Expression of Abl interactor 1 and its prognostic significance in breast cancer: a tissue-array-based investigation.
Abl interactor 1 (Abi1) is an adaptor protein involved in cell migration. Previous in vitro work suggested that Abi1 is a regulator of breast cancer proliferation, migration, and invasion. In the present study, we explore the expression of Abi1 and its downstream effector phospho-Akt (p-Akt) in a series of breast cancers and correlate their expression with clinicopathological and survival data. Using tissue microarrays, 988 patients with invasive breast carcinoma were evaluated by immunohistochemistry. Statistical correlation was performed to determine associations between Abi1 and p-Akt expression and standard breast clinicopathological factors. The prognostic value of Abi1 and p-Akt for disease-free (DFS) and overall survival (OS) was also evaluated. Abi1 expression was demonstrated in 33.7% (314/933) of invasive carcinomas, while p-Akt was expressed in 46.7% (441/944). There was a significant association between Abi1 and p-Akt expression (P=0.001). Abi1 expression showed significant positive correlation with older age at diagnosis and the Ki67 index. Most importantly, it was demonstrated to be an independent predictor of both DFS and OS (HR = 1.6 and 1.5, P<0.001, respectively). There was no association between p-Akt expression and survival. To the best of our knowledge, this is the first study evaluating Abi1 expression in a large group of breast cancers. Our analysis demonstrated that tumors expressing high levels of Abi1 are significantly associated with early recurrence and worse survival on multivariate analysis. This suggests that Abi1 expression has potential as a molecular marker to refine outcome prediction in breast cancer patients.
Department of Pathology, University of Manitoba, Winnipeg, MB, Canada.
Chunjie
C
Wang
Danh
D
Tran-Thanh
Juan C
JC
Moreno
Thomas R
TR
Cawthorn
Lindsay M
LM
Jacks
Dong-Yu
DY
Wang
David R
DR
McCready
Susan J
SJ
Done
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis* / Q000235:genetics; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D046888:Tissue Array Analysis / Q000379:methods; D015854:Up-Regulation
C513733:ABI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D051057:Proto-Oncogene Proteins c-akt