Abstract P5-08-12: Histopathological and immunohistochemical findings for epithelial-to-mesenchymal transition were associated with clinical progressive disease of triple-negative breast cancers during neoadjuvant chemotherapy
Authors: Tanabe Y , Tsuda H , Yamamoto H , Kodaira M , Yunokawa M , Yonemori K , Shimizu C , Tamura K , Kinoshita T , Fujiwara Y 
Published: August 2014

Background: Clinical progressive disease (cPD) occurs during neoadjuvant therapy (NAC) in 3 to 5% of breast cancer patients. By gene expression profiling analyses using DNA microarray, the expression of epithelial-to-mesenchymal transition (EMT)-associated genes were shown to be correlated with chemoresistant phenotype of breast cancer cell lines. In order to reveal clinical implication of EMT-associated molecules on the acquisition of cPD property, we designed a retrospective histopathilogical and immunohistochemical case-control study. Patients and Methods: From pathology database of patients who received surgical resection, 86 patients with early triple-negative breast cancer (TNBC) were identified: 23 patients suffered cPD during NAC (PD group) and 63 control group patients did not receive NAC (C group), in whom &gt;95% of patients was estimated to be non-PD group if NAC was performed. For these 86 cases, histopathological classification was performed and negativity of hormone receptors and HER2 was confirmed. As EMT markers, we immunohistochemically examined the expressions of vimentin, Twist, Twist NB and Snail. The chi-square test was used to assess statistically significant differences between the groups.Results: Histologically, PD group comprised 12 invasive ductal carcinomas (IDCs) (52%) and 11 metaplastic carcinomas (MPCs) (48%), and they all were nuclear grade 3. In C group, 52 (83%) were IDCs and 10 (16%) were histological types other than IDC or MPC, and there was only 1 MPC (1%) (p = 4.31E-08). Nuclear grade was 1, 2, and 3 in 1, 9, and 53, respectively. Vimentin was positive in cytoplasm of 74% of PD group and the incidence was higher than that in C group (49%) (p = 0.016). Cytoplasmic twist-2 and cytoplasmic and nuclear Snail expressions were detected almost equally between PD group and C group. Cytoplasmic Twist NB expression was more frequent in PD group (26%) than in C group (1.6%) (p = 0.0002). In PD group, a total of 17 cases comprising 9 MPCs and 8 IDCs, were positive for vimentin. In these 17 vimentin-positive cases, 14 were stable disease or partial response with an anthracyclin-containing regimen while all 16 patients receiving a taxane-containing regimen became cPD during the taxane-containing regimen.

Patient characteristics PD group (N = 23)Control group(N = 63)Age median (range)42(25-62)55(25-77)Clinical stage:I/II/III0/11/127/44/12Diagnosi at operation:IDC/MPC or MPC containing/others12/11/052/1/10Nuclear grade:1/2/30/0/231/9/53Tumor size at diagnosis4.8(2-14)2.8(1.2-12.0)Neoadjuvant chemoterapy regimen  Anthracyclin containing:AC/CEF11/12-Taxane: paclitaxel/docetaxel20/2-

Conclusion: EMT features detected by metaplastic phenotype and cytoplasmic vimentin expression could be predictors for cPD during NAC for TNBC. The tumors of these phenotypes were likely to be resistant to a taxane-containing regimen.

Immunohistochemical profilingantibodyPD group (N = 23)Control group (N = 63)p-valueVimentin(cytoplasm)17 (74%)31 (49%)0.0411Twist-2(cytoplasm)21(91%)59 (94%)0.7849Snail-2(cytoplasm)12 (52%)38 (60%)0.5548Snail-2(nucleus)14 (61%)34 (54%)0.4677Twist NB(cyroplasm)6 (26%)1 (1.6%)0.0002

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-12.