CD44异构体在HER23+阳性乳腺癌中的表达及其与预后的关系  

Heterogeneous expressions of CD44 variant isoforms in HER23+positive breast cancer and its prognosis

作　　者：唐诗[1] 温珮琦 邓杰华[1] 李凯恒 陈黛诗 TANG Shi;WEN Peiqi;DENG Jiehua;LI Kaiheng;CHEN Daishi(Department of Breast Surgery,Dongguan City Maternal&Child Health Hospital,Dongguan 523057,Guangdong Province,China;Department of Otorhinolaryngology,Shenzhen People’s Hospital(The Second Clinical Medical College,Jinan University),Shenzhen 518020,Guangdong Province,China)

机构地区：[1]东莞市妇幼保健院乳腺科,广东东莞523057 [2]深圳市人民医院(暨南大学第二临床医学院,南方科技大学第一附属医院)耳鼻咽喉科,广东深圳518020

出　　处：《解放军医学院学报》2024年第7期746-752,共7页Academic Journal of Chinese PLA Medical School

基　　金：国家自然科学基金项目(31801160);东莞市社会科技发展重点项目(202050715007202)。

摘　　要：背景跨膜蛋白CD44与癌细胞侵袭和转移行为有密切关系,其异构体CD44v6和CD44v8-10在HER23+阳性乳腺癌中的作用尚不明确。目的分析CD44异构体CD44v6和CD44v8-10在HER23+阳性乳腺癌中的表达及其与预后的关系。方法收集2019年1月—2022年6月就诊于东莞市妇幼保健院乳腺科经术前粗针穿刺活检确诊HER23+,并接受新辅助治疗后行手术切除的乳腺癌患者。应用免疫组织化学(IHC)对乳腺癌标本进行CD44v6和CD44v8-10染色,分析两者与HER2、雌激素受体、孕激素受体等临床病理特征和病理完全缓解(pathologic complete response,pCR)之间的关系。结果86例HER23+阳性乳腺癌患者年龄(46.99±10.01)岁,均为女性。全部患者均表现出CD44异构体异质性表达,其中55例(64.0%)CD44v6高表达,58例(67.4%)CD44v8-10高表达。CD44v6高表达组的ER阳性率(76.4%vs 48.4%,P=0.017)、PR阳性率(78.2%vs 19.4%,P<0.001)和Ki67阳性指数(81.8%vs 61.3%,P=0.043)均高于CD44v6低表达组,差异有统计学意义。CD44v8-10高表达组的PR阳性率(70.7%vs 28.6%,P<0.001)和淋巴结转移发生率(72.4%vs 14.3%,P<0.001)均高于CD44v8-10低表达组,差异有统计学意义。此外,CD44v6低表达组和CD44v8-10低表达组的pCR率均显著高于CD44v6高表达组(54.8%vs 30.9%,P=0.039)和CD44v8-10高表达组(71.4%vs 24.1%,P<0.001),差异有统计学意义。多因素Logistic回归分析显示HER2弥漫3+和CD44v8-10高表达的患者pCR率更低(OR=5.281,95%CI:1.346~20.718,P=0.017;OR=5.062,95%CI:1.232~20.799,P=0.024)。结论CD44异构体与HER23+阳性乳腺癌的恶性特征相关,CD44v8-10可作为HER2弥漫3+预后不良的标志物。Background CD44 variant isoforms are involved in the progression of breast cancer.However,the clinicopathological features and prognostic risk of CD44 variant isoforms(v6 and v8-10)in HER23+positive breast cancer are still unclear.Objective To investigate the expressions and clinical significance of CD44v6 and CD44v8-10 in HER23+positive breast cancer.Methods This study included patients with HER2 IHC3+breast cancer undergoing neoadjuvant treatment and surgery who were diagnosed with core needle biopsy specimens from January 2019 to June 2022 in Dongguan City maternal&Child Health Hospital.Immunohistochemistry(IHC)was used to determine the expressions of CD44v6 and CD44v8-10.The correlations between CD44v6 or CD44v8-10 between HER2,estrogen receptor(ER)and progesterone receptor(PR)status,clinicopathological parameters and pathological complete response(pCR)were analyzed.Results The average age of the 86 cases with HER23+cases was(46.99±10.01)years.All cases showed a heterogeneous expression pattern of the CD44v6 and CD44v8-10,55(64.0%)cases with CD44v6 high expression and 58(67.4%)with CD44v8-10 high expression.Patients with high CD44v6 tumors had a significantly higher ER(76.4%vs 48.4%,P=0.017),PR(78.2%vs 19.4%,P<0.001)and Ki67(81.8%vs 61.3%,P=0.043)rate than those with low CD44v6 tumors.Patients with high CD44v8-10 tumors had a significantly higher PR(70.7%vs 28.6%,P<0.001)and lymph node metastasis(72.4%vs 14.3%,P<0.001)rate than those with low CD44v8-10 tumors.Patients with low CD44v6 expression(54.8%vs 30.9%;P<0.001)or CD44v8-10 expression(71.4%vs 24.1%;P<0.001)showed higher pCR rate than high expressions,respectively.Multivariate analysis showed that patients with HER2 diffuse 3+and CD44v8-10 had lower pCR(OR=5.281,95%CI:1.346-20.718,P=0.017;OR=5.062,95%CI:1.232-20.799,P=0.024,respectively).Conclusion We demonstrate that CD44 isoforms heterogeneity can be associated with the malignant features in HER23+breast cancer.CD44v8-10 can be considered to predict the prognosis of HER2 diffuse 3+breast cancer.

关 键 词：CD44 异构体 HER2 乳腺癌 预后 

分 类 号：R737.9[医药卫生—肿瘤] R392.11[医药卫生—临床医学]