Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer.
Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer.
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DOI：
10.1038/sj.bjc.6603261
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发表时间：
2006-08-07
影响因子：
8.8
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中科院分区：
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本研究旨在探讨蛋白酪氨酸磷酸酶（PTP）PRL-1、PRL-2和PRL-3在乳腺癌中的表达及其临床意义。PRL-PTP mRNA表达检测恶性（n=7）和非恶性（n=7）冷冻保存的乳腺组织样本，以及在8个乳腺癌细胞系通过RT-PCR。应用组织芯片技术（TMA），对135例乳腺导管原位癌和147例浸润性乳腺癌组织中PRL-3蛋白的表达进行半定量分析。在24例淋巴结阳性患者中，我们选择相应的淋巴结转移进行PRL-3表达分析，并检查了浸润性乳腺癌样本的验证集（n=99）。染色结果与临床病理参数和长期随访相关。PRL-3 mRNA在乳腺癌组织中的表达显著高于良性乳腺组织。对于PRL-1和PRL-2表达，未观察到显著差异。TMAs染色显示PRL-3在85.9%的导管原位癌和75.5%的浸润性乳腺癌中表达。生存参数分析显示，与PRL-3阴性乳腺癌相比，PRL-3阳性乳腺癌患者的无病生存期（DFS）较短，特别是PRL-3过表达肿瘤的乳腺癌阳性患者的DFS显著较短（66±7个月（95%CI，52-80）vs 97±9个月（95%CI，79-115）; P=0.032）。此外，我们发现PRL-3在淋巴结转移瘤中的表达频率高于原发肿瘤（91.7% vs 66.7%; P=0.033）。我们的研究结果表明，PRL-3可能作为一种新的乳腺癌预后因素，这可能有助于预测不良疾病的结果。
The aim of this study was to investigate the expression of the protein tyrosine phosphatases (PTP) PRL-1, PRL-2, and PRL-3 in human breast cancer and to evaluate its clinical and prognostic significance. PRL-PTP mRNA expression was examined in malignant (n=7) and nonmalignant (n=7) cryoconserved breast tissue samples as well as in eight breast cancer cell lines by RT–PCR. Furthermore, protein expression of PRL-3 was analysed semiquantitatively by immunohistochemistry in ductal breast carcinoma in situ (n=135) and invasive breast cancer (n=147) by use of tissue microarray technology (TMA). In 24 lymph node-positive patients we selected the corresponding lymph node metastases for analysis of PRL-3 expression, and a validation set (n=99) of invasive breast cancer samples was examined. Staining results were correlated with clinicopathological parameters and long-term follow-up. PRL-3 mRNA expression was significantly higher in malignant compared to benign breast tissue. For PRL-1 and PRL-2 expression no significant differences were observed. Staining of TMAs showed PRL-3 expression in 85.9% ductal carcinoma in situ and 75.5% invasive breast carcinomas. Analysis of survival parameters revealed a shorter disease-free survival (DFS) in patients with PRL-3-positive carcinomas, and in particular a significantly shorter DFS in nodal-positive patients with PRL-3 overexpressing tumours as compared to PRL-3-negative breast carcinomas (66±7 months (95% CI, 52–80) vs 97±9 months (95% CI, 79–115); P=0.032). Moreover, we found a more frequent expression of PRL-3 in lymph node metastases as compared to the primary tumours (91.7 vs 66.7%; P=0.033). Our results suggest that PRL-3 might serve as a novel prognostic factor in breast cancer, which may help to predict an adverse disease outcome.
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