by immunohistochemical staining. The evaluation of B7H4 immunoreactivity was assessed using Immunoreactivity Scoring (IRS) system. Results: B7–H4 reactivity was observed in all, except one, endometrial cancer patients (98%). Staining intensity: no reaction in one case, weak in 16 (24%) patients, moderate in 25 (37%), and strong in 22 (35%). Twenty-nine (46%) patients showed B7–H4 immunoreactivity in more than 60% of cells, while, in 18 (29%) cases and 16 (25%) patients, the percentages were 30–60% and < 30% respectively. Median IRS was 2 (range 0–6). We found a significantly worse overall survival (OS) rate for patients with high versus low B7–H4 IRS (p = 0.03), however, in multivariate analysis, the difference in patient survival was close to the significance level (p = 0.052). B7–H4 expression was not related to histopathological type of the tumor, tumor grade, lymph node metastases, or the FIGO stage of the disease. Conclusions: Our result suggests that B7–H4 expression might be a useful prognostic factor in endometrial cancer.

Abstract

Objectives: The aim of the study was to evaluate the B7–H4 expression in endometrial cancer cells and to investigate its relationship with patient prognosis and clinicopathological features of the disease. Material and methods: We performed a single-center, retrospective cohort study that included endometrial cancer patients treated between 2012 and 2019. B7–H4 expression in specimens obtained from 63 patients was examined by immunohistochemical staining. The evaluation of B7H4 immunoreactivity was assessed using Immunoreactivity Scoring (IRS) system. Results: B7–H4 reactivity was observed in all, except one, endometrial cancer patients (98%). Staining intensity: no reaction in one case, weak in 16 (24%) patients, moderate in 25 (37%), and strong in 22 (35%). Twenty-nine (46%) patients showed B7–H4 immunoreactivity in more than 60% of cells, while, in 18 (29%) cases and 16 (25%) patients, the percentages were 30–60% and < 30% respectively. Median IRS was 2 (range 0–6). We found a significantly worse overall survival (OS) rate for patients with high versus low B7–H4 IRS (p = 0.03), however, in multivariate analysis, the difference in patient survival was close to the significance level (p = 0.052). B7–H4 expression was not related to histopathological type of the tumor, tumor grade, lymph node metastases, or the FIGO stage of the disease. Conclusions: Our result suggests that B7–H4 expression might be a useful prognostic factor in endometrial cancer.

Get Citation

Keywords

B7–H4; endometrial cancer; IRS; overall survival; immunohistochemistry

About this article
Title

Expression of B7–H4 in endometrial cancer and its impact on patients’ prognosis

Journal

Ginekologia Polska

Issue

Vol 95, No 4 (2024)

Article type

Research paper

Pages

252-258

Published online

2023-10-23

Page views

436

Article views/downloads

310

DOI

10.5603/gpl.96605

Pubmed

37873922

Bibliographic record

Ginekol Pol 2024;95(4):252-258.

