Gustbée Emma, Tryggvadottir Helga, Markkula Andrea, Simonsson Maria, Nodin Björn, Jirström Karin, Rose Carsten, Ingvar Christian, Borgquist Signe, Jernström Helena
Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden.
Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden ; Department of Oncology, Skåne University Hospital, Lund, Sweden.
BMC Clin Pathol. 2015 May 20;15:8. doi: 10.1186/s12907-015-0008-2. eCollection 2015.
The mevalonate pathway synthetizes cholesterol, steroid hormones, and non-steriod isoprenoids necessary for cell survival. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme of the mevalonate pathway and the target for statin treatment. HMGCR expression in breast tumors has recently been proposed to hold prognostic and treatment-predictive information. This study aimed to investigate whether HMGCR expression in breast cancer patients was associated with patient and tumor characteristics and disease-free survival (DFS).
A population-based cohort of primary breast cancer patients in Lund, Sweden was assembled between October 2002 and June 2012 enrolling 1,116 patients. Tumor tissue microarrays were constructed and stained with a polyclonal HMGCR antibody (Cat. No HPA008338, Atlas Antibodies AB, Stockholm, Sweden, diluted 1:100) to assess the HMGCR expression in tumor tissue from 885 patients. HMGCR expression was analyzed in relation to patient- and tumor characteristics and disease-free survival (DFS) with last follow-up June 30(th) 2014.
Moderate/strong HMGCR expression was associated with less axillary lymph node involvement, lower histological grade, estrogen and progesterone receptor positivity, HER2 negativity, and older patient age at diagnosis compared to weak or no HMGCR expression. Patients were followed for up to 11 years. The median follow-up time was 5.0 years for the 739 patients who were alive and still at risk at the last follow-up. HMGCR expression was not associated with DFS.
In this study, HMGCR expression was associated with less aggressive tumor characteristics. However, no association between HMGCR expression and DFS was observed. Longer follow-up may be needed to evaluate HMGCR as prognostic or predictive marker in breast cancer.
甲羟戊酸途径合成细胞存活所必需的胆固醇、类固醇激素和非类固醇类异戊二烯。3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）是甲羟戊酸途径的限速酶，也是他汀类药物治疗的靶点。最近有人提出，乳腺肿瘤中的HMGCR表达具有预后和治疗预测信息。本研究旨在调查乳腺癌患者的HMGCR表达是否与患者及肿瘤特征以及无病生存期（DFS）相关。
2002年10月至2012年6月期间，在瑞典隆德组建了一个基于人群的原发性乳腺癌患者队列，共纳入1116例患者。构建肿瘤组织微阵列，并用多克隆HMGCR抗体（货号HPA008338，瑞典斯德哥尔摩Atlas Antibodies AB公司，稀释比例1:100）进行染色，以评估885例患者肿瘤组织中的HMGCR表达。分析HMGCR表达与患者及肿瘤特征以及无病生存期（DFS）的关系，最后一次随访时间为2014年6月30日。
与HMGCR表达较弱或无表达相比，中度/强HMGCR表达与腋窝淋巴结受累较少、组织学分级较低、雌激素和孕激素受体阳性、HER2阴性以及诊断时患者年龄较大相关。对患者进行了长达11年的随访。在最后一次随访时仍存活且有风险的739例患者中，中位随访时间为5.0年。HMGCR表达与DFS无关。
在本研究中，HMGCR表达与侵袭性较小的肿瘤特征相关。然而，未观察到HMGCR表达与DFS之间的关联。可能需要更长时间的随访来评估HMGCR作为乳腺癌预后或预测标志物的价值。
