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