Stage-specific embryonic antigen-4 is a histological marker reflecting the malignant behavior of prostate cancer

Yuichiro Nakamura,Kojiro Ohba,Akihiro Ito,Tomohiro Matsuo,Takenobu Taima,Sen-Itiroh Hakomori,Tomoaki Hakariya,Yasuyoshi Miyata,Tetsuji Suda,Yohei Shida,Hideki Sakai,Seiichi Saito

doi:10.1007/s10719-019-09882-2

Abstract

Stage-specific embryonic antigen-4 (SSEA-4), a specific marker for pluripotent stem cells, plays an important role in the malignant behavior of several cancers. Here, SSEA-4 expression was evaluated by immunohistochemistry using monoclonal antibody RM1 specific to SSEA-4 in 181 and 117 prostate cancer (PC) specimens obtained by biopsy and radical prostatectomy (RP), respectively. The relationships between SSEA-4 expression in cancer cells or the presence of SSEA-4-positive tumor-infiltrating immune cells (TICs) and clinicopathological parameters were analyzed. SSEA-4 expression in cancer cells was significantly associated with Gleason score, local progression, and lymph node and distant metastasis. In RP specimens, high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs were significant predictors of pT3, i.e., invasion and worse biochemical recurrence (BCR) after RP, respectively, in univariate analysis. In contrast, combination of high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs was an independent predictor for pT3 and BCR in multivariate analysis. Biologically this combination was also independently associated with suppression of apoptosis. Thus, the co-expression of SSEA-4 in cancer cells and TICs may have crucial roles in the malignant aggressiveness and prognosis of PC. Invasive potential and suppression of apoptosis may be linked to SSEA-4 expression.

Highlights

Solid tumors are composed of heterogeneous cell populations with different biological and molecular characteristics
Stage-specific embryonic antigen-4 (SSEA-4) expression was mainly detected in the cytoplasm and a part of the cell membrane in cancer cells, and representative examples of low and high SSEA-4 expression in cancer cells are shown in Fig. 1a, b, respectively
Of the biopsy specimens obtained from the prostate cancer (PC) patients, 57 (31.5%) ones were judged as having high SSEA-4 expression

Summary

Introduction

Solid tumors are composed of heterogeneous cell populations with different biological and molecular characteristics. Cancer stem cells (CSCs) play crucial roles in tumor growth and chemoresistance in various types of malignancies [1, 2]. SSEA-4 expression is positively associated with malignant behavior in breast cancer [6, 7] and glioblastoma [8]. Based on these facts, it is speculated that SSEA-4 expression in cancer cells plays a significant role in the malignant aggressiveness of prostate cancer (PC)

Methods

Results

Conclusion