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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 7  |  Page : 176-178
 

Programmed cell death 1 expression in esophageal squamous cell carcinoma and association with clinical characteristics


1 Department of Thoracic Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, PR China
2 Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, PR China
3 Henan University Nursing College, Kaifeng City, Henan 475004, PR China

Date of Web Publication20-Jul-2016

Correspondence Address:
L Li
Henan University Nursing College, Kaifeng City, Henan 475004
PR China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.186574

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 » Abstract 

OBJECTIVE: The aim of this retrospective study was to evaluate the programmed cell death 1 (PD-1) expression in esophageal squamous cell carcinoma (ESCC) and association with clinical characteristics. MATERIALS AND METHODS: From January 2009 to December 2014, 88 patients with ESCC were retrospectively included in this study. Eighty-eight cancer tissues, 35 paraneoplastic atypical hyperplasia tissues (PAHTs), and 30 relative normal esophageal tissues (RNETs) were collected and tested for expression of PD-1 by immunohistochemistry assay. The PD-1 expression and clinical characteristics of the ESCC patients were evaluated. The prognosis of the ESCC patients was compared between the PD-1 positive and negative patients. RESULTS: The PD-1 positive rate was 51.2% (45/88), 22.9% (8/35), and 6.7% (2/30) for the cancer tissue, PAHT, and RNET, respectively, with statistical difference (P < 0.05); The PD-1 expression was significantly associated with lymph node metastasis (P < 0.05) and pathology grade (P < 0.05). The median overall survival was 29.8 months and 32.1 months for the PD-1 positive and negative groups without statistical difference (hazard ratio = 1.00, 95% confidence interval = 0.58-1.71, P < 0.05). CONCLUSION: PD-1 may play a key role in the process of carcinogenesis of ESCC but not associated with prognosis and overall survival.


Keywords: Esophageal squamous cell carcinoma, immunohistochemistry assay, prognosis, programmed cell death 1


How to cite this article:
Feng Z, Xiang-lei L, Hai-tao W, Zuo-pei W, Bao-li H, Hai-feng Z, Xiao-long W, Li L. Programmed cell death 1 expression in esophageal squamous cell carcinoma and association with clinical characteristics. Indian J Cancer 2015;52, Suppl S3:176-8

How to cite this URL:
Feng Z, Xiang-lei L, Hai-tao W, Zuo-pei W, Bao-li H, Hai-feng Z, Xiao-long W, Li L. Programmed cell death 1 expression in esophageal squamous cell carcinoma and association with clinical characteristics. Indian J Cancer [serial online] 2015 [cited 2018 Dec 15];52, Suppl S3:176-8. Available from: http://www.indianjcancer.com/text.asp?2015/52/7/176/186574

Feng Z and Xiang-lei Li contributed equally to this work



 » Introduction Top


Esophageal cancer is one of the leading causes of cancer-related death worldwide, especially in China. It was reported about 38,780 new cases of esophageal cancer and 25,610 death were found in the United States in the year 2012. [1] Although the esophageal cancer mortality rates have decreased somewhat over the past three decades with the improvement of its socioeconomic status and lifestyle according to the data from China, the exact mechanism for esophageal was not clear. [2] Programmed cell death protein 1 (PD-1), also known as PD-1 and cluster of differentiation 279 (CD279), is a protein that, in humans, is encoded by the PDCD1 gene. PD-1, functioning as an immune checkpoint, plays an important role in downregulating the immune system by preventing the activation of T-cells, which in-turn reduces autoimmunity and promotes self-tolerance. [3],[4],[5] Some articles have reported the PD-1 expression pattern in esophageal cancer, but the results were not conclusive. [6],[7],[8]


 » Materials and Methods Top


Patients included in this study

From January 2009 to December 2014, 88 patients with esophageal squamous cell carcinoma (ESCC) were retrospectively included in this study. Eighty-eight cancer tissues, 35 paraneoplastic atypical hyperplasia tissues (PAHTs), and 30 relative normal esophageal tissues (RNETs) were collected and tested for expression of PD-1 by immunohistochemistry assay. For the included 88 patients, 61 cases were male and 27 subjects were female, with the mean age of 69.4 ± 8.2 years old. The detailed characteristics of the included 88 patients are demonstrated in [Table 1].
Table 1: The general characteristics of the included 88 subjects


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Immunohistochemistry assay

We obtained 88 ESCC cancer tissues, 35 PAHTs, and 30 RNETs from patients who underwent surgery at Department of Thoracic Surgery of Huaihe Hospital of Henan University. Written informed consent was obtained from all patients in our study. Tissues were fixed, processed by conventional paraffin-embedded method, and then sectioned (5 mm thick) continuously. Hematoxylin and eosin staining was performed to verify the tissue lesions. For PD-A antibody staining, antigen retrieval was done by high-pressure heating followed by the incubation with 5% block serum for 30 min. Sections were incubated with primary antibody at 4°C overnight. After washed for three times, the sections were incubated for 30 min with goat anti-rabbit secondary IgG and detected by incubation with SP complex. The tissue sections were finally stained with hematoxylin for a short period and subsequently detected under a microscope.

Statistical analysis

All the data were analyzed by STATA11.0 software (Stata Corporation, College Station, TX, USA). The Chi-square test was used to test the association between PD-1 expression and clinical characteristics. The overall survival compared between PD-1 positive and negative groups was tested by log-rank test. A two-tailed P < 0.05 was considered statistically significant.


