三陰性乳腺癌組織中腫瘤干細胞相關標記物CD44+/CD24—/low和ALDH1+的表達及意義

王安安　吳恒宇　劉磊

【摘要】 目的：探討三陰性乳腺癌（TNBC）組織中乙醛脫氫酶1（aldehyde dehydrogenases l，ALDH1）和CD44+/CD24-/low的表達及其與臨床預后的關系。方法：通過免疫組織化學SP法檢測ALDH1和CD44+/CD24-/low等生物學指標在30例三陰性乳腺癌（TNBC）術后石蠟切片組織和30例非三陰性乳腺癌術后石蠟切片組織中的表達，并分析其與TNBC的臨床預后因素的關系。結果：TNBC組織中ALDH1+表達率為46.67%，CD44+/CD24-/low陽性表達率為56.67%；非三陰性乳腺癌組織中ALDH1+表達率為16.67%，CD44+/CD24-/low陽性表達率為26.67%，TNBC組織中ALDH1和CD44+/CD24-/low陽性表達率明顯高于非三陰性乳腺組織，兩者比較差異有統計學意義（P<0.05）。腋窩淋巴結轉移率在CD44+/CD24-/low與ALDH1均陽性表達組和非陽性表達組中分別為66.67%和23.81%（ 字2=4.983，P=0.035）；局部復發和/或轉移率分別為33.34%和0（ 字2=7.778，P=0.021）。結論：TNBC組織中ALDH1+和CD44+/CD24-/low過表達，可以作為判斷TNBC患者預后的標記物。

【關鍵詞】 三陰性乳腺癌； ALDH1； CD44+/CD24-/low； 預后

【Abstract】 Objective：To investigate the expression and relationship with clinical prognosis of aldehyde dehydrogenase 1 （ALDH1） and the CD44+/CD24-/low in triple negative breast cancer （TNBC） organization.Method：ALDH1

and CD44+/CD24-/low biological index was detected by immunohistochemical SP method in 30 cases of triple negative breast cancer （TNBC） postoperative paraffin tissue and 30 cases of non-triple negative breast cancer postoperative paraffin tissue，and its relationship with the clinical prognostic factors was analyzed.Result：The expression rate of ALDH1+ in TNBC was 46.67% and in non-triple negative breast cancer tissue was 16.67% respectively，the expression rate of CD44+/CD24-/low in TNBC was 56.67% and in non-triple negative breast cancer tissue was 26.67% respectively，the difference was statistically significant（P<0.05）.The positive expression rates of ALDH1 and CD44+/CD24-/low in TNBC tissue was significantly higher than in the non-triple negative breast cancer tissue.Axillary lymph node metastasis rate in CD44+/CD24-/low and ALDH1 both positive expression group and the non positive expression group were 66.67% and 23.81% respectively （ 字2=4.983，P=4.983）.Local recurrence and/or metastasis rates were 33.34% and 0 respectively （ 字2=7.778，P=7.778）.Conclusion：Overexpression of ALDH1+ and CD44+/CD24-/low may be used as a marker for the prognosis of patients with TNBC subtype.

【Key words】 Triple negative breast cancer； ALDH1； CD44+/CD24-/low； Prognosis

First-authors address：The Second Affiliated Hospital of Nanchang University，Nanchang 330006，China

doi：10.3969/j.issn.1674-4985.2017.25.006

乳腺癌是目前威脅女性生命健康最常見的惡性腫瘤之一，三陰性乳腺癌（triple-negative breast cancer，TNBC）最早是由Sorlie等[1]提出，指雌激素受體（estrogen receptor，ER）、孕激素受體（progesterone receptor，PR）和人表皮生長因子受體2（human epidermal growth factor receptor-2，HER2）均為陰性的一類乳腺癌，占基底細胞樣型（basal-like）型的80%～90%，具有侵襲性強和容易遠處轉移的臨床病理特征，并且臨床上缺乏有效的內分泌治療和抗HER-2靶向治療，缺乏有效的預測指標來檢驗其治療效果，因此在乳癌分子亞型中預后最差。CD44+/CD24-/low或ALDH1+目前公認的乳癌干細胞標志物，2003年Al-Hajj等[2]發現CD44+/CD24-/low表型的乳腺癌細胞可以作為乳腺腫瘤干細胞（breast cancer stem cell，BCSCs），具有自我更新和多向分化成瘤的能力，是惡性腫瘤轉移復發的基礎，并且在細胞成瘤實驗中，具有很強的成瘤能力和轉移能力。隨后Ginestier等[3]證實ALDH1+乳腺癌細胞也具有乳腺癌干細胞特性，并且發現其表達與乳腺癌患者預后差有關。目前乳腺癌研究中，多局限于ALDH1+和CD44+/CD24-/low各自的表達情況，有關二者在三陰性乳腺癌預后作用價值的報道尚少，且存有爭議。……