Prognostic impact of tumour-associated B cells and plasma cells in epithelial ovarian cancer

Abstract

Background: The critical role of the immune system in controlling cancer progression has become evident and immune modulatory therapy is now approved for clinical use. However, while the majority of studies on the inflammatory tumour microenvironment have focused on the cellular immune response, in particular the prognostic and predictive role of various T cell infiltrates, the role of the humoral immune response in this context has long been overlooked. This study aimed to investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in epithelial ovarian cancer (EOC).

Methods: Immunohistochemical expression of immunoglobulin kappa C (IGKC), CD20 and CD138 was analysed in tissue microarrays with tumours from 154 incident cases of EOC from two pooled prospective population-based cohorts. Subsets of corresponding benign-appearing fallopian tubes (n = 38) and omental metastases (n = 33) were also analysed. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of immune-cell specific IGKC, CD20 and CD138 expression on overall survival and ovarian cancer-specific survival.

Results: High IGKC expression correlated significantly with expression of CD20 (p = 0.001) and CD138 (p = 0.035). Expression of IGKC as well as CD138 was significantly higher in primary tumours than in fallopian tubes (p = 0.004 and p = 0.001, respectively). High CD20 and CD138 expression correlated significantly with high tumour grade (p = 0.032 and p = 0.030, respectively). CD20 and IGKC expression was not prognostic but univariable Cox regression analysis revealed high CD138 expression to correlate with a significantly reduced overall survival (HR = 2.20; 95 % CI 1.34-3.55; p-0.001) as well as ovarian cancer-specific survival (HR = 1.95; 95 % CI 1.28-2.98; p = 0.002). The prognostic impact was independent of established clinical parameters (age, grade, clinical stage) as shown in multivariable analysis (HR = 2.28; 95 % CI 1.39-3.75; p = 0.001).

Conclusions: In conclusion, our results demonstrate that plasma cell infiltration in epithelial ovarian cancer has a significant impact on tumour progression and prognosis. The important role of the humoral immune system merits further study and may be harnessed as immune modulatory strategies in cancer therapy.

Keywords: CD138; CD20; Immunoglobulin kappa c; Ovarian cancer; Prognosis; Syndecan-1.

Fig. 1

Immunohistochemical images of IGKC, CD20 and CD138 staining in fallopian tubes, primary and metastatic epithelial ovarian cancer. Sample images (40X magnification) representing immunohistochemical expression of IGKC (first row), CD138 (second row) and CD20 (third row), described as core score, i.e. a multiplier of intensity (0–3) and fraction of staining; left column representing negative CS, middle column intermediate CS and right column high CS

Fig. 2

Distribution of IGKC, CD20 and CD138 expressions in fallopian tubes, primary tumours and metastases. Box plot visualising the staining distribution of (a) IGKC (b) CD20 and (c) CD138 in fallopian tubes, primary tumours and metastases. CD20 expression is described as core score, i.e. a multiplier of fraction in estimated percentage and intensity (0–2) of staining

Fig. 3

Kaplan-Meier estimates of ovarian cancer specific and overall survival in all patients according to CD138 expression. Kaplan Meier analysis of (a) overall survival and (b) ovarian cancer specific survival in strata of low and high CD138 expression. The categories of staining were determined by classification and regression tree analysis based on the core score (CS), whereby low expression = CS ≤ 2.25 and high expression = CS > 2.25