Tryfonidis Konstantinos, Kafousi Maria, Perraki Maria, Apostolaki Stella, Agelaki Sofia, Georgoulias Vassilis, Stathopoulos Efstathios, Mavroudis Dimitris
Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
Department of Pathology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
Clin Breast Cancer. 2014 Dec;14(6):442-50. doi: 10.1016/j.clbc.2014.04.001. Epub 2014 Jun 2.
Previous studies showed that molecular detection of CK-19 mRNA in peripheral blood and the mitotic index of primary tumors have prognostic value in early breast cancer. The aim of this study was to assess the association between these variables.
The primary tumors of 223 operable breast cancer patients (92 premenopausal and 131 postmenopausal) were evaluated for the MAI classified as either ≤ 5 per 10, 6 to 10 per 10 and > 10 per 10 or < 10 per 10 and ≥ 10 per 10 mitoses per high power field using a standardized protocol previously reported. Peripheral blood was also collected before and after the end of adjuvant chemotherapy for detection of CK-19 mRNA-positive cells using reverse transcription polymerase chain reaction previously described.
After a median follow-up of 118 months, 75 patients (33.6%) experienced disease relapse and 56 (25.1%) died of breast cancer. MAI was strongly associated with disease-free survival (DFS) and overall survival (OS) (P < .001 for DFS and OS together). Detecting CK-19 mRNA-positive cells in the peripheral blood before but not after adjuvant chemotherapy was associated with marginally worse DFS (P = .055) and OS (P = .059). Cox regression analysis revealed that MAI and CK-19 mRNA-positive cell detection before adjuvant chemotherapy were independent variables associated with decreased DFS (P < .001 and P = .038, respectively) and OS (P < .001 and P = .029, respectively). There was no significant interaction between MAI and detection of CK-19 mRNA-positive cells.
MAI of the primary tumor and detection of CK-19 mRNA-positive cells in the blood before adjuvant chemotherapy in early breast cancer patients are 2 independent prognostic factors associated with clinical outcome.
既往研究表明，外周血中细胞角蛋白19（CK-19）信使核糖核酸（mRNA）的分子检测以及原发性肿瘤的有丝分裂指数对早期乳腺癌具有预后价值。本研究旨在评估这些变量之间的关联。
采用先前报道的标准化方案，对223例可手术乳腺癌患者（92例绝经前和131例绝经后）的原发性肿瘤进行评估，将有丝分裂活性指数（MAI）分类为每10个高倍视野≤5个、6至10个和>10个有丝分裂，或<10个和≥10个有丝分裂。在辅助化疗结束前后还采集外周血，采用先前描述的逆转录聚合酶链反应检测CK-19 mRNA阳性细胞。
中位随访118个月后，75例患者（33.6%）出现疾病复发，56例（25.1%）死于乳腺癌。MAI与无病生存期（DFS）和总生存期（OS）密切相关（DFS和OS合并P<0.001）。在辅助化疗前而非化疗后在外周血中检测到CK-19 mRNA阳性细胞与略差的DFS（P=0.055）和OS（P=0.059）相关。Cox回归分析显示，MAI和辅助化疗前CK-19 mRNA阳性细胞检测是与DFS降低（分别为P<0.001和P=0.038）和OS降低（分别为P<0.001和P=0.029）相关的独立变量。MAI与CK-19 mRNA阳性细胞检测之间无显著交互作用。
早期乳腺癌患者原发性肿瘤的MAI以及辅助化疗前血液中CK-19 mRNA阳性细胞的检测是与临床结局相关的两个独立预后因素。
