Yuan Yuan, Leszczynska Magdalena, Konstantinovsky Sophya, Tropé Claes G, Reich Reuven, Davidson Ben
Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway.
Diagn Cytopathol. 2011 Aug;39(8):562-6. doi: 10.1002/dc.21424. Epub 2010 Aug 20.
We recently identified overexpression of the NTN4 gene in breast carcinoma effusions compared to primary carcinomas using gene-expression arrays. The objective of this study was to validate this finding at protein level and analyze the clinical role of Netrin-4 in breast carcinoma effusions. We additionally studied Netrin-4 expression and its clinical relevance in Müllerian (ovarian, peritoneal, and tubal) carcinoma effusions. Sections from 82 breast carcinomas (53 effusions and 29 solid tumors) and 57 Müllerian carcinoma effusions were stained for Netrin-4 using immunohistochemistry. Immunoreactivity was scored in carcinoma cells and analyzed for association with clinicopathologic parameters, including survival. In breast carcinoma, expression of Netrin-4 was detected in carcinoma cells in 30/53 (57%) effusions compared to 3/29 (10%) solid tumors (P < 0.001). Netrin-4 was further expressed in 31/57 (54%) Müllerian carcinoma effusions. No association was found between Netrin-4 expression in breast or Müllerian carcinoma effusions and clinicopathologic parameters, including survival. Our data provide validation on protein level of upregulated Netrin-4 expression in breast carcinoma effusions. The frequent expression of Netrin-4 in Müllerian carcinoma effusions suggests a biological role for this molecule in metastases from gynecological malignancies. Netrin-4 expression in effusions does not appear to be a predictor of disease outcome.
我们最近利用基因表达阵列发现，与原发性乳腺癌相比，NTN4基因在乳腺癌积液中过表达。本研究的目的是在蛋白质水平验证这一发现，并分析Netrin-4在乳腺癌积液中的临床作用。我们还研究了Netrin-4在苗勒氏管（卵巢、腹膜和输卵管）癌积液中的表达及其临床相关性。采用免疫组织化学法对82例乳腺癌（53例积液和29例实体瘤）和57例苗勒氏管癌积液的切片进行Netrin-4染色。对癌细胞中的免疫反应性进行评分，并分析其与包括生存在内的临床病理参数的相关性。在乳腺癌中，53例积液中有30例（57%）癌细胞检测到Netrin-4表达，而29例实体瘤中只有3例（10%）检测到（P<0.001）。31/57（54%）的苗勒氏管癌积液中进一步检测到Netrin-4表达。未发现乳腺癌或苗勒氏管癌积液中Netrin-4表达与包括生存在内的临床病理参数之间存在相关性。我们的数据在蛋白质水平上验证了乳腺癌积液中Netrin-4表达上调。Netrin-4在苗勒氏管癌积液中的频繁表达表明该分子在妇科恶性肿瘤转移中具有生物学作用。积液中Netrin-4的表达似乎不是疾病预后的预测指标。
