Cytoplasmic Expression of P16 is Related to Low Infiltration of CD8+ T cell and Poor Prognosis in Digestive Neuroendocrine Carcinoma

Ling-Jun Song^1#, Xue-Mei Zhang^1#, Ting Wang^2#, Lin Yuan¹, Hao Yue¹, Guo-Hui Fu^1* and Wei-Wei Shen^1*

¹Pathology Center, Shanghai General Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, P.R. China

²Department of Pathology, Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China

^#These authors contributed equally to this work

*Corresponding Author : Wei-Wei Shen, MD, PhD
Pathology Center, Shanghai General Hospital/Faculty of Basic Medicine, Shanghai, P. R. China
Tel: 86-21- 63846590-776601
E-mail: weiweishen@126.com

Guo-Hui Fu, MD, PhD
Pathology Center, Shanghai General Hospital/Faculty of Basic Medicine, Shanghai, P. R. China
Tel: 86-21-63846590-776601
E-mail: fuguhu@263.net

Received: December 18, 2017 Accepted: December 18, 2017 Published: January 12, 2018

Citation: Ling-Jun S, Xue-Mei Z, Wang T, Yuan L, Yue H, et al. (2018) Cytoplasmic Expression of P16 is Related to Low Infiltration of CD8+ T cell and Poor Prognosis in Digestive Neuroendocrine Carcinoma. J Diagn Tech Biomed Anal 7:1.

Background and Aims: The aim of this study is to examine the predictive and prognostic value of cytoplasmic P16Ink4A (cP16) and poor infiltration of CD8+ T cell in primary digestive neuroendocrine carcinoma (dNEC). Methods: We retrospectively reviewed 86 cases of NEC and mixed NEC (all cases thereafter refer to NEC), which had primary sites in digestive system. Kaplan-Meier survival curves and log-rank test were used for the survival analysis. Bioinformatics analysis was performed to identify the P16-related pathways. Results: The expression frequency of P16 in dNEC and adjacent tissues was 81.4% and 19.3% respectively (p<0.0001). There was no difference in overall survival (OS) between dNEC patients with P16 positive or negative expression. However, there was a statistically lower OS in dNEC patients with cP16 expression than those without cP16 expression (p=0.050). In addition, cP16 expression was correlated with poor infiltration of intratumoral CD8+ T cells. Furthermore,we found that dNEC patients with two features of cP16 expression in tumor and poor infiltration of CD8+ T cells in intratumoral tissue showed more poor survival (p=0.0133) than patients with single feature alone respectively. Bioinformatics analysis suggested that EGR1 and HLA class I might be involved in the inhibitory effect of cP16 on intratumoral infiltrated T cells. Conclusions: Therefore, the cP16 and poor intratumoral infiltration of CD8+ T cells may serve as poor prognostic biomarkers in dNEC. CP16 expression is associated with decreased intratumoral infiltration of CD8+ T cells probably related to deregulation of EGR1/ HLA class I pathway.