乳腺浸润微乳头状癌中乙醛脱氢酶-1表型细胞的研究

Study on aldehyde dehydrogenase-1 tumor cells in invasive micropapillary carcinoma of the breast

目的：探讨肿瘤干细胞标志物乙醛脱氢酶-1（aldehyde dehydrogenase-1，ALDH-1）在乳腺浸润性微乳头状癌（ invasive micropapillary carcinoma ，IMPC）原发灶及淋巴结转移灶中的表达及临床意义。方法选取乳腺IMPC伴淋巴结转移103例和非特殊型浸润性导管癌伴淋巴结转移（ invasive ductal carci-noma not otherwise specified ，IDC-NOS）110例的石蜡包埋组织标本，所有入选病例术前均未经放、化疗治疗。免疫组织化学染色技术检测2组肿瘤原发灶和相应的淋巴结转移灶癌组织中ALDH-1的表达、定位和分布情况，并分析其与乳腺癌各临床病理学特征之间的关系及预后意义。结果①IMPC组原发灶及淋巴结转移灶中肿瘤细胞 ALDH-1阳性表达率[原发灶37.9％（39/103）；淋巴结转移灶47.6％（49/103）]，明显高于IDC-NOS组[原发灶21.8％（24/110）；淋巴结转移灶23.6％（26/110）]，差异有统计学意义（P＜0.05）。②IMPC原发灶及淋巴结转移灶中肿瘤细胞ALDH-1阳性表达与患者的肿瘤大小、组织学分级、淋巴结转移、ER阴性状态、PR阴性状态、HER2过表达呈明显正相关（P＜0.05）。③与IDC-NOS组相比，IMPC组患者的无病生存期明显缩短，差异具有统计学意义（ P＝0.003）。淋巴结阳性乳腺IMPC原发灶及淋巴结转移灶肿瘤细胞中 ALDH-1蛋白阳性表达患者的无病生存期明显低于其阴性表达患者，差异有统计学意义（ P＜0.05）。多因素分析乳腺IMPC转移淋巴结中ALDH-1蛋白阳性表达与患者的预后差有关（P＝0.005）。结论 ALDH-1可作为淋巴结阳性乳腺IMPC患者预后不良的指标，且IMPC肿瘤细胞中干细胞的存在可能是导致IMPC高淋巴管侵袭、高淋巴结转移及耐药等恶性生物学行为的重要原因。

Objective To investigate the expression of tumor stem cell marker aldehyde dehydrogenase -1 （ALDH-1）in primary tumor and lymph node metastases of lymph node-positive invasive micropapillary carcinoma （ IMPC） of breast and its clinical significance .Methods The expression , location and distribution of ALDH-1 were examined by immunohistochemical staining in 103 cases with lymph node metastasis of IMPC and 110 cases with lymph node metastasis of invasive ductal carcinoma not otherwise specified （ IDC-NOS） without preoperative chemotherapy and radiotherapy , and their relationship with clinicopathological characteristics and prognostic sig-nificance was analyzed .Results （ 1 ） The positive expression rate of ALDH-1 was significantly higher in IMPC group of primary tumor and lymph node metastases （37.9% in primary tumor, 39/103 cases;47.6% in lymph node metastases, 49/103 cases）than in IDC-NOS group（21.8% in primary tumor, 24/110 cases; 23.6% in lymph node metastases, 26/110 cases）（P＆lt;0.05）.（2）Expression of ALDH-1 had a significantly positive corre-lation with tumor size , histological grade , lymph node metastasis , ER-negative status , PR-negative status , and HER2 overexpression in primary tumor and lymph node metastases of IMPC （P＆lt;0.05）.（3）The disease-free sur-vival of IMPC group patients was significantly shorter than that of IDC-NOS group patients（P=0.003）.In IPMC patients with lymphode metastases , the disease-free survival of patients with ALDH-1 positive in primary tumor and lymph node was significantly lower than patients with ALDH-1 negative expression （P＆lt;0.05）.In multivari-ate analysis, positive expression of ALDH-1 in metastatic lesions was associated with worse prognosis （ P =0.005）.Conclusion ALDH-1 can be used as an independent factor for predicting prognosis of patients with lymph node-positive breast IMPC and the existence of stem cells in IMPC tumor cells may represent high IMPC lymphatic invasion , lymph node metastasis and high resistance .