Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmö Diet and Cancer Study.
Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmö Diet and Cancer Study.
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DOI：
10.1186/1479-5876-9-114
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发表时间：
2011-07-21
影响因子：
7.4
通讯作者：
Jirström K
中科院分区：
文献类型：
--
作者：
Jonsson L;Bergman J;Nodin B;Manjer J;Pontén F;Uhlén M;Jirström K
我们以前曾报道过，RNA和DNA结合蛋白RBM3的表达与乳腺癌和卵巢癌的良好预后有关。在这项研究中，免疫组织化学RBM3表达在恶性黑色素瘤发病病例中的预后价值通过前瞻性人群队列研究进行了评估。截至2008年12月31日，马尔默饮食与癌症研究中登记了264例原发性侵袭性黑色素瘤病例。从226例(85.6%)合适的石蜡包埋肿瘤和31例转移瘤构建的可用病例和组织芯片(TMA)中获得了组织病理学和临床信息。用免疫组织化学方法分析RBM3在TMA和部分面部组织切片上的表达。采用卡方检验和Mann-Whitney U检验比较RBM3的表达及相关临床病理特征。采用Kaplan Meier分析和Cox比例风险模型分析RBM3与无复发生存期(RFS)和总生存期(OS)的关系。在215/226(95.1%)的原发肿瘤和所有转移瘤中可以检测到RBM3。纵向分析显示，16/31(51.6%)的转移瘤不表达RBM3，而在原发灶中，3/215(1.4%)例RBM3不表达，120/215(55.8%)例强表达。RFS(RR=0.50；95%CI=0.27~0.91)和OS(RR=0.36，95%CI=0.20~0.64)与原发肿瘤中核RBM3的高表达显著相关。多因素分析显示，RBM3对OS的有利预后价值仍显著(RR=0.33；95%CI=0.18~0.61)。与之前的体外实验数据一致，我们在这里显示RBM3在转移性黑色素瘤中下调，并且在原发肿瘤中高表达的核RBM3是OS延长的独立标志。RBM3在黑色素瘤患者治疗分层中的潜在应用应在未来的研究中继续进行。
We have previously reported that expression of the RNA- and DNA-binding protein RBM3 is associated with a good prognosis in breast cancer and ovarian cancer. In this study, the prognostic value of immunohistochemical RBM3 expression was assessed in incident cases of malignant melanoma from a prospective population-based cohort study. Until Dec 31st 2008, 264 incident cases of primary invasive melanoma had been registered in the Malmö Diet and Cancer Study. Histopathological and clinical information was obtained for available cases and tissue microarrays (TMAs) constructed from 226 (85.6%) suitable paraffin-embedded tumours and 31 metastases. RBM3 expression was analysed by immunohistochemistry on the TMAs and a subset of full-face sections. Chi-square and Mann-Whitney U tests were used for comparison of RBM3 expression and relevant clinicopathological characteristics. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the relationship between RBM3 and recurrence free survival (RFS) and overall survival (OS). RBM3 could be assessed in 215/226 (95.1%) of primary tumours and all metastases. Longitudinal analysis revealed that 16/31 (51.6%) of metastases lacked RBM3 expression, in contrast to the primary tumours in which RBM3 was absent in 3/215 (1.4%) cases and strongly expressed in 120/215 (55.8%) cases. Strong nuclear RBM3 expression in the primary tumour was significantly associated with favourable clinicopathological parameters; i.e. non-ulcerated tumours, lower depth of invasion, lower Clark level, less advanced clinical stage, low mitotic activity and non-nodular histological type, and a prolonged RFS (RR = 0.50; 95% CI = 0.27-0.91) and OS (RR = 0.36, 95%CI = 0.20-0.64). Multivariate analysis demonstrated that the beneficial prognostic value of RBM3 remained significant for OS (RR = 0.33; 95%CI = 0.18-0.61). In line with previous in vitro data, we here show that RBM3 is down-regulated in metastatic melanoma and high nuclear RBM3 expression in the primary tumour is an independent marker of a prolonged OS. The potential utility of RBM3 in treatment stratification of patients with melanoma should be pursued in future studies.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
45.3
作者：
Gimotty, Phyllis A.;Elder, David E.;Guerry, DuPont
通讯作者：
Guerry, DuPont
影响因子：
6.2
作者：
McKinnon, JG;Yu, XO;Thompson, JF
通讯作者：
Thompson, JF
影响因子：
82.9
作者：
Kononen, J;Bubendorf, L;Kallioniemi, OP
通讯作者：
Kallioniemi, OP
影响因子：
64.8
作者：
Bittner, M;Meitzer, P;Trent, J
通讯作者：
Trent, J