Clinical progressive disease (cPD) occurs during neoadjuvant therapy (NAC) in 3 to 5% of breast cancer patients. The expression of epithelial-to-mesenchymal transition (EMT) or ABC transporter-associated genes was shown to be correlated with chemo-resistant phenotype of breast cancer cell lines. In order to reveal clinical implication of EMT and ABC transporter-associated molecules on the acquisition of cPD property, we designed a retrospective histopathological and immunohistochemical case-control study.
From pathology database of patients who received surgical resection, 102 patients with early triple-negative breast cancer (TNBC) were identified: 22 patients suffered cPD during NAC (PD group) and 80 control group patients did not receive NAC (C group), in whom >95% of patients was estimated to be non-PD group if NAC was performed. We immunohistochemically examined the expressions of ABCB1 as a member of ABC transporter and the expressions of Vimentin, TwistNB, E-cadherin, ZEB1 and Snail as EMT-associated markers, and cytoplasmic HMGB1 as immune reaction marker. The chi-square test was used to assess statistically significant differences between the groups.
Histologically, PD group comprised 14 invasive ductal carcinomas (IDCs) (64%) and 8 metaplastic carcinomas (MPCs) (36%). In C group, 59 (74%) were IDCs and 20 (25%) were other types than IDC or MPC, and there was only 1 MPC (1%) (p < 0.001). Cytoplasmic Vimentin was positive in 77% of PD group and the incidence was higher than that in C group (54%) (p =0.0495). Nuclear Twist NB, ZEB1, Snail2 and HMGB1 expression were more frequent in PD group (27, 36, 59 and 86%) than in C group (3, 13, 48 and 51%) (p = 0.0011, 0.0093, 0.0496, 0.0023). Nuclear ABCB1 expression was more frequent in PD group (64%) than in C group (6%) (p <0.001) while cytoplasmic ABCB1 was more frequent in C group (96%) than in PD group (77%) (p = 0.011) .All but one of PD group were positive for either ABCB1, or ZEB1, or Vimentin.
EMT features detected by metaplastic phenotype and Vimentin, ZEB1, Snail2 and HMGB1 expression and increased nuclear localization of ABCB1 could be predictors of cPD during NAC in TNBC.
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All authors have declared no conflicts of interest.