open access

Vol 57, No 3 (2019)
ORIGINAL PAPERS
Published online: 2019-08-02
Submitted: 2019-03-18
Accepted: 2019-07-19
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Cytoplasmic and membranous receptor-binding cancer antigens expressed on SiSo cells (RCAS1) immunoreactivity in epithelial ovarian cancer cells represent differing biological function of RCAS1

Sebastian Szubert, Wojciech Jozwicki, Lukasz Wicherek, Krzysztof Koper
DOI: 10.5603/FHC.a2019.0012
·
Pubmed: 31388982
·
Folia Histochem Cytobiol 2019;57(3):116-126.

open access

Vol 57, No 3 (2019)
ORIGINAL PAPERS
Published online: 2019-08-02
Submitted: 2019-03-18
Accepted: 2019-07-19

Abstract

Introduction. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a selective suppressor of the immune response that has been linked to the evasion of immune surveillance by cancer cells. However, the exact prognostic impact of RCAS1 on epithelial ovarian cancer (EOC) has not been fully elucidated. The main aim of our study was to evaluate the influence of RCAS1 immunoreactivity (RCAS1-Ir) in EOC cells and in tumor stroma cells on patient overall survival. We also focused on RCAS1-Ir and the structure of the tumor stroma.

Material and methods. RCAS1-Ir was evaluated by means of immunohistochemistry in 67 patients with EOC. We distinguished cytoplasmic and membranous immunoreactivity patterns.

Results. We found that high cytoplasmic RCAS1-Ir in cancer cells was associated with more than a two-time shortened period of overall survival. Membranous RCAS1-Ir in cancer cells, as well as in tumor stroma macrophages and fibroblasts, did not correlate with patient survival. RCAS1-Ir in the cytoplasm of cancer cells was positively correlated with the degree of tumor stroma infiltration by fibroblasts and macrophages, but not with RCAS1-Ir in these cells. On the other hand, membranous RCAS1-Ir in cancer cells was positively correlated with RCAS1-Ir in fibroblasts and macrophages, but not with their quantity.

Conclusions. Due to their different impacts on patient prognosis and tumor stroma structure, it seems that cytoplasmic and membranous RCAS1-Ir in EOC cells may have different biological functions.

Abstract

Introduction. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a selective suppressor of the immune response that has been linked to the evasion of immune surveillance by cancer cells. However, the exact prognostic impact of RCAS1 on epithelial ovarian cancer (EOC) has not been fully elucidated. The main aim of our study was to evaluate the influence of RCAS1 immunoreactivity (RCAS1-Ir) in EOC cells and in tumor stroma cells on patient overall survival. We also focused on RCAS1-Ir and the structure of the tumor stroma.

Material and methods. RCAS1-Ir was evaluated by means of immunohistochemistry in 67 patients with EOC. We distinguished cytoplasmic and membranous immunoreactivity patterns.

Results. We found that high cytoplasmic RCAS1-Ir in cancer cells was associated with more than a two-time shortened period of overall survival. Membranous RCAS1-Ir in cancer cells, as well as in tumor stroma macrophages and fibroblasts, did not correlate with patient survival. RCAS1-Ir in the cytoplasm of cancer cells was positively correlated with the degree of tumor stroma infiltration by fibroblasts and macrophages, but not with RCAS1-Ir in these cells. On the other hand, membranous RCAS1-Ir in cancer cells was positively correlated with RCAS1-Ir in fibroblasts and macrophages, but not with their quantity.

Conclusions. Due to their different impacts on patient prognosis and tumor stroma structure, it seems that cytoplasmic and membranous RCAS1-Ir in EOC cells may have different biological functions.

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Keywords

RCAS1; receptor-binding cancer antigen expressed on SiSo cells; epithelial ovarian cancer; tumor stroma; tumor microenvironment

About this article
Title

Cytoplasmic and membranous receptor-binding cancer antigens expressed on SiSo cells (RCAS1) immunoreactivity in epithelial ovarian cancer cells represent differing biological function of RCAS1

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 57, No 3 (2019)

Pages

116-126

Published online

2019-08-02

DOI

10.5603/FHC.a2019.0012

Pubmed

31388982

Bibliographic record

Folia Histochem Cytobiol 2019;57(3):116-126.

Keywords

RCAS1
receptor-binding cancer antigen expressed on SiSo cells
epithelial ovarian cancer
tumor stroma
tumor microenvironment

