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乳腺浸润性导管癌中CD44+/CD24低表型细胞分布特征与预测标志物及分子亚型的关系

Features of CD44+/CD24-low phenotypic cell distribution in relation to predictive markers and molecular subtypes of invasive ductal carcinoma of the breast.

作者信息

Gudadze M, Kankava Q, Mariamidze A, Burkadze G

机构信息

Tbilisi State Medical University; National Cancer Center, Tbilisi, Georgia.

出版信息

Georgian Med News. 2014 Mar(228):81-7.

PMID:24743129
Abstract

Breast cancer is the most widespread pathology among women. Despite the current progresses in research and treatment of metastatic breast cancer, mortality caused by this disease is still high, because above mentioned therapy is limited due to existence of cells resistant to therapy . Cancer stem cells are the only cells with ability of unlimited proliferative activity and cancerous potential, thus, they participate in the growth, progression and dissemination of cancer. Cancer stem cells are resistant to various forms of therapy, including chemotherapy and radiotherapy . Results of examination showed that 50% of all cases are positive on so called markers of stem cells, thus 45% of cases are negative. CD44+/CD24-low cases (cases that reveal stem cell-phenotype) in the group of invasive ductal carcinoma of Luminal A molecular subtype are almost as many as CD44+/CD24+ and CD44-/CD24+ phenotype cancers. In this group non-stem phenotype cases are 65%, so 5 times more than stem cell phenotype cancers. 1324 postoperative breast materials studied through 2008-2012 at the laboratory of "Pathgeo-Union of Pathologists" LTD and Academician N. Kipshidze Central University Clinic were used as test materials and specimens from 393 patients with invasive ductal carcinoma were selected. CD44/CD24 markers' expression in phenotypically different cancers and clinic-pathologic parameters as well as various biological features was conducted by the Pearson's correlation analysis and using X2 test. Statistical analysis of obtained numeral data was held using SPSS V.19.0 program. Confidence interval of 95% was considered statistically significant. Stem cell phenotype positive cases are with the highest percentage represented in Luminal B and basal-like molecular subgroup that to our minds is associated with their aggressive behavior and resistance to chemotherapy. Relatively good prognosis and response to chemotherapy of Luminal A molecular subtype cancers are to be stipulated by lower percentage of cases with stem cells phenotype. With regard to the dimension of cancer the analysis of stem cell phenotype cancers showed that frequency of stem cell phenotype (CD44+/CD24-low) dramatically increases from T1 to T4 cancers. High density of stem cell phenotype cancers in cancers with metastatic lymphatic nodes proves that presence of mentioned phenotype plays a role in progression and dissemination. On the one hand, little amount of stem cells phenotype cancers (CD44+/CD24-low), on the other hand absence of negative cases for markers of stem cell in Her2 subtype makes us consider that come phenotype, close to stem-cell phenotype, plays the leading role in Her2 positive cases.

摘要

乳腺癌是女性中最常见的病理疾病。尽管目前在转移性乳腺癌的研究和治疗方面取得了进展,但这种疾病导致的死亡率仍然很高,因为上述治疗由于存在对治疗耐药的细胞而受到限制。癌症干细胞是唯一具有无限增殖活性和致癌潜能的细胞,因此,它们参与癌症的生长、进展和扩散。癌症干细胞对包括化疗和放疗在内的各种治疗形式都具有抗性。检查结果显示,所有病例中有50%的所谓干细胞标志物呈阳性,因此45%的病例呈阴性。在Luminal A分子亚型的浸润性导管癌组中,CD44+/CD24-low病例(显示干细胞表型的病例)几乎与CD44+/CD24+和CD44-/CD24+表型癌症一样多。在该组中,非干细胞表型病例占65%,是干细胞表型癌症的5倍。2008年至2012年期间在“Pathgeo - 病理学家联盟”有限公司实验室和院士N. 基普希泽中央大学诊所研究的1324份术后乳腺材料用作测试材料,并从393例浸润性导管癌患者中选取标本。通过Pearson相关分析并使用X2检验对表型不同的癌症中CD44/CD24标志物的表达以及临床病理参数和各种生物学特征进行分析。使用SPSS V.19.0程序对获得的数字数据进行统计分析。95%的置信区间被认为具有统计学意义。干细胞表型阳性病例在Luminal B和基底样分子亚组中所占百分比最高,我们认为这与其侵袭性和对化疗的抗性有关。Luminal A分子亚型癌症相对较好的预后和对化疗的反应应归因于干细胞表型病例的较低百分比。关于癌症的大小,对干细胞表型癌症的分析表明,干细胞表型(CD44+/CD24-low)的频率从T1期癌症到T4期癌症急剧增加。有转移性淋巴结的癌症中干细胞表型癌症的高密度证明了上述表型的存在在进展和扩散中起作用。一方面,干细胞表型癌症(CD44+/CD24-low)数量较少,另一方面,Her2亚型中干细胞标志物无阴性病例,这使我们认为接近干细胞表型的某种表型在Her2阳性病例中起主导作用。

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