Nectin-4 is a new histological and serological tumor associated marker for breast cancer.
Nectin-4 is a new histological and serological tumor associated marker for breast cancer.
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DOI：
10.1186/1471-2407-7-73
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发表时间：
2007-05-02
期刊：
影响因子：
3.8
通讯作者：
Lopez M
中科院分区：
文献类型：
--
作者：
Fabre-Lafay S;Monville F;Garrido-Urbani S;Berruyer-Pouyet C;Ginestier C;Reymond N;Finetti P;Sauvan R;Adélaïde J;Geneix J;Lecocq E;Popovici C;Dubreuil P;Viens P;Gonçalves A;Charafe-Jauffret E;Jacquemier J;Birnbaum D;Lopez M
乳腺癌在分子水平上是一种复杂的异质性疾病。根据经典的组织临床预后因素很难预测预后。不同的研究强调了大规模分子表达分析对改进乳腺癌分类和预后分类的重要性。寻找新的分子标记来完善这一分类并改善患者管理是乳腺癌研究领域的优先事项。果胶是参与调节上皮生理的细胞黏附分子。我们在此提出Nectin-4/PVRL4作为一种新的乳腺癌组织学和血清学肿瘤相关标记物。应用流式细胞术和免疫组织化学方法分别检测78个不同来源的原代细胞和细胞系和57个乳腺肿瘤组织中Nectin-4蛋白的表达。用定量聚合酶链式反应检测mRNA的表达。用双抗体夹心ELISA法检测45例健康献血员、53例初诊非转移性乳腺癌(MBC)患者和182例MBC患者血清Nectin-4，并与CEA和CA15.3进行比较。用标准CHI-2检验比较组织学/血清学分子标志物和组织临床参数的分布。正常乳腺组织中未检测到Nectin-4的表达。相比之下，Nectin-4在导管型乳腺癌中的阳性表达率为61%，在小叶型乳腺癌中的阳性表达率为6%。Nectin-4的表达与基底细胞样标记物EGFR、P53、P-cadherin呈显著正相关，与管腔样标记物ER、PR、GATA3呈负相关。除1例ER/PR阴性肿瘤外，其余肿瘤均表达Nectin-4。血清中Nectin-4的检测改善了MBC患者的随访：CEA/CA15.3/Nectin-4联合检测可以监测74%的这些患者，而CEA/CA15.3联合检测只有67%。血清Nectin-4是疾病进展的标志，其水平与转移的数目相关(P=0.038)。血清Nectin-4也是疗效的标志，在90%的病例中，与临床进展相关。Nectin-4是一种新的乳腺癌相关抗原。Nectin-4是一种新的生物标志物，它的使用可以帮助完善乳腺癌的分类，改善患者的随访。Nectin-4是乳腺癌免疫治疗的潜在靶点。
Breast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research. Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma. Expression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC), respectively. mRNA expression was measured by quantitative PCR. Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC) at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test. Nectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels correlate with the number of metastases (P = 0.038). Serum Nectin-4 is also a marker of therapeutic efficiency and correlates, in 90% of cases, with clinical evolution. Nectin-4 is a new tumor-associated antigen for breast carcinoma. Nectin-4 is a new bio-marker whose use could help refine breast cancer taxonomy and improve patients' follow-up. Nectin-4 emerges as a potential target for breast cancer immunotherapy.