Molecular alterations in key-regulator genes among patients with T4 breast carcinoma.
Molecular alterations in key-regulator genes among patients with T4 breast carcinoma.
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DOI：
10.1186/1471-2407-10-458
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发表时间：
2010-08-24
期刊：
影响因子：
3.8
通讯作者：
Palmieri G
中科院分区：
文献类型：
--
作者：
Massidda B;Sini M;Budroni M;Atzori F;Deidda M;Pusceddu V;Perra M;Sirigu P;Cossu A;Palomba G;Ionta M;Palmieri G
被诊断为T4乳腺癌的患者的预后因素被广泛期待。我们在此评估了一组经过长时间随访的T4乳腺癌患者中肿瘤发生相关分子改变的临床作用。1992年至2001年，在撒丁岛连续招募了53例T4乳腺癌患者，观察时间中位数为125个月。存档石蜡包埋的组织切片用于免疫组织化学（IHC）和荧光原位杂交（FISH）分析，以评估生存素，p53和pERK 1 -2蛋白的表达水平以及CyclinD 1和h-prune基因扩增的变化。采用Kaplan-Meier和考克斯回归方法进行生存评估和统计学分析。总的来说，pERK 1 -2（p = 0.027）和生存素（p = 0.008）蛋白表达增加以及h-prune基因扩增（p = 0.045）的患者与这些改变阴性的患者相比，总体生存率显著降低。多变量分析后，原发性肿瘤的原发性化疗和生存素过度表达的病理反应的主要参数作为一个独立的预后因素在我们的系列的作用。虽然是回顾性的，但我们的研究确定了一些对T4乳腺癌患者治疗反应或预后预测有显著影响的分子参数。需要进一步的大型前瞻性研究，以验证这些标记物用于这些患者的管理。
Prognostic factors in patients who are diagnosed with T4 breast carcinomas are widely awaited. We here evaluated the clinical role of some molecular alterations involved in tumorigenesis in a well-characterized cohort of T4 breast cancer patients with a long follow-up period. A consecutive series of 53 patients with T4 breast carcinoma was enrolled between 1992 and 2001 in Sardinia, and observed up for a median of 125 months. Archival paraffin-embedded tissue sections were used for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses, in order to assess alterations in expression levels of survivin, p53, and pERK1-2 proteins as well as in amplification of CyclinD1 and h-prune genes. The Kaplan-Meier and Cox regression methods were used for survival assessment and statistical analysis. Overall, patients carrying increased expression of pERK1-2 (p = 0.027) and survivin (p = 0.008) proteins as well as amplification of h-prune gene (p = 0.045) presented a statistically-significant poorer overall survival in comparison with cases found negative for such alterations. After multivariate analysis, the pathological response to primary chemotherapy and the survivin overexpression in primary carcinoma represented the main parameters with a role as independent prognostic factors in our series. Although retrospective, our study identified some molecular parameters with a significant impact on prediction of the response to therapy or prognosis among T4 breast cancer patients. Further large prospective studies are needed in order to validate the use of such markers for the management of these patients.
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