Clinical significance of cytokeratin 19 and OCT4 as survival markers in non-metastatic and metastatic breast cancer patients

L. Abdelaziz., H. Ebian, O. Harb, Yousef Nosery, Heba F. Taha, Nashwa Nawar
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Abstract

Introduction Cytokeratin 19 (CK19) is highly expressed in epithelial tumours such as breast cancer (BC). Octamer-binding transcription factor 4 (OCT4), a transcription factor of the POU (Pit-Oct-UNC) family, plays a criti-cal role in the self-renewal and maintenance of pluripotency of embryonic stem cells; therefore, it has been used as a promising CSC marker. Material and methods CK19 was assessed in peripheral blood using flow-cytometric analysis while OCT4 was evaluated in breast tissue samples by immunohistochemistry from 70 patients (non-metastatic BC, meta-static BC, and non-malignant breast tumours). Results CK19 and OCT4 were significantly associated with BC patients compared to control (p < 0.001). CK19 was detected in 38 patients with BC (62.2%); meanwhile, OCT4 was positive in 37 BC patients (60.6%). CK19 was positively associated with grade (p = 0.002), HER2 (p = 0.009), metastasis (p = 0.026), molecular subtypes and LN (p < 0.001), and stage (p = 0.001) while OCT4 expression was positively associated with BMI (p < 0.023), aggressive molecular subtype (p < 0.019), ER expression (p = 0.025), presence of LN metastases (p < 0.017), and distant metastasis (p < 0.018). A non-significant relation was found between the expression of CK19 and OCT (p = 0.291). The positive expression of CK19 and OCT4 was significantly and inversely associated with both 3-year OS and 3-year PFS. Conclusions CK19 and OCT4 are associated with BC, so they can be considered as prognostic and predictive markers for poor OS and PFS in non-metastatic as well as metastatic BC patients.
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细胞角蛋白19和OCT4作为非转移性和转移性乳腺癌患者生存标志物的临床意义
细胞角蛋白19 (CK19)在上皮性肿瘤如乳腺癌(BC)中高表达。八聚体结合转录因子4 (OCT4)是POU (Pit-Oct-UNC)家族的一种转录因子,在胚胎干细胞的自我更新和多能性维持中起着关键作用;因此,它已成为一种有前景的CSC标记物。材料和方法采用流式细胞术分析外周血中CK19的含量,采用免疫组化方法评估70例患者(非转移性BC、元静态BC和非恶性乳腺肿瘤)乳腺组织样本中的OCT4含量。结果与对照组相比,CK19和OCT4与BC患者有显著相关性(p < 0.001)。38例BC患者检测到CK19 (62.2%);同时,37例BC患者OCT4阳性(60.6%)。CK19与肿瘤分级(p = 0.002)、HER2 (p = 0.009)、转移(p = 0.026)、分子亚型、淋巴结转移(p < 0.001)、分期(p = 0.001)呈正相关,而OCT4表达与BMI (p < 0.023)、侵袭性分子亚型(p < 0.019)、ER表达(p = 0.025)、淋巴结转移(p < 0.017)、远处转移(p < 0.018)呈正相关。CK19的表达与OCT无显著相关(p = 0.291)。CK19和OCT4的阳性表达与3年OS和3年PFS呈显著负相关。结论CK19和OCT4与BC相关,可作为非转移性和转移性BC患者不良OS和PFS的预后和预测指标。
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