Eukaryotic initiation factor 4E (eIF4E) and angiogenesis: prognostic markers for breast cancer.
BACKGROUND
The overexpression of eukaryotic translation initiation factor 4E (eIF4E), a key regulator of protein synthesis, is involved in the malignant progression of human breast cancer. This study investigates the relationship between eIF4E and angiogenesis, as well as their prognostic impact in patients with human breast cancer.


METHODS
Immunohistochemical staining was used to determine protein expression of eIF4E, vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and CD105 in a set of 122 formalin-fixed, paraffin-embedded primary breast cancer tissues. Expression of eIF4E in positive cells was characterized by cytoplasmic staining. Evaluation of VEGF and IL-8 in the same tissue established the angiogenic profiles, while CD105 was used as an indicator of microvessel density (MVD).


RESULTS
A significant relationship was found between the level of eIF4E expression and histological grade (P = 0.016). VEGF, IL-8, and MVD were closely related to tumor grade (P = 0.003, P = 0.022, and P < 0.001, respectively) and clinical stage (P = 0.007, P = 0.048, and P < 0.001, respectively). Expression of eIF4E was also significantly correlated with VEGF (P = 0.007), IL-8 (P = 0.007), and MVD (P = 0.006). Patients overexpressing eIF4E had significantly worse overall (P = 0.01) and disease-free survival (P = 0.006). When eIF4E, histological grade, tumor stage, ER, PR, Her-2 status and the levels of VEGF, IL-8, MVD were included in a multivariate Cox regression analysis, eIF4E emerged as an independent prognostic factor for breast cancer (P = 0.001), along with stage (P = 0.005), node status (P = 0.046), and MVD (P = 0.004).


CONCLUSIONS
These results suggest that higher eIF4E expression correlates with both angiogenesis and vascular invasion of cancer cells, and could therefore serve as a useful histological predictor for less favorable outcome in breast cancer patients, as well as represent a potential therapeutic target.
Zhou
Sheng
S
Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. zhou71@163.com
Wang
Guo-Ping
GP
Liu
Cong
C
Zhou
Muxiang
M
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D000071063:Endoglin; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D015993:Life Tables; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D016019:Survival Analysis; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D039561:Eukaryotic Initiation Factor-4E; D016209:Interleukin-8; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A