Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden.
Acta Oncol. 2012 Mar;51(3):386-93. doi: 10.3109/0284186X.2011.631576. Epub 2011 Nov 9.
Expression of the peptide hormones ghrelin and obestatin has previously been demonstrated in human mammary glands. However, the clinical implications of the expression of these peptides in breast cancer are unclear. The aim of this study was to investigate the potential clinical value of ghrelin and obestatin as breast cancer biomarkers.
A tissue microarray containing breast cancer specimens from 144 patients was immunostained with antibodies directed towards ghrelin and obestatin. Using varying cut-offs, the expression of the two peptides was evaluated and correlated to previously known prognostic factors in breast cancer and to the outcome. Cox regression analysis was used to assess whether these markers may predict survival of breast cancer patients.
Moderate to strong immunoreactivity for ghrelin and obestatin was observed in 71.5% and 77.1% of the cases, respectively. Ghrelin and obestatin expression was significantly but weakly correlated to low histological grade, estrogen receptor positivity, small tumor size and low proliferation. Only ghrelin expression was significantly correlated to better recurrence-free and breast cancer-specific survival (HR = 0.3-0.4, p = 0.02-0.05) in both uni- and multivariate analyses. The optimal cut-off was any ghrelin expression versus none. Reproducibility between the two readers was very good for both stainings with kappa values of 0.94-1.00.
Patients with tumors expressing ghrelin had 2.5-3 times lower risk for recurrence or breast cancer death than those lacking ghrelin expression. Ghrelin expression is easily assessable with high reproducibility using immunohistochemistry. Further investigations are needed to establish the clinical significance of ghrelin as a biomarker in breast cancer.
先前已经证实，肽激素 ghrelin 和 obestatin 在人乳腺中有表达。然而，这些肽在乳腺癌中的表达的临床意义尚不清楚。本研究旨在探究 ghrelin 和 obestatin 作为乳腺癌生物标志物的潜在临床价值。
采用针对 ghrelin 和 obestatin 的抗体对包含 144 例患者的乳腺癌标本组织微阵列进行免疫染色。通过使用不同的截断值，评估两种肽的表达情况，并将其与乳腺癌的已知预后因素以及结局进行相关性分析。采用 Cox 回归分析来评估这些标志物是否可以预测乳腺癌患者的生存情况。
ghrelin 和 obestatin 的中度至强免疫反应性分别在 71.5%和 77.1%的病例中观察到。ghrelin 和 obestatin 的表达与低组织学分级、雌激素受体阳性、肿瘤体积小和增殖低显著但微弱相关。仅 ghrelin 的表达与更好的无复发生存和乳腺癌特异性生存显著相关（HR=0.3-0.4，p=0.02-0.05），无论是在单因素还是多因素分析中。最佳截断值是任何 ghrelin 表达与无 ghrelin 表达。两种染色的两位读者之间的重复性非常好，kappa 值为 0.94-1.00。
表达 ghrelin 的肿瘤患者比缺乏 ghrelin 表达的肿瘤患者复发或乳腺癌死亡的风险低 2.5-3 倍。ghrelin 表达可以使用免疫组织化学进行评估，具有较高的重复性。需要进一步的研究来确定 ghrelin 作为乳腺癌生物标志物的临床意义。
