Immunoglobulin Kappa C Predicts Overall Survival in Node-Negative Breast Cancer

Background: Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzedthe association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients.Material and Methods: IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status.Results: 160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantlyassociated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360–0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233–0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315–0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196–0.705).Conclusion: Expression of IGKC has an independent protective impact on DFS and OS in node-negative breast cancer

Clinicopathological characteristics of all patients (n = 335).

<p>HER-2 human epidermal growth factor receptor 2.</p

In ER negative carcinomas (n = 64), high IGKC expression had a significant association with longer DFS (Log-rank test: P = 0.044; Fig. 3A) and longer OS (Log-rank test: P = 0.044; Fig. 3B).

<p>(C, D) In ER positive carcinomas (n = 271), Kaplan Meier survival analysis showed that there was no significant association between IGKC and DFS (Log-rank test: P = 0.088; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044741#pone-0044741-g003" target="_blank">Fig.3C</a>), and OS had a borderline association with IGKC (Log-rank test: P = 0.050; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044741#pone-0044741-g003" target="_blank">Fig.3D</a>).</p

Cox regression analysis of IGKC expression for disease-free survival (DFS) in the entire cohort (n = 335).

<p>ER Estrogen receptor; PR Progesterone receptor; HER-2 human epidermal growth factor receptor 2; HR hazard ratio; 95%-CI 95%-confidence interval.</p>a<p>The total number of available cases for Ki-67 expression in univariate Cox regression analysis is 322.</p

Bivariate Cox analysis of IGKC expression with Ki-67 expression for disease-free survival (DFS) (A) and overall survival (OS) (B) (n = 322).

<p>HR hazard ratio; 95%-CI 95%-confidence interval.</p

Association of IGKC expression with prognosis in the entire cohort (n = 335).

<p>Kaplan Meier survival analysis illustrated that high IGKC expression was significantly associated with longer DFS (Log-rank test: P = 0.015; Fig. 2A) and longer OS (Log-rank test: P = 0.009; Fig. 2B). A comparable prognostic influence was seen when IGKC status was used for DFS (Log-rank test: P = 0.006; Fig. 2C) and OS (Log-rank test: P = 0.009; Fig. 2D), respectively.</p

Cox regression analysis of IGKC expression for overall survival (OS) in the entire cohort (n = 335).

<p>ER Estrogen receptor; PR Progesterone receptor; HER-2 human epidermal growth factor receptor 2; HR hazard ratio; 95%-CI 95%-confidence interval.</p>a<p>The total number of available cases for Ki-67 expression in univariate Cox regression analysis is 322.</p

In luminal A carcinomas (n = 224), IGKC had no significant association with DFS (Log-rank test: P = 0.591; Fig. 4A) and OS (Log-rank test: P = 0.183; Fig. 4B).

<p>(C, D) In luminal B carcinomas (n = 55), Kaplan-Meier curves illustrated that high IGKC expression had significantly longer DFS than low IGKC expression (Log-rank test: P = 0.009; Fig. 4C). Moreover, OS also showed a borderline association with IGKC (Log-rank test: P = 0.057; Fig. 4D).</p

Correlation of IGKC expression with clinicopathological characteristics (n = 335).

*<p>Correlation between variables was determined by Chi-Quare test.</p><p>HER-2 human epidermal growth factor receptor 2.</p>a<p>The total number of available cases for Ki-67 expression is 322.</p