Keywords

B7–H4
endometrial cancer
IRS
overall survival
immunohistochemistry

Authors

Katarzyna Gorzelnik
Anna Wasaznik-Jedras
Lukasz Wicherek
Sebastian Szubert

References (35)
  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(3): 209–249.
  2. Kandoth C, Schultz N, Cherniack AD, et al. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013; 497(7447): 67–73.
  3. Concin N, Matias-Guiu X, Vergote I, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer. 2021; 31(1): 12–39.
  4. Raffone A, Travaglino A, Mascolo M, et al. TCGA molecular groups of endometrial cancer: Pooled data about prognosis. Gynecol Oncol. 2019; 155(2): 374–383.
  5. Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res. 2015; 21(4): 687–692.
  6. Zang X, Loke P, Kim J, et al. B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci U S A. 2003; 100(18): 10388–10392.
  7. Sica GL, Choi InH, Zhu G, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 2003; 18(6): 849–861.
  8. Wang JY, Wang WP. B7-H4, a promising target for immunotherapy. Cell Immunol. 2020; 347: 104008.
  9. Vanderstraeten A, Tuyaerts S, Amant F. The immune system in the normal endometrium and implications for endometrial cancer development. J Reprod Immunol. 2015; 109: 7–16.
  10. Kondratiev S, Sabo E, Yakirevich E, et al. Intratumoral CD8+ T lymphocytes as a prognostic factor of survival in endometrial carcinoma. Clin Cancer Res. 2004; 10(13): 4450–4456.
  11. Yan X, Hong Bo, Feng J, et al. B7-H4 is a potential diagnostic and prognostic biomarker in colorectal cancer and correlates with the epithelial-mesenchymal transition. BMC Cancer. 2022; 22(1): 1053.
  12. Wang L, Yang C, Liu XB, et al. B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer. Cancer Cell Int. 2018; 18: 100.
  13. Xie N, Cai JB, Zhang Lu, et al. Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma. Cell Death Dis. 2017; 8(12): 3205.
  14. Dong Q, Ma X. B7-H4 expression is associated with tumor progression and prognosis in patients with osteosarcoma. Biomed Res Int. 2015; 2015: 156432.
  15. Liu W, Shibata K, Koya Y, et al. B7-H4 overexpression correlates with a poor prognosis for cervical cancer patients. Mol Clin Oncol. 2014; 2(2): 219–225.
  16. Tringler B, Zhuo S, Pilkington G, et al. B7-h4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res. 2005; 11(5): 1842–1848.
  17. Simon I, Zhuo S, Corral L, et al. B7-H4 is a novel membrane-bound protein and a candidate serum and tissue biomarker for ovarian cancer. Cancer Res. 2006; 66(3): 1570–1575.
  18. Miyatake T, Tringler B, Liu W, et al. B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration. Gynecol Oncol. 2007; 106(1): 119–127.
  19. Qian Y, Shen L, Cheng L, et al. B7-H4 expression in various tumors determined using a novel developed monoclonal antibody. Clin Exp Med. 2011; 11(3): 163–170.
  20. Liu J, Liu Y, Wang W, et al. Expression of immune checkpoint molecules in endometrial carcinoma. Exp Ther Med. 2015; 10(5): 1947–1952.
  21. Vanderstraeten A, Luyten C, Verbist G, et al. Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy. Cancer Immunol Immunother. 2014; 63(6): 545–557.
  22. Bregar A, Deshpande A, Grange C, et al. Characterization of immune regulatory molecules B7-H4 and PD-L1 in low and high grade endometrial tumors. Gynecol Oncol. 2017; 145(3): 446–452.
  23. Zong L, Yu S, Mo S, et al. B7-H4 further stratifies patients with endometrial cancer exhibiting a nonspecific molecular profile. Arch Pathol Lab Med. 2023 [Epub ahead of print].
  24. Kryczek I, Zou L, Rodriguez P, et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med. 2006; 203(4): 871–881.
  25. Quandt D, Fiedler E, Boettcher D, et al. B7-h4 expression in human melanoma: its association with patients' survival and antitumor immune response. Clin Cancer Res. 2011; 17(10): 3100–3111.
  26. Cheng L, Jiang J, Gao R, et al. B7-H4 expression promotes tumorigenesis in ovarian cancer. Int J Gynecol Cancer. 2009; 19(9): 1481–1486.
  27. Zhang L, Wu H, Lu D, et al. The costimulatory molecule B7-H4 promote tumor progression and cell proliferation through translocating into nucleus. Oncogene. 2013; 32(46): 5347–5358.
  28. Li ZY, Zhang XH, Chen Yu, et al. Clinical significance of B7-H4 expression in matched non-small cell lung cancer brain metastases and primary tumors. Onco Targets Ther. 2013; 6: 869–875.
  29. Zang X, Thompson RH, Al-Ahmadie HA, et al. B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci U S A. 2007; 104(49): 19458–19463.
  30. Zhu J, Chu BF, Yang YP, et al. B7-H4 expression is associated with cancer progression and predicts patient survival in human thyroid cancer. Asian Pac J Cancer Prev. 2013; 14(5): 3011–3015.
  31. Lee V, Murphy A, Le DT, et al. Mismatch repair deficiency and response to immune checkpoint blockade. Oncologist. 2016; 21(10): 1200–1211.
  32. Cao W, Ma X, Fischer JV, et al. Immunotherapy in endometrial cancer: rationale, practice and perspectives. Biomark Res. 2021; 9(1): 49.
  33. FDA grants regular approval to dostarlimab-gxly for dMMR endometrial cancer | FDA n.d. . https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-dostarlimab-gxly-dmmr-endometrial-cancer (21.06.2023).
  34. FDA approves pembrolizumab for advanced endometrial carcinoma | FDA n.d. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-endometrial-carcinoma (21.06.2023).
  35. Patel SP, Kurzrock R. PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol Cancer Ther. 2015; 14(4): 847–856.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk
tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl