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乳腺癌导管原位癌和浸润性导管癌中癌症干细胞标志物 CD44、CD24、VEGF 和 HIF-1α 的临床病理相关性:一项基于免疫组织化学的初步研究。

Clinicopathologic correlation of cancer stem cell markers CD44, CD24, VEGF and HIF-1α in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study.

机构信息

The Ultrasonagraphy Center of Second Affiliated Hospital of Soochow University, Sanxiang Road, Suzhou 215004, PR China.

出版信息

Pathol Res Pract. 2011 Aug 15;207(8):505-13. doi: 10.1016/j.prp.2011.06.009. Epub 2011 Jul 28.

DOI:10.1016/j.prp.2011.06.009
PMID:21802218
Abstract

CD24(-/low)CD44(+) cells have been identified as putative cancer stem cells (CSCs) in breast cancer. However, the expression of these markers, as well as their association with clinical parameters or tumor microenvironment of breast cancer, remains largely unknown. In the present study, we examined the expression of CD44, CD24, VEGF, and HIF-1α in human breast tumor tissues and assessed their clinicopathological correlations. We investigated tissue samples, including 117 cases of invasive ductal carcinoma (IDCa), 14 cases of ductal carcinoma in situ (DCIS), and 15 cases of intraductal hyperplasia (IDH) from breast tissues. The expression of CD44, CD24, HIF-1α, and VEGF was evaluated using immunohistochemical staining. CD24, CD44, HIF-1α, and VEGF were expressed in 49 (41.9%), 51 (43.6%), 32 (27.4%), and 97 cases (82.9%), respectively, in IDCa. CD24(-/low)CD44(+) cells were noted in 48 (41.3%) cases. The levels of CD24 and VEGF expression correlated positively with tumor malignancy (P<0.05). Meanwhile, the expression of CD24, CD44, and VEGF correlated significantly positively with increasing tumor grade (P<0.05). In addition, associations between CD44 and VEGF, CD24 and VEGF, HIF-1α and VEGF, CD24(-/low)CD44(+) and VEGF, CD24(-/low)CD44(+) and HIF-1α were also observed (P<0.05). The HIF-1α expression level was relatively higher in early stage breast cancer patients with CD24(-/low)CD44(+) cells. Taken together, our results suggest that CD24 and VEGF may play important roles in breast tumorigenesis and progression, while HIF-1α may play a role in the early stage of breast carcinogenesis.

摘要

CD24(-/low)CD44(+)细胞已被鉴定为乳腺癌中的癌症干细胞(CSC)。然而,这些标志物的表达及其与乳腺癌临床参数或肿瘤微环境的关系在很大程度上仍然未知。在本研究中,我们检测了人乳腺癌组织中 CD44、CD24、VEGF 和 HIF-1α 的表达,并评估了它们与临床病理参数的相关性。我们研究了组织样本,包括来自乳腺组织的 117 例浸润性导管癌(IDCa)、14 例导管原位癌(DCIS)和 15 例导管内增生(IDH)。使用免疫组织化学染色评估 CD44、CD24、HIF-1α 和 VEGF 的表达。在 IDCa 中,CD24、CD44、HIF-1α 和 VEGF 的表达分别为 49(41.9%)、51(43.6%)、32(27.4%)和 97 例(82.9%)。在 48 例(41.3%)病例中观察到 CD24(-/low)CD44(+)细胞。CD24 和 VEGF 的表达水平与肿瘤恶性程度呈正相关(P<0.05)。同时,CD24、CD44 和 VEGF 的表达与肿瘤分级的增加显著正相关(P<0.05)。此外,还观察到 CD44 与 VEGF、CD24 与 VEGF、HIF-1α 与 VEGF、CD24(-/low)CD44(+)与 VEGF、CD24(-/low)CD44(+)与 HIF-1α 之间存在相关性(P<0.05)。在 CD24(-/low)CD44(+)细胞的早期乳腺癌患者中,HIF-1α 的表达水平相对较高。综上所述,我们的研究结果表明,CD24 和 VEGF 可能在乳腺癌的发生和发展中发挥重要作用,而 HIF-1α 可能在乳腺癌发生的早期阶段发挥作用。

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