title: [Relationship of c-FLIP(L) protein expression with molecular subtyping and clinical prognosis in invasive breast cancer].
abstract: OBJECTIVE
  To investigate the expression of apoptotic regulator c-FLIP(L) in invasive breast carcinoma tissues, and to evaluate its correlation with molecular subtyping and clinical prognosis.
  
  
  METHODS
  Immunohistochemistry using EnVision staining for c-FLIP(L) was performed in 264 cases of invasive breast carcinomas and matched adjacent normal breast tissue samples from January 1996 to December 1999. ER, PR, HER2, Ki-67, CK5/6 and EGFR were evaluated by immunohistochemistry in order to classify the tumors into five molecular subtypes and the difference of c-FLIP(L) expression in these molecular subtypes was also analyzed. The influence of c-FLIP(L) expression on prognosis was evaluated by Kaplan-Meier curves and multi-factor Cox proportional risk model.
  
  
  RESULTS
  High expression of c-FLIP(L) was observed in 84.5% (223/264) of cases of invasive breast carcinomas which were significantly higher than the 45.1% (119/264) of cases in adjacent normal epithelium of breast (χ² = 89.78, P = 0.000). The expression of c-FLIP(L) in luminal B (HER2 positive) and basal-like breast cancers was 78.1% (25/32) and 46.2% (18/39), respectively, with significant difference (P < 0.05). Moreover, the expression of c-FLIP(L) in luminal B (HER2 positive) was higher than in luminal A cancers (P < 0.05), and the expression of c-FLIP(L) in HER2 positive cancers was higher than in basal-like cancers (P < 0.01). C-FLIP(L) showed deep yellow staining in node positive breast cancer with a high-expression rate of 93.1% (134/144); whereas the expression was sporadic and light yellow in node negative breast cancer with a lower high-expressed rate of 72.5% (87/120, P < 0.01). C-FLIP(L) expression had significant influence on disease-free survival time, with c-FLIP(L)-positive patients showing poor prognosis (P < 0.01). Multi-factor Cox proportional risk model analysis showed that expression of c-FLIP(L), lymph nodes status and molecular subtypes were independent prognostic factors for invasive breast carcinomas (P < 0.05).
  
  
  CONCLUSIONS
  C-FLIP(L) is highly expressed in invasive breast carcinomas, and its expression level is closely related to the molecular subtypes and clinical prognosis of breast cancer patients. Thus, c-FLIP(L) could be used as an important tumor marker for personalized cancer therapy and prognostic prediction.
authors.affiliation: Department of Pathology of Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Fenglin
authors.initials: F
authors.lastname: Zang
authors.affiliation: Department of Pathology of Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Xiyin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pathology of Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. E-mail: baocun_sun@126.com.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism* / Q000401:mortality; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; C506386:CFLAR protein, human