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细胞质到核 maspin 表达的转移与无淋巴结转移结直肠癌的总生存期更短相关。

Shift from cytoplasmic to nuclear maspin expression correlates with shorter overall survival in node-negative colorectal cancer.

机构信息

Institute of Pathology, Klinikum Augsburg, Augsburg 86156, Germany.

出版信息

Hum Pathol. 2010 Jul;41(7):1024-33. doi: 10.1016/j.humpath.2009.10.021. Epub 2010 Mar 23.

DOI:10.1016/j.humpath.2009.10.021
PMID:20334895
Abstract

Maspin has been characterized as a potent tumor suppressor in many in vitro and in vivo studies. In contrast, in stage III colon cancer, an association with shorter overall survival as well as sensitivity to chemotherapy was found for cases with nuclear maspin expression. Because 20% of node-negative colorectal cancer cases show a fatal clinical course, we hypothesized that immunohistochemical maspin expression could be of help to identify higher-risk cases. Therefore, we analyzed survival in a study employing 156 cases of stage I/II colorectal cases. Immunohistochemical cytoplasmic and/or nuclear maspin expression was found in 72% and 48% of the cases, respectively. Significant correlations between cytoplasmic expression and high tumor grade (P < .01) and between nuclear expression and tumor budding (P < .001) were shown. No differences concerning overall survival and immunohistochemical maspin expression were found when the complete collective was analyzed. However, evaluation of the pT3 cases revealed a highly significant worse mean overall survival of cases with a combination of nuclear expression and cytoplasmic loss of maspin compared to cases with the opposite expression pattern nuclear loss and cytoplasmic expression (mean overall survival 40 versus 63 months, respectively; P < .001). The other possible combinations (complete positive and complete negative) showed intermediate mean overall survival times with 54 and 49 months, respectively. Our findings suggest a compartment-dependent function of maspin in colorectal cancer, which can be useful in identifying stage II cases with a higher risk for fatal outcome with a possible benefit from adjuvant chemotherapy.

摘要

Maspin 已被多项体外和体内研究鉴定为一种有效的肿瘤抑制因子。然而,在 III 期结肠癌中,核 maspin 表达与总生存期缩短以及对化疗的敏感性相关。由于 20%的无淋巴结转移结直肠癌病例表现出致命的临床病程,我们假设免疫组织化学 maspin 表达可有助于识别高风险病例。因此,我们分析了 156 例 I/II 期结直肠癌病例的生存情况。免疫组织化学细胞质和/或核 maspin 表达分别在 72%和 48%的病例中发现。细胞质表达与高肿瘤分级(P <.01)之间以及核表达与肿瘤芽生(P <.001)之间存在显著相关性。当完整的病例组被分析时,未发现总生存期与免疫组织化学 maspin 表达之间存在差异。然而,当评估 pT3 病例时,发现核表达和细胞质丢失的 maspin 组合的病例的平均总生存期明显差于相反表达模式的核丢失和细胞质表达的病例(平均总生存期分别为 40 个月和 63 个月;P <.001)。其他可能的组合(完全阳性和完全阴性)的平均总生存期分别为 54 个月和 49 个月。我们的研究结果表明,结直肠癌中 maspin 具有依赖于隔室的功能,这可能有助于识别具有致命结局高风险的 II 期病例,并可能从辅助化疗中获益。

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