The Clinicopathologic Significance Of CD44⁺/CD24^-/low And CD24⁺ Tumor Cells In Invasive Micropapillary Carcinoma Of The Breast

Objective:Breast cancer cells with a CD44⁺/CD24^-/lowphenotype have been suggested to have tumor-initiating properties with stem cell-like invasive features.It is unclear whether their prevalence associates with clinicopathologic features of Invasive Micropapillary Carcinoma(IMPC) of the Breast,an unusal subtype of breast cancer with a high incidence of lymph node metastasis and poor prognosis.Methods:This study included 82 cases of IMPC and 80 cases of invasive ductal carcinoma, not otherwise specified(IDC-NOS),both without chemotherapy and radiotherapy before surgery.CD44 and CD24 expression was determined by double-staining immunohistochemistry in paraffin embedded tissue from each case.Results:(1) Compared with the control group of IDC-NOS,IMPC were larger in size (t＝3.000,p＝0.003,table 1),higher staged(Z=-4.467,P=0.000),had a higher lymph node metastasis rate(Z=-5.379,P=0.000,table 1) with more nodes involved per case(10.85 in IMPC versus 5.11 in IDC,t=3.750,P?0.000),and exhibited increased lymphovascular invasion(Z＝-7.310,P＝0.000 ) and extranodal extension(Z=-2.526,P≠0.012).(2) The prevalence of CD44⁺/CD24^{-/ low} tumor cells was higher in IMPC than in IDC- NOS(48.8%versus 31.3%,P=0.023).(3) The CD44⁺/CD24 ^/low tumor cells was also detected in adjacent stroma surrounding the micropapillary structure in 53.7%of IMPC,but scarcely in the stroma of IDC.These tumor cells in stroma of IMPC showed positive Vimentin and a-SMA,and negative E-Cadherin staining by immunohistochemistry.(4) The CD44⁺/CD24^-/low tumor cells in micropapillary structure of IMPC was associated with that in stroma(P=0.002),moreover,they were both associated with lymphovascular invasion and extranodal extension respectively(P＜0.05).(5) The proportion of CD24⁺ tumor cells was also higher in IMPC than IDC-NOS (79.3%versus 60.0%,P=0.008),and the CD24⁺ tumor cells was associated with lymph node metastasis in IMPC(P=0.000). (1) IMPC had a higher lymph node metastasis rate with more nodes involved per case and poor prognosis.(2) The percentage of IMPC components in the whole tumor was not significantly associated with lymph node metastasis rate or the number of positive lymph nodes.(3) In IMPC,tumor size and histological grade are closely related to the extent of lymph nodes involved,(4) The increased proportion of CD44⁺/CD24^-/low and CD24⁺ tumor cells and the EMT(epithelial-mesenchymal transition) may play an important role in aggressiveness and higher metastatic risk of IMPC of the Breast.