[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: Fenglin Zang, Xiyin Wei, Baocun Sun
• Journal: Zhonghua bing li xue za zhi = Chinese journal of pathology (Zhonghua Bing Li Xue Za Zhi) Vol. 43 Issue 7 Pg. 442-6 (Jul 2014) ISSN: 0529-5807 [Print] China
• PMID: 25327791 (Publication Type: English Abstract, Journal Article)

Chemical References

• Biomarkers, Tumor
• CASP8 and FADD-Like Apoptosis Regulating Protein
• CFLAR protein, human
• Receptor, ErbB-2

Topics

• Aged
• Biomarkers, Tumor (metabolism)
• Breast (metabolism)
• Breast Neoplasms (classification, metabolism, mortality)
• CASP8 and FADD-Like Apoptosis Regulating Protein (metabolism)
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Prognosis
• Receptor, ErbB-2 (metabolism)