目的探讨黏着斑激酶(FAK)及磷酸化的丝氨酸/苏氨酸蛋白激酶(p-AKT)在乳腺癌组织中的表达情况及临床价值。方法收集从1997至2008年于我院行乳腺癌根治手术的271例有完整存档蜡块标本,采用组织微阵列芯片和免疫组化SP法检测FAK和p-AKT在乳腺癌组织中的表达,并对两者的表达情况及其与乳腺癌临床病理因素和患者生存情况的关系进行分析。结果FAK、p-AKT的高表达率分别为53.9%(146/271)、36.2%(98/271),两者的表达水平呈正相关(r=0.397,P〈0.01)。FAK/pAKT同时均高表达的比率为29.2%(79/271)。FAK高表达与孕激素受体(PR)呈负相关(P=0.046),pAKT高表达与组织学分级(P=0.024)、淋巴结转移(P=0.016)呈正相关,FAK与pAKT共同高表达的患者更倾向于出现淋巴结转移、骨/软组织转移(P=0.019,P=0.022)。FAK高表达人群中,p-AKT高表达者的总生存期(OS)明显短于低表达者(P=0.047)。单独分析FAK,72.p—AKT表达与总体人群预后无关,将两者联合分析后,FAK/pAKT均高表达患者的Os明显缩短(P=0.027)。亚组分析显示:HER2阳性患者,FAK/pAKT高表达者的Os缩短(P=0.015),FAK/pAKT高表达是HER2阳性乳腺癌的独立预后因素(HR=3.352,P=0.021)。结论在乳腺癌组织中FAK和p-AKT两者密切相关,FAK/pAKT联合检测能够预测乳腺癌患者的预后,并能够成为HER2阳性乳腺癌的独立预后指标。
Objective To explore the expression prognostic value of FAK combined with pAKT in breast cancer patients. Methods Data from a cohort of 271 invasive breast cancer patients underwent radical operation in The First Hospital, China Medical University from 1997 to 2008, was col- lected. FAK and pAKT was validated by IHC in tissue microarrays and statistically assessed for relationship with chnicopathological factors and prog- nosis. Results The high expression rate of FAK was 53.9% ( 146/271 ), and pAKT was 36.2% (98/271 ) in breast cancer tissues. There was positive correlation between FAK and pAKT (r = 0.397, P 〈 0.01 ).High expression of FAK was related to PR state (P = 0.046), high expression of pAKT was related to histological grade (P = 0.024) and lymph node metastasis (P = 0.016) , and high co-expression of FAK and pAKT was related to lymph node metastasis (P = 0.019 ) and bone/soft tissue metastasis ( P = 0.022 ). High expression of FAK, lower expression of pAKT has better prog- nosis than its higher expression. There was no significant difference of the disease -free survival (DFS) or overall survival ( OS ) between breast cancer patients with/without FAK or pAKT expression. High expression of FAK/pAKT showed worse OS (P = 0.027) in whole patient. HER2 positive subgroup analysis showed that FAK/pAKT negative patients has significantly better OS than positive group (P = 0.015 ), and multivariate Cox proportion- al hazard regression analysis showed that FAK/pAKT is mortahty of independent prognostic factor (HR=3.352, P = 0.021 ). Conclusion There was closely relationship between FAK and pAKT. High co-expression of FAK and pAKT can predict OS of breast cancer patients, which can be used as the mortality of independent prognostic factor of HER2 positive breast cancer patients.