Targets for molecular therapy in esophageal squamous cell carcinoma: an immunohistochemical analysis

Abstract Background Tumor associated macrophages and tumor infiltrating lymphocytes contribute significantly to the development of immunosuppressive properties of tumor. In this study we performed immunohistochemical analysis of immune cells of esophageal tumors stroma. Methods Paraffin‑embedded tissue specimens from 48 esophageal squamous cell carcinoma patients were retrospectively collected for immunohistochemical analysis of stromal cells. For staining of macrophages, CD68, CD163, CD206, PU.1 and iNOS were used. For T-cells detection CD8, CD3, FOXP3 were used. As well we performed staining for PD-L1 that can be expressed on tumor associated macrophagesand tumor cells. Clinicopathological and survival data were collected and analyzed using the χ2 and Fisher exact tests, Kaplan–Meier curves, and the log‑rank test. The correlation analysis was performed with Spearman correlation coefficient. Results The level of CD206 expression was associated with histological grade (p = 0.034), FOXP3 expression was associated with sex and age (p = 0.041, p = 0.003 respectively) and iNOS expression was associated with the disease stage (p = 0.044). In addition, FOXP3 and CD163 appeared to be markers of good prognosis (HR = 0.5407, p = 0.0462; HR = 0.4447, p = 0.0456 respectively). Significant association between PU.1 + and CD68 + macrophages (r = 0.752; P = 0.000) and between PU.1 + and CD163 + macrophages (r = 0.585; P = 0.000) was established, positive association between PU.1 and CD206 expression was also observed (r = 0.424; P = 0.001). Conclusions Large amounts of CD163 + macrophages and FOXP3+ Т-cells appear to be markers of good prognosis of esophageal squamous cell carcinoma. The number of PU.1 + macrophages strongly correlate with the number of CD68 + macrophages therefore usage of PU.1 as a potential macrophage marker can be recommended esophageal tumors.

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The K–Cl Cotransporter KCC3 as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma

BioMed Research International ◽

10.1155/2014/936401 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Atsushi Shiozaki ◽

Kenichi Takemoto ◽

Daisuke Ichikawa ◽

Hitoshi Fujiwara ◽

Hirotaka Konishi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Survival Rate ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Immunohistochemical Analysis ◽

Migration And Invasion ◽

Prognostic Impact ◽

Invasive Front ◽

Cellular Invasion

The objectives of the present study were to investigate the role of K–Cl cotransporter 3 (KCC3) in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT) was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN), and the survival rate of patients with aCN>MTscore was lower than that of patients with aCN≤MTscore. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.

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