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. 2015 Feb 15;8(2):1896-903.
eCollection 2015.

Cancer-associated fibroblasts are associated with poor prognosis in esophageal squamous cell carcinoma after surgery

Yufeng Cheng  1 , Kai Wang  2 , Wei Ma  3 , Xiaomei Zhang  4 , Yipeng Song  5 , Jianbo Wang  4 , Nana Wang  4 , Qingxu Song  4 , Fangli Cao  4 , Bingxu Tan  4 , Jinming Yu  6
Affiliations

Cancer-associated fibroblasts are associated with poor prognosis in esophageal squamous cell carcinoma after surgery

Yufeng Cheng et al. Int J Clin Exp Med. .

Abstract

Objective: Cancer-associated fibroblasts (CAFs; α-SMA positivity), as a representative of the tumor microenvironment, play an important role in influencing the proliferation, invasion and metastasis of cancer cells. The objective is to investigate the prognostic value of CAFs density in esophageal squamous cell carcinoma (ESCC) after surgery.

Method: A total of 95 patients who underwent esophagectomy for ESCC in 2007 were included in this study. These specimens were immunostained with α-smooth muscle actin (α-SMA) antibodies to quantify CAFs. Antibodies D2-40 and CD34 were used to evaluate the lymphatic vessel density (LVD) and microvessel density (MVD) of the lesions. The Cox proportional hazards model was used to determine the hazard ratio of CAFs density on 3-year overall survival and 3-year disease-free survival. The correlation between CAFs density and lymphatic vessel density (LVD) or microvessel density (MVD) were analyzed.

Results: 3-year overall survival rate in the CAF-poor group (63%) was significantly better than those in the CAF-rich group (42%) (P < 0.01). In the Cox univariate and multivariate analysis of 3-year overall survival, the hazard ratio (HR) of CAFs density was 1.870 (95% CI 1.033-3.385; P = 0.039) and 2.196 (95% CI 1.150-4.193; P = 0.017), respectively. CAFs density was proved to be an independent prognostic factor for 3-year overall survival. CAFs density correlated significantly with increased LVD and MVD in ESCC.

Conclusion: CAFs density may be a marker for predicting prognosis and guiding therapeutic management of ESCC.

Keywords: Esophageal squamous cell carcinoma; cancer-associated fibroblasts; lymphatic vessel density; microvessel density; survival.

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Figures

Figure 1
Figure 1
α-SMA-stained 5 μm sections of esophageal squamous cell carcinoma; 100× magnification (10× objective). A. example of CAF-rich (dense overlapping of CAFs distributed throughout the tumor predominantly of epithelioid morphology). B. example of CAF-poor (CAFs not distributed throughout the entire tumor).
Figure 2
Figure 2
Lymphatic vessel density (LVD) D2-40-stained 5 μm sections of esophageal squamous cell carcinoma; 200× magnification (20× objective). The vessels exhibiting a typical morphology (lumen) were considered lymphatic vessels.
Figure 3
Figure 3
microvessel density (MVD) CD34-stained 5 μm sections of esophageal squamous cell carcinoma; 400× magnification (40× objective). The vessels exhibiting a typical morphology were considered microvessel.
Figure 4
Figure 4
3-year survival curves for all 95 patients who underwent esophagectomy for esophageal squamous cell carcinoma. CAF-poor group versus CAF-rich group.
Figure 5
Figure 5
3-year survival curves for patients who received no adjuvant therapy after esophagectomy for esophageal squamous cell carcinoma. CAF-poor group versus CAF-rich group.
Figure 6
Figure 6
3-year survival curves for patients who received adjuvant therapy after esophagectomy for esophageal squamous cell carcinoma. CAF-poor group versus CAF-rich group.
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