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.