Midkine and NANOG Have Similar Immunohistochemical Expression Patterns and Contribute Equally to an Adverse Prognosis of Oral Squamous Cell Carcinoma.

Hyun-Min Kim,Si-Jung Jang,Bong-Wook Park,June-Ho Byun,Young-Hoon Kang,Gyu-Jin Rho,Jong-Sil Lee

doi:10.3390/ijms18112339

Abstract

To increase the overall survival rate and obtain a better prognosis for oral squamous cell carcinoma (OSCC) patients, the detection of more effective and reliable tumor prognostic markers is needed. This study is focused on the analysis of correlation between the clinicopathological features of OSCCs and the immunohistochemical (IHC) expression patterns of MIDKINE (MK) and NANOG. Sixty-two primary OSCC patients were selected and their pretreatment biopsy specimens were immunohistochemically analyzed for the MK and NANOG proteins. The IHC expression patterns, clinicopathological features, and overall survival rates were assessed to identify any correlations. MK and NANOG showed significantly similar IHC expression patterns: both demonstrated enhanced expression in histologically high-grade and clinically late-stage OSCCs. Weak or negative expression of MK and NANOG was correlated with negative neck node metastasis. Clinicopathologically, late tumor stage, neck node metastasis, high-grade tumor, and palliative treatment groups showed significantly lower overall survival rates. The enhanced expression of MK and NANOG was associated with lower overall survival rates. In particular, enhanced co-detection of MK and NANOG showed significant correlation with poor prognosis. In conclusion, enhanced IHC expression patterns of MK and NANOG in OSCC patients was significantly associated with lower overall survival rates and unfavorable clinicopathological features. These results demonstrate that analysis of IHC expression patterns of MK and NANOG in pretreatment biopsy specimens during the work-up period can provide a more definitive prognosis prediction for each OSCC patient that can help clinicians to develop a more precise individual treatment modality.

Highlights

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and comprises at least 90% of all oral malignancies [1,2]
We demonstrated that the IHC expression patterns of MK and NANOG are highly similar in pretreatment biopsy specimens of OSCCs, and that both markers were strongly expressed in histopathologically high-grade tumors and clinically late-stage OSCCs
Patients were divided into three groups according to the main treatment modality: surgery-only group (Surg), surgery combined with adjuvant radiotherapy or concurrent chemoradiotherapy group (Surg + RT), and palliative radiotherapy or no treatment group (PaRT)

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and comprises at least 90% of all oral malignancies [1,2]. Because the traditional TNM (tumor, node, metastases) classification system and histological grade are limited in their ability to accurately predict the tumor’s aggressiveness and prognosis, various studies have been performed for the detection of more effective prognostic markers in OSCC patients [1,5,6,7]. Embryonic stem cell (ESC) markers such as NANOG, OCT4, SOX2, and STAT3 showed high expression and played important roles in CSCs of OSCC [4,8,9]. Our previous study showed that increased expression of NANOG and mutant p53 in pretreatment OSCC specimens was significantly associated with clinically late-stage and histologically high-grade tumors, positive neck node metastasis, and poor overall survival rates [7]. Pretreatment analysis of a cancerous biopsy specimen can provide a large amount of information regarding tumor characteristics

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Discussion

Conclusion