Prognostic value of CA125 in diffuse large B-cell lymphoma

Abstract

Background: Carbohydrate antigen 125 (CA125) is one of the most commonly used tumor biomarker for evaluating the prognosis of solid neoplasms. It has been reported that serum CA125 is correlated with the prognosis of non-Hodgkin's lymphoma. The objective of this study is to explore the clinical value of CA125 in diffuse large B-cell lymphoma (DLBCL).

Methods: We retrospectively analyzed the clinical and pathological data in a cohort of 315 newly diagnosed patients with DLBCL. In our case, the correlations between serum CA125 and clinicopathological parameters were analyzed. Kaplan-Meier survival curve and cox proportional hazards model were applied to evaluate the prognosis. The expression of CA125 in DLBCL paraffin tissues was detected by immunohistochemistry.

Results: 82 patients (26%) with DLBCL had elevated serum CA125 levels at diagnosis. Elevated serum CA125 levels were associated with poor performances status, greater than or equal to 2 Extra-nodal sites, advanced Ann Arbor stage (III-IV), presence of B symptoms, presence of bulky mass, presence of effusion, intermediate/high-risk International Prognostic Index (IPI), elevated lactate dehydrogenase levels and reduced albumin levels. Patients with elevated serum CA125 levels at diagnosis had shorter progression free survival (PFS) and overall survival (OS). Multivariate analysis revealed that serum CA125, cell of origin, IPI score and albumin were independent prognostic factors for OS and PFS. In addition, the results of the immunohistochemistry indicated that none of the 82 DLBCL paraffin tissues expressed CA125 in lymphoma cells and the surrounding microenvironment cells.

Conclusions: Serum CA125 detected at the initial diagnosis is a strong predictor of prognosis in patients with DLBCL.

Keywords: biomarker; carbohydrate antigen 125; diffuse large B-cell lymphoma; overall survival; prognosis; progression free survival.

Figure 1

Correlation between serum carbohydrate antigen 125 (CA125) levels and survival. (A) Overall survival (OS) and (B) Progression-free survival (PFS) of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients by pretreatment serum CA125 levels.

Figure 2

Kaplan-Meier survival curves of patients with DLBCL. OS of different serum CA125 levels in (A) the male group, (B) the female group, (C) the age > 60 group, (D) the age ≤ 60 group, (E) the Eastern Cooperative Oncology Group performance status (ECOG PS) < 2 group, (F) the extra-nodal sites < 2 group, (G) the absence of B symptoms group, (H) the absence of bulky mass group, (I) the absence of effusion group, (J) the lactate dehydrogenase (LDH) > ULN group, (K) the cell of origin (COO) (Han’s) non-germinal center B-cell (non-GCB) group, (L) the Ki-67 ≥ 75% group.

Figure 3

Kaplan-Meier survival curves of patients with DLBCL. PFS of different serum CA125 levels in (A) the male group, (B) the female group, (C) the age > 60 group, (D) the age ≤ 60 group, (E) the ECOG PS < 2 group, (F) the extra-nodal sites ≥ 2 group, (G) the extra-nodal sites < 2 group, (H) the Ann Arbor stage III-IV group, (I) the absence of B symptoms group, (J) the absence of bulky mass group, (K) the absence of effusion group, (L) the International Prognostic Index (IPI) score 3-5 group, (M) the LDH > ULN group, (N) the albumin (ALB) normal group, (O) the COO (Han’s) non-GCB group, (P) the Ki-67 ≥ 75% group.

Figure 4

Immunohistochemistry staining of CA125 in DLBCL tissues. (A) Abdominal DLBCL: CA125 staining were negative in tumor cells and surrounding microenvironment cells (magnification ×20). (B) Parotid gland DLBCL: CA125 staining were negative in tumor cells and surrounding microenvironment cells. Residual duct epithelium cells were positive for internal control (magnification ×20). (C) Nasopharyngeal DLBCL: CA125 staining were negative in tumor cells and surrounding microenvironment cells. Pseudostratified columnar ciliated epithelium cells were positive for internal control (magnification ×20). (D) Ovarian tissue: Positive control of CA125 (magnification ×20).