Cyclooxygenase-2 expression as a prognostic factor in pediatric classical Hodgkin lymphoma

Clin Transl Oncol. 2020 Sep;22(9):1539-1547. doi: 10.1007/s12094-020-02297-8. Epub 2020 Jan 22.

Abstract

Purpose: Cyclooxygenase-2 (COX-2) is an inflammation-related enzyme that has been shown to have a role in tumor initiation, angiogenesis, and proliferation. It has been demonstrated that COX-2 expression is increased in many tumors and is a negative prognostic parameter. Our objective is to investigate the prognostic value of COX-2 expression in pediatric patients with classical Hodgkin lymphoma (CHL).

Methods: This was a retrospective analysis in pediatric patients (n = 127) diagnosed with CHL and treated at the pediatric oncology department, National Cancer Institute, Cairo University, January 2005-June 2013. We correlated COX-2 immunostaining in Reed-Sternberg (RS) cells with clinical variables and outcome.

Results: COX-2 was expressed on 38.6% of RS cells. The median follow-up time was 48.4 months (range 4-114 months). The 5-year OS and PFS, in COX-2(+ve) versus COX-2(-ve) was 85.3% versus 96.0% (p = 0.248) and 78.6% versus 84.3% (p = 0.354), respectively. A multivariate analysis showed that COX-2(+ve) was not significantly associated with the 5-year OS (HR = 2.9; 95% CI 0.7-12.4, p = 0.149) or with the 5-year PFS (HR = 1.4; 95% CI 0.6-3.2, p = 0.490). High-risk patients in the COX-2(+ve) group had a significantly lower 5-year OS (p = 0.021). The 5-year PFS was significantly lower in the COX-2(+ve) group with B symptoms (p = 0.023) and bulky disease (p = 0.028). Radiotherapy was given only to high-risk patients; survival was much better in radiation-treated children in both the Cox-2(+ve) and Cox-2(-ve) groups. The magnitude of the radiotherapy effect was also greater in the Cox-2(+ve) group, but this difference was not statistically significant.

Conclusion: COX-2 expression showed a tendency to be a poor prognostic factor, but it failed to provide meaningful independent information. Further larger studies are needed to investigate COX-2 as a prognostic factor and potential therapeutic target.

Keywords: COX-2; Classical Hodgkin lymphoma; Pediatric; Prognostic factor; Radiotherapy.

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / metabolism
  • Child
  • Child, Preschool
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / metabolism
  • Female
  • Follow-Up Studies
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / enzymology*
  • Hodgkin Disease / pathology
  • Hodgkin Disease / radiotherapy
  • Humans
  • Male
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Cyclooxygenase 2
  • PTGS2 protein, human