Scientific publications

Prognostic markers of inflammation in endometrioid and clear cell ovarian cancer

Aug 1, 2022 | Magazine: International Journal of Gynecological Cancer

Alejandro Gallego  1 , Marta Mendiola  2   3 , Barbara Hernando  4 , Alberto Berjon  2   5 , Alice Cadiz  4 , Blas Chaves-Urbano  4 , Victoria Heredia-Soto  6 , Emanuela Spagnolo  7 , Alicia Hernández Gutiérrez  7   8 , David Hardisson  2   3   5   8 , Geoff Macintyre  4 , Andres Redondo  9   10 , Maria Jose Garcia  11

Objectives: Cancer-related systemic inflammation has been associated with prognosis in multiple cancer types. Conversely, local inflammation, which is characterized by dense intratumoral immune infiltrates, is a favorable predictor of survival outcome. However, these survival associations are not well established in ovarian cancer, particularly in the less frequent endometrioid and clear cell endometriosis associated histotypes.

Methods: This retrospective study included 119 patients (63 endometrioid and 56 clear cell ovarian carcinomas). We performed a comprehensive survival association analysis of both systemic (neutrophil-to-lymphocyte ratio or presence of endometriosis) and local inflammation markers (CD3+ and CD8+ tumor infiltrating lymphocytes) using multivariate Cox proportional hazards models that account for confounding factors.

Results: Medium to high levels of intraepithelial CD8+ tumor infiltrating lymphocytes are associated with longer survival in endometrioid ovarian cancer (p=0.04). In addition, we found that intraepithelial CD8+ tumor infiltrating lymphocytes are prognostic in clear cell ovarian cancer (p=0.02), and that intraepithelial CD3+ tumor infiltrating lymphocytes are also associated with improved outcome (p=0.02). Furthermore, intratumoral CD3+ and CD8+ tumor infiltrating lymphocytes showed improved prognosis in the endometrioid subtype (p<0.1). No prognostic value was observed for systemic immune markers.

Conclusions: In this study, patients with endometrioid and clear cell ovarian cancer with moderate to high CD8+ and CD3+ intraepithelial tumor infiltrating lymphocytes had longer overall survival. Higher expression of intratumoral CD3+ and CD8+ tumor infiltrating lymphocytes also showed an improved outcome in endometrioid ovarian cancer. In contrast, systemic inflammation, evaluated by neutrophil-to-lymphocyte ratio or presence of endometriosis, did not have a prognostic impact in these histologic subtypes.

CITATION  Int J Gynecol Cancer. 2022 Aug 1;32(8):1009-1016.  doi: 10.1136/ijgc-2022-003353