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中华乳腺病杂志(电子版) ›› 2009, Vol. 03 ›› Issue (05) : 524 -534. doi: 10.3877/cma.j.issn.1674-0807.2009.05.010

实验研究

乳腺浸润性微乳头状癌中CD44+/CD24-/low和CD24+表型细胞的研究
李伟东1, 刘芳芳1, 徐新生1, 刘冰冰1, 崔力方1, 位嘉1, 郭晓静1, 郎荣刚1, 范宇1, 谷峰1, 付丽1,()   
  1. 1.300060 天津,天津医科大学附属肿瘤医院乳腺病理科教育部乳腺癌防治重点实验室
  • 收稿日期:2009-06-19 出版日期:2009-10-01
  • 通信作者: 付丽
  • 基金资助:
    教育部长江学者和创新团队发展计划资助项目(IRT0743)国家自然科学基金资助项目(30600225)国家“863”计划项目(2006 AA02 A249)国家“973”计划资助项目(2009CB521700)

Study on CD44+/CD24-/low and CD24+tu mor cells in invasive micropapillary carcinoma of the breast

Wei-dong LI1, Fang-fang LIU1, Xin-sheng XU1, Bing-bing LIU1, Li-fang CUI1, Jia WEI1, Xiao-jing GUO1, Rong-gang LANG1, Yu FAN1, Feng GU1, Li FU,1()   

  1. 1.Department of Breast Cancer Pathology and Research Laboratory,Cancer Institution and Hospital,Tianjin Medical University,Tianjin 300060,China
  • Received:2009-06-19 Published:2009-10-01
  • Corresponding author: Li FU
引用本文:

李伟东, 刘芳芳, 徐新生, 刘冰冰, 崔力方, 位嘉, 郭晓静, 郎荣刚, 范宇, 谷峰, 付丽. 乳腺浸润性微乳头状癌中CD44+/CD24-/low和CD24+表型细胞的研究[J/OL]. 中华乳腺病杂志(电子版), 2009, 03(05): 524-534.

Wei-dong LI, Fang-fang LIU, Xin-sheng XU, Bing-bing LIU, Li-fang CUI, Jia WEI, Xiao-jing GUO, Rong-gang LANG, Yu FAN, Feng GU, Li FU. Study on CD44+/CD24-/low and CD24+tu mor cells in invasive micropapillary carcinoma of the breast[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2009, 03(05): 524-534.

目的

研究乳腺浸润性微乳头状癌(invasive micropapillary carcinoma,IMPC)的干细胞表型,从干细胞和上皮间质转化(epithelial-mesenchy mal 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 MPC 82 例和乳腺非特殊型浸润性导管癌(invasive ductal carcinoma not other wise 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's t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Spear man'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 micr opapillary carcino ma(I MPC)of the breast.Through the stem cell and epithelial-mesenchy mal transition,the causes of biological behaviour of high metastasis and invasion of IMPC was investigated.

Methods

The expression,l ocation and distribution of CD44 and CD24 were deter mined by immunohistochemical double staining in 82 cases of IMPC and 80 cases of invasive ductal carcino ma not other wise specified (IDC-NOS),under going without preoperative chemot herapy and radiot herapy, and their relationship with clinicopat hological feat ures was anal yzed.St udent'st test was used for quantitative data.Mann-Whitney Utest,Kruskal-Wallis test andχ2 test or revisedχ2 test were used for qualitative data.Spear man's test was used for association bet ween groups.

Results

The positive expression rate of CD44+/CD24-/low tumor cells was higher in the IMPC gr oup(48.8%,40/82 cases)t han in the IDC-NOS gr oup(31.3%,25/80 cases)(χ2=5.180,P=0.023).The CD44+/CD24-/low tu mor cells was also detected in adjacent stro ma surrounding the micropapillary structure in 53.7%(44/82 cases)of I MPC,with Vi mentin andα-SMA positive and E-Cadherin negative,but scarce in stro ma of IDC-NOS.(3)The CD44+/CD24-/low tu mor cells in micr opapillar y str ucture of IMPC was positively associated with that instroma(r=0.516,P<0.001),moreover,they were bot h associated withly mphovascular invasion and extranodal extension respectively,and there was statistical difference between lymphovascular invasion and extranodal extension(P<0.050),that is the positive expression rate of CD44+/CD24-/low in ly mphovascular invasion and extranodal extension was high.(4)The positive expression rate of CD24+t u mor cells was also higher in IMPC (65/82 cases)than in IDC-NOS(48/80 cases)(χ2=7.126,P=0.008),and in IMPC the expression of CD24+ was higher in positively mphnode metastasis than in negative,with statistical difference(χ2=8.834,P=0.003).

Conclusions

The existence of stem cells and epithelial-mesenchy mal transition in IMPC tumor cells may play an important rolein aggressiveness and higher metastatic risk of IMPC of the breast.It can be a method to develop drugs targeting breast cancer stemcells.

表1 I MPC 和IDC-NOS临床病理学特征的比较
图1 乳腺癌组织中CD44和CD24的表达 a:箭头所示IDC-NOS中CD44+/CD24-/low表型肿瘤细胞,而CD24阴性表达(×200);b:箭头所示IMPC微乳头结构中的CD44+/CD24-/low表型肿瘤细胞(×200);c:箭头所示IMPC微乳头结构周围间质组织中的CD44+/CD24-/low表型肿瘤细胞(×200);d:箭头所示IMPC微乳头结构周围间质组织中的CD44+/CD24-/low表型肿瘤细胞,与此相反,相邻的IMPC微乳头结构中的肿瘤细胞为CD24+表型(×400);CD44以AP-red显色,红色为阳性表达;CD24以DAB显色,棕色为阳性表达。
图2 免疫组织化学染色显示I MPC间质组织中肿瘤细胞E-CD 和Vi mentin的表达 a:E-CD 在I MPC 微乳头状结构与间质相接的外侧面低表达或表达缺失,而微乳头中间部分的肿瘤细胞间正常表达或高表达;I MPC微乳头周围间质组织中少数单个散在的肿瘤细胞可见E-CD 呈阴性表达(箭头所示)(SP ×200);b:I MPC微乳头周围间质中单个散在的肿瘤细胞与其周围其他间质细胞相同,显示Vi mentin阳性表达(箭头所示),而微乳头结构中的肿瘤细胞团却与之相反,显示Vi mentin阴性表达(SP ×200)。
表2 IMPC间质和微乳头结构中CD44+/CD24-/low(CD24-)细胞的关系
表3 I MPC 临床病理学特征与CD44+/CD24-/low和CD24+肿瘤细胞的关系
表4 I MPC 间质和微乳头结构中CD44+/CD24-/low细胞与淋巴管侵犯及淋巴结外软组织浸润的关系
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