Cofilin Expression in Breast Carcinoma with Hormone Receptor-Positive: Prognostic Significance
FI Aranda, J Segui, L Sanchez-Tejada, M Niveiro, J Laforga, C Alenda, M Planelles, G Peiro. Universitary General Hospital, Alicante, Spain; General Hospital, Denia, Alicante, Spain
Background: Cofilin is a protein required to cellular motility and regulation of actin polymerization. The cofilin pathway has been implicated in tumor cell invasion and metastasis. Overexpression has been demonstrated in cell lines of lung, pancreatic, glioblastoma and breast tumors. However, several studies have found cofilin downregulated in hepatocellular carcinoma (HCC) cells with high metastatic potential. The aim of the current study was to investigate the expression and the prognostic significance of cofilin in a series of breast carcinoma (BC) with positive hormone receptor (HR) status.
Design: A total of 177 cases of BC with HR-positive/Her2-negative with lymphadenectomy and without neoadjuvant treatment were retrieved. Median clinical follow-up was 55 months (range 11 to 165 months). Age ranged from 42 to 88 years (median 61 years). Histologic grade (HG) was assessed according to the Nottingham criteria. Immunohistochemical (IHC) staining was performed in whole sections for Bcl2 (cut-off 50%), ER (cut-off 10%), PgR (cut-off 10%), Ki67 (cut-off 20%), p53 (cut-off 20%) and Her2 (2+ and <30% 3+ confirmed by FISH). Further IHC for cofilin (cut-off score 50; range 0-300), CK5/6 (cut-off 10%) and EGFR (cut-off 10%) was performed on tissue microarrays. Significant associations were identified using Chi-square and Fisher's exact test. Actuarial survival was calculated by the Kaplan-Meier method (log rank test). A p-value <0.05 was considered significant.
Results: Increased cofilin expression was observed in 31% of tumors, low Bcl2 in 27%, high Ki67 in 21%; CK5/6 was positive in 12%, p53 in 4% and EGFR in 0,6%. Tumors with cofilin overexpression showed lower HG (p=0.03) and positivity for Bcl2 as a trend (p=0.06). Poorer overall survival was seen for patients with larger tumors (>20 mm) (p=0.03), of G3 (p=0.05), positive lymph nodes (p=0.02) and low Bcl2 (p=0.01). In contrast, cofilin overexpression was strongly associated with a better outcome (100% versus 87 % in negative cases; p=0.0007).
Conclusions: Our findings in a series of patients with BC and HR-positive status show that cofilin expression is associated with good prognostic factors, such as low grade tumors and Bcl2 overexpression as well as with longer patients' survival. Therefore, cofilin is a favourable prognostic factor, in contrast to previous reported data in cellular assays. Supported by grant FIS PI061488.
Monday, March 9, 2009 1:00 PM
Poster Session II # 49, Monday Afternoon