Abstract
Single-stranded DNA binding protein 2 (SSBP2) is ubiquitously expressed, with several studies reporting it to be a tumor suppressor. We investigated SSBP2 expression and its clinicopathological significance in gastric cancer. SSBP2 expression was examined by immunohistochemistry in 539 gastric cancer sections. The cases were divided into three subtypes, namely, Epstein–Barr virus-associated (EBV), microsatellite unstable, and others (microsatellite stable and EBV negative), based on the molecular classification of The Cancer Genome Atlas (TCGA). Cases were also divided into two subgroups according to the amplification status of human epidermal growth factor receptor 2 (HER2). Most cases showed SSBP2 positivity, and only 24 (4.5%) cases displayed negative nuclear expression. Loss of nuclear expression correlated significantly with high pT category (P = 0.001), nodal metastasis (P = 0.002), and stage of progression (P = 0.005), with no correlation between molecular characteristics and SSBP2 expression. All HER2 amplification cases displayed positive SSBP2 expression. Negative SSBP2 cases showed significantly shorter recurrence-free survival (RFS) compared to positive SSBP2 cases (P = 0.008). Loss of nuclear expression of SSBP2 was significantly associated with shorter RFS in the microsatellite stable and EBV negative groups (P = 0.002), as well as the HER2 negative group (P = 0.007). However, there were no statistically significant differences in multivariate analyses. Loss of nuclear expression of SSBP2 was a poor prognostic factor, associated with stage of progression and recurrence, and showed no significant difference in molecular characteristics, including TCGA subtype and HER2 status.
Highlights
IntroductionGastric cancer is a common malignant tumor of the digestive system and a heterogeneous disease with diverse histopathological characteristics
According to the The Cancer Genome Atlas (TCGA) molecular subtypes of gastric adenocarcinoma, the 539 gastric cancer cases were classified into Epstein–Barr virus (EBV) (35 cases, 6.5%), microsatellite instability (MSI) (44 cases, 8.2%), and ‘others’ (460 cases, 85.3%) subgroups
EBER-ISH positive cases were considered to be of EBV subtype, whereas, cases were classified as MSI when one or more of the four mismatch repair proteins displayed negative results
Summary
Gastric cancer is a common malignant tumor of the digestive system and a heterogeneous disease with diverse histopathological characteristics. The Cancer Genome Atlas (TCGA) research network recently divided the molecular classification of gastric cancer into four subgroups: Epstein–Barr virus (EBV), microsatellite instability (MSI), genomic stability (GS), and chromosomal instability (CIN) associated tumors [5]. In advanced gastric cancers (AGC), the probability of metastasis or peritoneal seeding dissemination is still high with poor overall prognosis [6]. Many studies have been conducted on molecular targeted therapies in addition to conventional chemotherapy [7]
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