Authors

Sebastian Szubert
Wojciech Jozwicki
Lukasz Wicherek
Krzysztof Koper

References (32)
  1. Torre LA, Trabert B, DeSantis CE, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018; 68(4): 284–296.
  2. Chang LC, Huang CF, Lai MS, et al. Prognostic factors in epithelial ovarian cancer: A population-based study. PLoS One. 2018; 13(3): e0194993.
  3. Bois Adu, Reuss A, Pujade-Lauraine E, et al. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials. Cancer. 2009; 115(6): 1234–1244.
  4. Szymankiewicz M, Dziobek K, Sznajdorwska M, et al. An analysis of the influence of infection on overall survival rates, following modified posterior pelvic exenteration for advanced ovarian cancer. Ginekol Pol. 2018; 89(11): 618–626.
  5. Szubert S, Szpurek D, Moszynski R, et al. Extracellular matrix metalloproteinase inducer (EMMPRIN) expression correlates positively with active angiogenesis and negatively with basic fibroblast growth factor expression in epithelial ovarian cancer. J Cancer Res Clin Oncol. 2014; 140(3): 361–369.
  6. Czekierdowski A, Stachowicz N, Czekierdowska S, et al. Prognostic significance of TEM7 and nestin expression in women with advanced high grade serous ovarian cancer. Ginekol Pol. 2018; 89(3): 135–141.
  7. Chen Y, Zhang L, Liu W, et al. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer. Biomed Res Int. 2015; 2015: 589301.
  8. Sonoda K, Nakashima M, Kaku T, et al. A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas. Cancer. 1996; 77(8): 1501–1509.
  9. Sonoda K, Miyamoto S, Hirakawa T, et al. Clinical significance of RCAS1 as a biomarker of uterine cancer. Gynecol Oncol. 2006; 103(3): 924–931.
  10. Nishinakagawa T, Fujii S, Nozaki T, et al. Analysis of cell cycle arrest and apoptosis induced by RCAS1. Int J Mol Med. 2010; 25(5): 717–722.
  11. Sonoda K, Miyamoto S, Nakashima M, et al. The biological role of the unique molecule RCAS1: a bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis. Front Biosci. 2008; 13: 1106–1116.
  12. Galazka K, Opławski M, Windorbska W, et al. The immunohistochemical analysis of antigens such as RCAS1 and B7H4 in the cervical cancer nest and within the fibroblasts and macrophages infiltrating the cancer microenvironment. Am J Reprod Immunol. 2012; 68(1): 85–93.
  13. Sonoda K, Miyamoto S, Hirakawa T, et al. Association between RCAS1 expression and microenvironmental immune cell death in uterine cervical cancer. Gynecol Oncol. 2005; 97(3): 772–779.
  14. Sonoda K, Miyamoto S, Yamazaki A, et al. Biologic significance of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a pivotal regulator of tumor growth through angiogenesis in human uterine cancer. Cancer. 2007; 110(9): 1979–1990.
  15. Sonoda K, Miyamoto S, Hirakawa T, et al. Invasive potency related to RCAS1 expression in uterine cervical cancer. Gynecol Oncol. 2005; 99(1): 189–198.
  16. Sonoda K, Miyamoto S, Kobayashi H, et al. The level of RCAS1 expression is inversely correlated with the number of vimentin-positive stromal cells in epithelial ovarian cancer. Int J Gynecol Cancer. 2009; 19(5): 838–843.
  17. Szubert S, Koper K, Dutsch-Wicherek MM, et al. High tumor cell vimentin expression indicates prolonged survival in patients with ovarian malignant tumors. Ginekol Pol. 2019; 90(1): 11–19.
  18. Sonoda K, Miyamoto S, Hirakawa T, et al. Association between RCAS1 expression and clinical outcome in uterine endometrial cancer. Br J Cancer. 2003; 89(3): 546–551.
  19. Jóźwicki W, Brożyna AA, Siekiera J, et al. Expression of RCAS1 correlates with urothelial bladder cancer malignancy. Int J Mol Sci. 2015; 16(2): 3783–3803.
  20. Szubert S, Koper K, Dutsch-Wicherek MM, et al. The potential predictive value of serum srCaS1 levels for overall survival in endometrial cancer. Ginekol Pol. 2019; 90(3): 134–140.
  21. Jozwicki W, Domaniewski J, Skok Z, et al. Usefulness of histologic homogeneity estimation of muscle-invasive urinary bladder cancer in an individual prognosis: a mapping study. Urology. 2005; 66(5): 1122–1126.
  22. Nakamura Y, Yamazaki K, Oizumi S, et al. Expression of RCAS1 in human gastric carcinoma: a potential mechanism of immune escape. Cancer Sci. 2004; 95(3): 260–265.
  23. Akahira JI, Aoki M, Suzuki T, et al. Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer. Br J Cancer. 2004; 90(11): 2197–2202.
  24. Ali-Fehmi R, Chatterjee M, Ionan A, et al. Analysis of the expression of human tumor antigens in ovarian cancer tissues. Cancer Biomark. 2010; 6(1): 33–48.
  25. Wicherek L, Jozwicki W, Windorbska W, et al. Analysis of Treg cell population alterations in the peripheral blood of patients treated surgically for ovarian cancer - a preliminary report. Am J Reprod Immunol. 2011; 66(5): 444–450.
  26. Dutsch-Wicherek M, Tomaszewska R, Lazar A, et al. The association between RCAS1 expression in laryngeal and pharyngeal cancer and its healthy stroma with cancer relapse. BMC Cancer. 2009; 9: 35.
  27. Dutsch-Wicherek M, Lazar A, Tomaszewska R. The Involvement of RCAS1 in Creating a Suppressive Tumor Microenvironment in Patients with Salivary Gland Adenocarcinoma. Cancer Microenviron. 2010; 4(1): 13–21.
  28. Adamek D, Radwańska E, Gajda M. Expression of RCAS1 protein in microglia/macrophages accompanying brain tumours. An immunofluorescence study. Folia Neuropathol. 2009; 47(3): 240–246.
  29. Jozwicki W, Windorbska W, Brozyna AA, et al. The analysis of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) immunoreactivity within the microenvironment of the ovarian cancer lesion relative to the applied therapeutic strategy. Cell Tissue Res. 2011; 345(3): 405–414.
  30. Ikeda K, Sato M, Tsutsumi O, et al. Promoter analysis and chromosomal mapping of human EBAG9 gene. Biochem Biophys Res Commun. 2000; 273(2): 654–660.
  31. Biedka M, Nowikiewicz T, Dziobek K, et al. The analysis of Treg lymphocytes in the blood of patients with breast cancer during the combined oncological treatment. Breast J. 2019; 26(1).
  32. Shih IM, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004; 164(5): 1511–1518.

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