title: 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.
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-221 85, Lund, Sweden. sebastian.lundgren@med.lu.se.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lundgren
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-221 85, Lund, Sweden.
authors.forename: Jonna
authors.initials: J
authors.lastname: Berntsson
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-221 85, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85, Uppsala, Sweden.
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, SE-221 85, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
mesh_terms: D000328:Adult; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D005187:Fallopian Tubes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D053668:Syndecan-1 / Q000378:metabolism
chemical_list: D018951:Antigens, CD20; D007145:Immunoglobulin kappa-Chains; C508241:SDC1 protein, human; D053668:Syndecan-1
keywords: CD138; CD20; Immunoglobulin kappa c; Ovarian cancer; Prognosis; Syndecan-1