title: Predictive value of CD44 and CD24 for prognosis and chemotherapy response in invasive breast ductal carcinoma.
abstract: OBJECTIVE
  Cells with unique phenotypes and stem cell-like properties have been found to exist in breast cancer. The aim of the present study was to study the relationship of CD24, CD44, CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor phenotypes' with clinico-pathological features, chemotherapy response and with prognosis.
  
  
  METHODS
  The study included paraffin-embedded tissues of 140 primary and secondary invasive ductal carcinoma samples. All the patients received routine chemotherapy. Expression of CD24, CD44, ER, PR, and Her2 were assayed immunohistochemically. We applied double-staining immunohistochemistry for the detection of CD44(+)/CD24(-/low), CD44(+)/CD24 (+), CD44(-)/CD24(-) and CD44(-)/CD24(+) cells. The association between the proportions of CD44(+)/CD24(-/low) and CD44(-)/CD24(+) and clinicopathological features, chemotherapy response and with prognosis of these patients was evaluated.
  
  
  RESULTS
  CD24 expression was not significantly associated with tumor characteristics, but was significantly associated with poor prognostic variables including ER-, PR-, HER2(+) and triple negative (TN) phenotype; There was no association of CD44 with nodal status, age or HER2 expression. In the correlation analysis, CD24 expression was positively associated with chemotherapy response (P = 0.018), however, CD44 expression was not associated with pathological response to chemotherapy When both markers are considered, the CD44(+)/CD24(-) phenotype had the poor prognosis. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement, recurrent or metastatic tumors and ER/PR status. High CD44(+)/CD24(-) phenotype had poor response to chemotherapy. The median disease-free survival (DFS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 19.8 ± 2.6 months and 31.7 ± 4.2 months, and the median overall survival (OS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 33.5 ± 2.8 months and 51.4 ± 3.9 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44(+)/CD24(-/low) tumor cells was strongly correlated with DFS and OS. However, the CD44(-)/CD24(+), CD44(+)/CD24(+), CD44(-)/CD24 (-) phenotype had no relation with prognosis.
  
  
  CONCLUSIONS
  There was significant correlation between CD44(+)/CD24(-/low) tumor cell prevalence and tumor metastasis, prognosis and chemotherapy response. The CD44(+)/CD24(-) phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.
authors.affiliation: Department of Laboratory, Women and Children's Hospital of Qingdao Qingdao, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Laboratory, Women and Children's Hospital of Qingdao Qingdao, China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Laboratory, Women and Children's Hospital of Qingdao Qingdao, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Laboratory, Women and Children's Hospital of Qingdao Qingdao, China.
authors.forename: Chundong
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University Qingdao, China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D051927:CD24 Antigen / Q000032:analysis*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000276:immunology* / Q000556:secondary / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002648:Child; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors
keywords: Breast cancer; CD24; CD44; chemotherapy; prognosis