Loss of Single-Stranded DNA Binding Protein 2 Expression Is Associated with Aggressiveness and Poor Overall Survival in Patients with Invasive Breast Carcinoma

Abstract

Background: Single-stranded DNA binding protein 2 (SSBP2) is involved in the DNA damage response and the maintenance of genome stability. Previous studies have suggested that SSBP2 has a tumor suppressor function or oncogenic function. Loss of SSBP2 expression has been reported in various tumors. However, the role of SSBP2 expression in invasive breast carcinoma has not been reported. Methods: Immunohistochemical staining for SSBP2 was performed on tissue microarrays consisting of 491 invasive breast carcinoma cases. The result of nuclear SSBP2 staining was stratified as either negative or positive. Then, we investigated the correlations between SSBP2 expression and various clinicopathological parameters and patient outcomes. Results: Loss of nuclear SSBP2 expression was observed in 61 cases (12.4%) of 491 invasive breast carcinomas. Loss of nuclear SSBP2 expression was significantly correlated with larger tumor size (p < 0.001, chi-squared test), higher histological grade (p = 0.016, Cochran–Armitage trend test), higher pathological T stage (p < 0.001, Cochran–Armitage trend test), estrogen receptor status (p < 0.001, chi-squared test), and molecular subtype (p < 0.001, chi-squared test). Kaplan–Meier survival analysis revealed that patients with loss of nuclear SSBP2 expression had worse overall survival (p = 0.013, log-rank test). However, loss of nuclear SSBP2 expression was not correlated with recurrence-free survival (p = 0.175, log-rank test). Conclusions: Loss of nuclear SSBP2 expression was associated with adverse clinicopathological characteristics and poor patient outcomes. SSBP2 acts as a tumor suppressor in invasive breast carcinoma and may be used as a prognostic biomarker.

Immunohistochemical Analysis of Single-Stranded DNA Binding Protein 2 in Non-Melanoma Skin Cancers

“…SSBP2-null mice showed an enhanced predisposition to malignancy [7], and SSBP2 was downregulated in prostate cancer and esophageal squamous cell carcinoma cell lines and inhibited tumor cell growth [8,9]. Low SSBP2 expression at the protein level has been linked to an aggressive phenotype and unfavorable prognosis in some types of solid tumors [10][11][12][13]. However, studies on glioblastoma with an SSBP2-inherited variant [14] and hepatocellular carcinoma [15] showed that high SSBP2 expression was associated with poor clinical outcomes, suggesting an oncogenic role of SSBP2.…”