Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, 450052, People's Republic of China.
Department of Pathology, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
BMC Cancer. 2018 Apr 2;18(1):356. doi: 10.1186/s12885-018-4301-1.
The accumulated evidence has indicated the diagnostic role of cytokeratin (CK) and vimentin protein immunoassay in primary esophageal spindle cell carcinoma (PESC), which is a rare malignant tumor with epithelial and spindle components. However, it is largely unknown for the expression of CK and vimentin in pathological changes and prognosis of PESC.
Eighty-two PESC patients were identified from the esophageal and gastric cardia cancer database established by Henan Key Laboratory for Esophageal Cancer Research of Zhengzhou University. We retrospectively evaluated CK and vimentin protein expressions in PESC. Clinicopathological features were examined by means of univariate and multivariate survival analyses. Furthermore, the co-expression value of cytokeratin and vimentin was analyzed by receiver operating characteristic (ROC) curve.
The positive pan-cytokeratins AE1/AE3 (AE1/AE3 for short) staining was chiefly observed in cytoplasm of epithelial component tumor cells, with a positive detection rate of 85.4% (70/82). Interestingly, 19 cases showed AE1/AE3 positive staining both in epithelial and spindle components (23.2%). However, AE1/AE3 expression was not observed with any significant association with age, gender, tumor location, gross appearance, lymph node metastasis and TNM stage. Furthermore, AE1/AE3 protein expression does not show any effect on survival. Similar results were observed for vimentin immunoassay. However, in comparison with a single protein, the predictive power of AE1/AE3 and vimentin proteins signature was increased apparently than with single signature [0.75 (95% CI = 0.68-0.82) with single protein v.s. 0.89 (95% CI = 0.85-0.94) with AE1/AE3 and vimentin proteins]. The 1-, 3-, 5- and 7-year survival rates for PESC patients in this study were 79.3%, 46.3%, 28.0% and 15.9%, respectively. Multivariate analysis demonstrated age and TNM stage were independent prognostic factors for overall survival (P = 0.036 and 0.003, respectively). It is noteworthy that only 17.1% patients had a PESC accurate diagnosis by biopsy pathology before surgery (14/82). 72.4% PESC patients with biopsy pathology before surgery had been diagnosed as squamous cell carcinoma.
The present study demonstrates that cytokeratin and vimentin protein immunoassay is a useful biomarker for PESC accurate diagnosis, but not prognosis. The co-expression of cytokeratin and vimentin in both epithelial and spindle components suggest the possibility of single clone origination for PESC.
已有大量证据表明细胞角蛋白(CK)和波形蛋白免疫组化在原发性食管梭形细胞癌(PESC)中的诊断作用,PESC 是一种罕见的具有上皮和梭形成分的恶性肿瘤。然而,CK 和波形蛋白在 PESC 的病理变化和预后中的表达情况尚不清楚。
从郑州大学食管癌河南省重点实验室建立的食管和贲门癌数据库中确定了 82 例 PESC 患者。我们回顾性评估了 PESC 中 CK 和波形蛋白的蛋白表达情况。通过单变量和多变量生存分析检查临床病理特征。此外,通过接收者操作特征(ROC)曲线分析细胞角蛋白和波形蛋白的共表达值。
上皮成分肿瘤细胞的细胞质中主要观察到广谱细胞角蛋白 AE1/AE3(简称 AE1/AE3)染色阳性,阳性检出率为 85.4%(70/82)。有趣的是,19 例上皮和梭形成分均显示 AE1/AE3 阳性染色(23.2%)。然而,AE1/AE3 表达与年龄、性别、肿瘤部位、大体外观、淋巴结转移和 TNM 分期均无显著相关性。此外,AE1/AE3 蛋白表达对生存没有影响。波形蛋白免疫组化也观察到类似的结果。然而,与单个蛋白相比,AE1/AE3 和波形蛋白蛋白标志物的预测能力明显提高[单个蛋白为 0.75(95%CI=0.68-0.82),AE1/AE3 和波形蛋白蛋白为 0.89(95%CI=0.85-0.94)]。本研究中 PESC 患者的 1、3、5 和 7 年生存率分别为 79.3%、46.3%、28.0%和 15.9%。多变量分析表明,年龄和 TNM 分期是总生存的独立预后因素(P=0.036 和 0.003)。值得注意的是,仅 17.1%(14/82)的患者在术前通过活检病理得到了准确的 PESC 诊断。72.4%(68/82)的 PESC 患者在术前通过活检病理诊断为鳞状细胞癌。
本研究表明,细胞角蛋白和波形蛋白免疫组化是 PESC 准确诊断的有用生物标志物,但不是预后标志物。上皮和梭形成分中细胞角蛋白和波形蛋白的共表达提示 PESC 可能起源于单个克隆。