 » Results Top


Programmed cell death 1 expression

PD-1 positive rate was 51.2% (45/88), 22.9% (8/35), and 6.7% (2/30) for the cancer tissue, PAHT, and RNET, respectively, with statistical difference (P < 0.05). The positive rate in cancer tissue was much higher than those of PAHT and RNET with significant difference (P < 0.05).

The association between programmed cell death 1 expression and clinical characteristics

PD-1 expression was significantly associated with lymph node metastasis (P < 0.05) and pathology grade (P < 0.05). Moreover, no significant association between its expression and age (P > 0.05), gender (P > 0.05), tumor-node-metastasis stage (P > 0.05), depth of tumor invasion (P > 0.0), and tumor diameter (P > 0.5) was found [Table 2].
Table 2: The association between programmed cell death 1 expression and clinical characteristics


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Programmed cell death 1 expression and prognosis

The median overall survival was 29.8 months and 32.1 months for the PD-1 positive and negative groups without statistical difference (hazard ratio = 1.00, 95% confidence interval = 0.58-1.71, P < 0.05) [Figure 1].
Figure 1: The overall survival curve of the programmed cell death 1 positive and negative groups

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 » Discussion Top


Global cancer statistics indicated that esophageal cancer was the sixth leading cause of cancer-related death worldwide and one of most difficult gastrointestinal tumors to treat and cure. [9],[10] Remote metastasis can be found in more than half of patients at the time of the diagnosis. Surgery is the standard treatment procedure for localized and resectable esophageal cancer. [11] However, the prognosis was relatively poor with overall 5-year survival of 25-40% after surgery. [12],[13] Thereafter, to improve patients' prognosis, novel strategies need to be developed and established. [14]

PD-1 is a cell surface receptor that belongs to the immunoglobulin superfamily and is expressed on T-cells and pro-B cells; [3] PD-1 binds two ligands, PD-ligand-1 (L1) and PD-L2. The inhibitory effect of PD-1 is accomplished through a dual mechanism of promoting apoptosis (PD) in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T-cells (suppressor T-cells). Ohigashi et al. [4],[14] discuss the clinical significance of PD-L1 and PD-L2 expressions in human esophageal cancer. In their study, they found that PD-L1 positive patients had a significantly poorer prognosis than the negative patients. This was more pronounced in the advanced stage of tumor than in the early stage. Furthermore, multivariate analysis indicated that PD-L status was an independent prognostic factor. Moreover, they believe that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targetingPD-1/PD-L pathway. In the present study, we found that the positive rate of PD-1 in cancer tissue was much higher than those of PAHT and RNET with significant difference (P < 0.05) which indicated that PD-1 may play a key role in the process of carcinogenesis of ESCC. However, in this study, we did not find the overall survival difference between the PD-1 positive and negative groups, which was not in accordance with Ohigashi's study. A small number of cases may lead to the negative results for the association between PD-1 expression and overall survival.

Financial support and sponsorship

This study is supported by Science and Technology Department Fund Project (No. 152300410066).

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 1
    
2.
Chen W, He Y, Zheng R, Zhang S, Zeng H, Zou X, et al. Esophageal cancer incidence and mortality in China, 2009. J Thorac Dis 2013;5:19-26.  Back to cited text no. 2
    
3.
Momtaz P, Postow MA. Immunologic checkpoints in cancer therapy: Focus on the programmed death-1 (PD-1) receptor pathway. Pharmgenomics Pers Med 2014;7:357-65.  Back to cited text no. 3
    
4.
Hawkes EA, Grigg A, Chong G. Programmed cell death-1 inhibition in lymphoma. Lancet Oncol 2015;16:e234-45.  Back to cited text no. 4
    
5.
Hamid O. Immunotherapy for melanoma using programmed death 1 checkpoint inhibitors. Clin Adv Hematol Oncol 2014;12:782-4.  Back to cited text no. 5
    
6.
Eto S, Yoshikawa K, Nishi M, Higashijima J, Tokunaga T, Nakao T, et al. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer 2016;19:466-71.  Back to cited text no. 6
    
7.
Kerr KM, Tsao MS, Nicholson AG, Yatabe Y, Wistuba II, Hirsch FR; IASLC Pathology Committee. Programmed death-ligand 1 immunohistochemistry in lung cancer: In what state is this art? J Thorac Oncol 2015;10:985-9.  Back to cited text no. 7
[PUBMED]    
8.
Yamane H, Isozaki H, Takeyama M, Ochi N, Kudo K, Honda Y, et al. Programmed cell death protein 1 and programmed death-ligand 1 are expressed on the surface of some small-cell lung cancer lines. Am J Cancer Res 2015;5:1553-7.  Back to cited text no. 8
    
9.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58:71-96.  Back to cited text no. 9
    
10.
Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med 2003;349:2241-52.  Back to cited text no. 10
    
11.
Knisely JP, Burtness BA, Salem RR. Surgical treatment of esophageal cancer. N Engl J Med 2003;348:1177-9.  Back to cited text no. 11
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12.
Argyres MI. Esophageal cancer. N Engl J Med 2004;350:1363-4.  Back to cited text no. 12
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13.
Scherübl H, Zeitz M. Esophageal cancer. N Engl J Med 2004;350:1363-4.  Back to cited text no. 13
    
14.
Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 2005;11:2947-53.  Back to cited text no. 14
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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