唐诗, 温珮琦, 邓杰华, 李凯恒, 陈黛诗. CD44异构体在HER2 3+ 阳性乳腺癌中的表达及其与预后的关系[J]. 解放军医学院学报, 2024, 45(7): 746-752. DOI: 10.12435/j.issn.2095-5227.2024.056
引用本文: 唐诗, 温珮琦, 邓杰华, 李凯恒, 陈黛诗. CD44异构体在HER2 3+ 阳性乳腺癌中的表达及其与预后的关系[J]. 解放军医学院学报, 2024, 45(7): 746-752. DOI: 10.12435/j.issn.2095-5227.2024.056
TANG Shi, WEN Peiqi, DENG Jiehua, LI Kaiheng, CHEN Daishi. Heterogeneous expressions of CD44 variant isoforms in HER2 3+ positive breast cancer and its prognosis[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2024, 45(7): 746-752. DOI: 10.12435/j.issn.2095-5227.2024.056
Citation: TANG Shi, WEN Peiqi, DENG Jiehua, LI Kaiheng, CHEN Daishi. Heterogeneous expressions of CD44 variant isoforms in HER2 3+ positive breast cancer and its prognosis[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2024, 45(7): 746-752. DOI: 10.12435/j.issn.2095-5227.2024.056

CD44异构体在HER2 3+ 阳性乳腺癌中的表达及其与预后的关系

Heterogeneous expressions of CD44 variant isoforms in HER2 3+ positive breast cancer and its prognosis

  • 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HER2 3+ 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HER2 3+ 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HER2 3+ ,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HER2 3+ 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HER2 3+ 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。

     

    Abstract:
    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 HER2 3 + positive breast cancer are still unclear.
    Objective To investigate the expressions and clinical significance of CD44v6 and CD44v8-10 in HER2 3 + 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 HER2 3 + 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 HER2 3 + breast cancer. CD44v8-10 can be considered to predict the prognosis of HER2 diffuse 3 + breast cancer.

     

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