Claudin-Low Breast Cancer; Clinical & Pathological Characteristics.
Claudin-Low Breast Cancer; Clinical & Pathological Characteristics.
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DOI：
10.1371/journal.pone.0168669
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Bane AL
中科院分区：
文献类型：
--
作者：
Dias K;Dvorkin-Gheva A;Hallett RM;Wu Y;Hassell J;Pond GR;Levine M;Whelan T;Bane AL
低密蛋白乳腺癌是一种最初通过基因表达谱鉴定的分子类型的乳腺癌，据报道与生存率低相关。已经认识到低密蛋白肿瘤优先显示三阴性表型，然而只有少数三阴性乳腺癌是低密蛋白的。我们试图确定一个免疫组化的claudin低肿瘤，可以帮助他们在福尔马林固定石蜡包埋的肿瘤材料的识别。首先，组装了约1600个人乳腺癌表达谱的计算机收集，并鉴定了所有低密蛋白肿瘤。第二，确定了在低密蛋白肿瘤和所有其他乳腺癌分子亚型之间差异表达的基因。第三，使用免疫组织化学测试了这些顶级差异表达基因中的一些在不同的乳腺癌细胞系中的表达，以确定它们对低密蛋白肿瘤的特异性。最后，在942例福尔马林固定石蜡包埋的人乳腺癌队列中检查了被发现是低密蛋白肿瘤的最特征的免疫组织化学组，并进行了>10年的临床随访，以评估该肿瘤亚型的临床病理学和生存特征。使用这种方法，我们确定了密蛋白低乳腺癌通常对ER、PR、HER 2、密蛋白3、密蛋白4、密蛋白7和E-钙粘蛋白呈阴性。用免疫组化鉴定的Claudin-低水平肿瘤与发病年龄小、肿瘤分级高、肿瘤大小大、广泛的淋巴细胞浸润和肿瘤边缘界限清楚有关。与管腔A型乳腺癌患者相比，低密蛋白肿瘤患者的总体生存率更差。有趣的是，低密蛋白肿瘤与保乳治疗后的低局部复发率相关。总之，有限的一组抗体可以帮助识别claudin低的肿瘤。此外，以这种方式鉴定的低密蛋白肿瘤显示出与使用基因表达谱从新鲜冷冻肿瘤材料鉴定的低密蛋白肿瘤相似的临床、病理和存活特征。
Claudin-low breast cancer is a molecular type of breast cancer originally identified by gene expression profiling and reportedly associated with poor survival. Claudin-low tumors have been recognised to preferentially display a triple-negative phenotype, however only a minority of triple-negative breast cancers are claudin-low. We sought to identify an immunohistochemical profile for claudin-low tumors that could facilitate their identification in formalin fixed paraffin embedded tumor material. First, an in silico collection of ~1600 human breast cancer expression profiles was assembled and all claudin-low tumors identified. Second, genes differentially expressed between claudin-low tumors and all other molecular subtypes of breast cancer were identified. Third, a number of these top differentially expressed genes were tested using immunohistochemistry for expression in a diverse panel of breast cancer cell lines to determine their specificity for claudin-low tumors. Finally, the immunohistochemical panel found to be most characteristic of claudin-low tumors was examined in a cohort of 942 formalin fixed paraffin embedded human breast cancers with >10 years clinical follow-up to evaluate the clinico-pathologic and survival characteristics of this tumor subtype. Using this approach we determined that claudin-low breast cancer is typically negative for ER, PR, HER2, claudin 3, claudin 4, claudin 7 and E-cadherin. Claudin-low tumors identified with this immunohistochemical panel, were associated with young age of onset, higher tumor grade, larger tumor size, extensive lymphocytic infiltrate and a circumscribed tumor margin. Patients with claudin-low tumors had a worse overall survival when compared to patients with luminal A type breast cancer. Interestingly, claudin-low tumors were associated with a low local recurrence rate following breast conserving therapy. In conclusion, a limited panel of antibodies can facilitate the identification of claudin-low tumors. Furthermore, claudin-low tumors identified in this manner display similar clinical, pathologic and survival characteristics to claudin-low tumors identified from fresh frozen tumor material using gene expression profiling.
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影响因子：
11.2
作者：
Hollier BG;Tinnirello AA;Werden SJ;Evans KW;Taube JH;Sarkar TR;Sphyris N;Shariati M;Kumar SV;Battula VL;Herschkowitz JI;Guerra R;Chang JT;Miura N;Rosen JM;Mani SA
通讯作者：
Mani SA
影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
5.8
作者：
Benito, M;Parker, J;Marron, JS
通讯作者：
Marron, JS
影响因子：
2.5
作者：
Creighton, Chad J.;Chang, Jenny C.;Rosen, Jeffrey M.
通讯作者：
Rosen, Jeffrey M.
影响因子：
8
作者：
Farmer, P;Bonnefoi, H;Iggo, R
通讯作者：
Iggo, R