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目的研究乳腺浸润性微乳头状癌(invasive micropapillary carcinoma,I MPC)的干细胞表型,从干细胞和上皮间质转化(epithelial-mesenchymal transition,EMT)角度探讨I MPC高侵袭、高转移恶性生物学行为的原因。方法选取术前未经放化疗治疗患者的I MPC82例和乳腺非特殊型浸润性导管癌(invasive ductal carcinoma nototherwise specified,IDC-NOS)80例石蜡包埋组织标本切片,通过免疫组织化学双染技术检测两组肿瘤组织中CD44+/CD24-/low(CD24-)和CD24+的表达、定位和分布情况,并分析其与各临床病理学特征之间的关系。定量资料采用Student’st检验,定性资料采用Mann-Whitney U检验、Kruskal-Wallis检验、χ2检验或校正χ2检验。两组之间相关性采用Spearman’s秩相关分析。结果(1)I MPC组肿瘤细胞的CD44+/CD24-/low阳性表达率(48.8%,40/82例),明显高于IDC-NOS组(31.3%,25/80例)(χ2=5.180,P=0.023)。(2)53.7%(44/82例)的I MPC微细间质组织内见单个散在的CD44+/CD24-/low肿瘤细胞,且该细胞免疫组织化学染色Vi mentin及α-SMA阳性,E-Cadherin阴性。IDC-NOS间质内罕见CD44+/CD24-/low肿瘤细胞。(3)I MPC微乳头结构中CD44+/CD24-/low与间质内的CD44+/CD24-/low阳性表达细胞呈明显正相关(r=0.516,P<0.001),并且I MPC微乳头结构及间质中CD44+/CD24-/low阳性表达在有无淋巴管侵犯和有无淋巴结外软组织浸润方面的差异均有统计学意义(P<0.050),即有淋巴管侵犯及淋巴结外软组织浸润者CD44+/CD24-/low阳性表达率较高。(4)I MPC组中CD24+细胞阳性表达率79.3%(65/82例),明显高于IDC-NOS组(60.0%,48/80例)(χ2=7.126,P=0.008),且I MPC中淋巴结转移阳性组CD24的表达高于阴性组,差异有统计学意义(χ2=8.834,P=0.003)。结论I MPC肿瘤细胞中干细胞的存在及上皮间质转化可能是I MPC高淋巴管侵犯、高淋巴结转移及耐药等恶性生物学行为的重要原因。研发针对乳腺癌干细胞的药物也可作为治疗乳腺癌的一个方法。
OBJECTIVE: To study the stem cell phenotype of invasive micropapillary carcinoma (I MPC) and to investigate the high invasion and metastatic malignant behavior of I MPC from the perspective of stem cell and epithelial-mesenchymal transition (EMT) s reason. Methods Eighty-two cases of I MPC and 80 cases of invasive ductal carcinoma nototherwise carcinoma (IDC-NOS) were enrolled in this study. Paraffin-embedded tissue sections were obtained by immunohistochemical double staining The expression, localization and distribution of CD44 + / CD24- / low (CD24-) and CD24 + in the two groups of tumor tissues were detected and their relationships with clinicopathological features were analyzed. Quantitative data using Student’st test, qualitative data using Mann-Whitney U test, Kruskal-Wallis test, χ2 test or correction χ2 test. The correlation between the two groups using Spearman’s rank correlation analysis. Results The positive rates of CD44 + / CD24- / low in I MPC group (48.8%, 40/82) were significantly higher than those in IDC-NOS group (31.3%, 25/80) (χ2 = 5.180, P = 0.023). (2) A single scattered CD44 + / CD24- / low tumor cells were found in 53.7% (44/82) of I MPC interstitial tissues, and the cells were positive for Vimentin and α-SMA in immunohistochemical staining. E-Cadherin negative. IDC-NOS interstitial rare CD44 + / CD24- / low tumor cells. (3) There was a significant positive correlation between CD44 + / CD24- / low and interstitial CD44 + / CD24- / low positive cells in the I MPC micro-papillary structure (r = 0.516, P <0.001) There were significant differences in the expression of CD44 + / CD24- / low in the interstitium between lymphatic invasion and non-lymph node infiltration (P <0.050), that is, lymphatic invasion and lymph node infiltration of CD44 + / CD24- / low higher positive rate. (4) The positive rate of CD24 + cells in I MPC group was 79.3% (65/82), which was significantly higher than IDC-NOS group (60.0%, 48/80) (χ2 = 7.126, P = 0.008) The expression of CD24 in the group of positive lymph node metastasis was higher than that in the negative group (χ2 = 8.834, P = 0.003). Conclusion The existence of stem cells and epithelial-mesenchymal transition in I MPC tumor cells may be the important reason for the malignant biological behaviors such as lymphangiogenesis, lymph node metastasis and drug resistance in I MPC. R & D for breast cancer stem cells can also be used as a treatment for breast cancer.