Impact of Activation of EGFL7 within Microenvironment of High Grade Ovarian Serous Carcinoma on Infiltration of CD4+ and CD8+ Lymphocytes

Medicina (Kaunas). 2022 Apr 24;58(5):588. doi: 10.3390/medicina58050588.

Abstract

Background: It has been demonstrated that Egfl7 promotes tumor cell escape from immunity by downregulating the activation of tumor blood vessels. Aim: to analyze mRNA expression of EGFL7 within the tumor microenvironment of high-grade ovarian serous carcinoma and its association with a number of intraepithelial CD4+/CD8+ lymphocytes and ICAM-1 expression. Methods: qPCR analysis of EGFL7 mRNA in cancer cells and adjacent stromal endothelium microdissected from formalin-fixed paraffin-embedded tumors of 59 high-grade ovarian serous carcinoma patients, was performed. Infiltration of intraepithelial lymphocytes (CD4+/CD8+) and expression of ICAM-1 were evaluated by immunohistochemistry and compared between tumors with different statuses of EGFL7 expression. Results: EGFL7 was expressed in cancer cells (9/59, 15.25%), endothelium (8/59, 13.56%), or both cancer cells and adjacent endothelium (4/59, 6.78%). ICAM-1 was expressed on cancer cells (47/59, 79.66%), stromal endothelium (46/59, 77.97%), or both epithelium and endothelium (40 of 59, 67.8%). EGFL7-positivity of cancer cells and endothelium was associated with lower intraepithelial inflow of CD4+ (p = 0.022 and p = 0.029, respectively) and CD8+ lymphocytes (p = 0.004 and p = 0.031, respectively) but impact neither epithelial nor endothelial ICAM-1 expression (p = 0.098 and p = 0.119, respectively). The patients' median follow-up was 23.83 months (range 1.07-78.07). Lack of prognostic significance of EGFL7-status and ICAM-1 expression was notified. Conclusion: EGFL7 is activated in the cancer cells as frequently as in the endothelium of human high-grade ovarian serous carcinoma. Activation of EGFL7 in cancer cells and/or endothelial cells could negatively impact diapedesis regardless of localization.

Keywords: CD4+; CD8+; Egfl-7; ICAM-1; diapedesis; ovarian cancer.

MeSH terms

  • CD4-Positive T-Lymphocytes* / metabolism
  • CD4-Positive T-Lymphocytes* / pathology
  • CD8-Positive T-Lymphocytes* / metabolism
  • CD8-Positive T-Lymphocytes* / pathology
  • Calcium-Binding Proteins* / metabolism
  • Cystadenocarcinoma, Serous* / pathology
  • EGF Family of Proteins* / metabolism
  • Endothelial Cells / metabolism
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • RNA, Messenger
  • Tumor Microenvironment

Substances

  • Calcium-Binding Proteins
  • EGF Family of Proteins
  • EGFL7 protein, human
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Intercellular Adhesion Molecule-1