Supernat Anna, Markiewicz Aleksandra, Welnicka-Jaskiewicz Marzena, Seroczynska Barbara, Skokowski Jaroslaw, Sejda Aleksandra, Szade Jolanta, Czapiewski Piotr, Biernat Wojciech, Zaczek Anna
Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland.
Appl Immunohistochem Mol Morphol. 2012 Mar;20(2):103-7. doi: 10.1097/pai.0b013e3182311d82.
Ecto-5'-nucleotidase (CD73) is a membrane-bound enzyme, which catalyzes the conversion of adenosine monophosphate to adenosine. CD73 has been postulated to play an important role in carcinogenesis, as adenosine promotes tumor progression and CD73-expressing cancer cell lines are more aggressive. However, other studies have shown that activated adenosine receptors may also inhibit cell proliferation. This study investigated the clinical significance of CD73 expression in breast cancer. The study group included 136 consecutive stage I-III breast cancer patients treated between 2001 and 2008 at 2 institutions. CD73 expression was examined by immunohistochemistry (IHC) on tissue microarrays, using antihuman mouse monoclonal antibody. Survival curves were generated by the Kaplan-Meier method and compared using the log-rank test. CD73 staining was expressed as the score calculated by multiplying the staining intensity (0=negative, 1=weak, 2=intermediate, 3=strong) and percentage of positive cells (0% to 100%). The median score among all samples was 100. Positive CD73 staining (defined as score equal or higher than 100) occurred in 74% of the cases. No correlation was found between CD73 expression and grading, tumor size, lymph node status, histologic type, estrogen receptor, or progesterone receptor status. Positive CD73 expression strongly correlated with longer disease-free survival (hazard ratio=0.26; 95% confidence interval, 0.1-0.66; P=0.0044) and overall survival (hazard ratio =0.24; 95% confidence interval, 0.07-0.85; P=0.027). Multivariate analysis for disease-free survival revealed correlation with tumor size and CD73 status. Elevated CD73 expression in breast cancer can predict a good prognosis. However, the actual role of CD73 in cancerogenesis remains unclear and requires further analysis.
胞外5'-核苷酸酶（CD73）是一种膜结合酶，可催化单磷酸腺苷转化为腺苷。据推测，CD73在致癌过程中起重要作用，因为腺苷可促进肿瘤进展，且表达CD73的癌细胞系更具侵袭性。然而，其他研究表明，激活的腺苷受体也可能抑制细胞增殖。本研究调查了CD73表达在乳腺癌中的临床意义。研究组包括2001年至2008年期间在2家机构接受治疗的136例连续的I - III期乳腺癌患者。使用抗人鼠单克隆抗体，通过免疫组织化学（IHC）在组织微阵列上检测CD73表达。生存曲线采用Kaplan-Meier法生成，并使用对数秩检验进行比较。CD73染色表示为通过将染色强度（0 =阴性，1 =弱阳性，2 =中等阳性，3 =强阳性）与阳性细胞百分比（0%至100%）相乘计算得出的分数。所有样本的中位分数为100。74%的病例出现CD73阳性染色（定义为分数等于或高于100）。未发现CD73表达与分级、肿瘤大小、淋巴结状态、组织学类型、雌激素受体或孕激素受体状态之间存在相关性。CD73阳性表达与更长的无病生存期（风险比=0.26；95%置信区间，0.1 - 0.66；P = 0.0044）和总生存期（风险比 = 0.24；95%置信区间，0.07 - 0.85；P = 0.027）密切相关。无病生存期的多变量分析显示与肿瘤大小和CD73状态相关。乳腺癌中CD73表达升高可预测良好预后。然而，CD73在癌症发生中的实际作用仍不清楚，需要进一步分析。
