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Loss of the adhesion molecule CEACAM1 is associated with early biochemical recurrence in TMPRSS2:ERG fusion-positive prostate cancers.
International Journal of Cancer ( IF 5.7 ) Pub Date : 2020-03-09 , DOI: 10.1002/ijc.32957
Andreas M Luebke 1 , Wiebke Ricken 1 , Martina Kluth 1 , Claudia Hube-Magg 1 , Cornelia Schroeder 2 , Franziska Büscheck 1 , Katharina Möller 1 , David Dum 1 , Doris Höflmayer 1 , Sören Weidemann 1 , Christoph Fraune 1 , Andrea Hinsch 1 , Corinna Wittmer 1 , Thorsten Schlomm 3 , Hartwig Huland 4 , Hans Heinzer 4 , Markus Graefen 4 , Alexander Haese 4 , Sarah Minner 1 , Ronald Simon 1 , Guido Sauter 1 , Waldemar Wilczak 1 , Jan Meiners 2
Affiliation  

Altered expression of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been linked to adverse tumor features in various cancer types. To better understand the role of CEACAM1 in prostate cancer, we analyzed a tissue microarray containing tumor spots from 17,747 prostate cancer patients by means of immunohistochemistry. Normal prostate glands showed intense membranous CEACAM1 positivity. Immunostaining was interpretable in 13,625 cancers and was considered high in 28%, low in 43% and absent in 29% of tumors. Low and lost CEACAM1 expression was strongly linked to adverse tumor features including high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, positive surgical margin, a high number of genomic deletions and early biochemical recurrence (p < 0.0001 each). Subset analysis of molecularly defined cancer subsets revealed that these associations were strongest in V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-positive cancers and that CEACAM1 loss was prognostic even in tumors harboring genomic deletions of the phosphatase and tensin homolog tumor suppressor (p < 0.0001). Multivariate analysis suggested that CEACAM1 analysis can provide independent prognostic information beyond established prognosis parameters at the stage of the initial biopsy when therapy decisions must be taken. In conclusion, loss of CEACAM1 expression predicts poor prognosis in prostate cancer and might provide clinically useful prognostic information particularly in cancers harboring the TMPRSS2:ERG fusion.

中文翻译:

粘附分子CEACAM1的丧失与TMPRSS2:ERG融合阳性前列腺癌的早期生化复发有关。

癌胚抗原相关细胞粘附分子1(CEACAM1)的表达改变与多种癌症类型的不良肿瘤特征有关。为了更好地了解CEACAM1在前列腺癌中的作用,我们通过免疫组织化学分析了包含来自17,747例前列腺癌患者的肿瘤斑的组织微阵列。正常前列腺显示强烈的膜CEACAM1阳性。免疫染色在13625种癌症中得到了解释,被认为高的占28%,低的占43%,而无肿瘤的占29%。CEACAM1表达的低下和丧失与不良的肿瘤特征密切相关,这些特征包括高经典和定量的格里森分级,淋巴结转移,肿瘤晚期,手术切缘阳性,大量基因组缺失和早期生化复发(每个p <0.0001)。分子定义的癌症子集的亚组分析显示,这些关联在V型禽类成纤维细胞病毒E26癌基因同源物(ERG)融合阳性癌症中最强,即使在携带磷酸酶和肌张力蛋白同源物抑癌基因组缺失的肿瘤中,CEACAM1的丢失也可预后。 (p <0.0001)。多变量分析表明,在必须采取治疗决策的初始活检阶段,CEACAM1分析可提供超出既定预后参数的独立预后信息。总之,CEACAM1表达的丧失预示着前列腺癌的不良预后,并且可能提供临床有用的预后信息,尤其是在携带TMPRSS2:ERG融合蛋白的癌症中。
更新日期:2020-03-09
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