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Prospective study of eukaryotic initiation factor 4E protein elevation and breast cancer outcome.

Abstract：

OBJECTIVE:To validate the authors' initial hypothesis-generating observation that eukaryotic initiation factor 4E (eIF4E) protein elevation predicts a higher cancer recurrence rate in patients with stage 1 to 3 breast cancer. SUMMARY BACKGROUND DATA:Tumor size and nodal status continue to be the two most important independent prognostic markers in breast cancer, despite well-documented limitations. In a previous smaller retrospective study, eIF4E, important in the regulation of protein synthesis of mRNAs with long or complex 5' untranslated regions, appeared promising as an independent predictor of breast cancer recurrence. METHODS:Specimens and clinical data from 191 patients with stage 1 to 3 breast cancer were accrued prospectively. Data collected include stage of disease, tumor grade, age at diagnosis, and menopausal status. Endpoints measured were disease recurrence and cancer-related death. eIF4E protein level was quantified using Western blot analysis. Immunohistochemical staining was used to determine estrogen receptor, progesterone receptor, and HER-2/neu receptor status. Statistical analysis include Cox proportional hazards model, log-rank test, Kaplan-Meier survival curve, Fisher exact test, and t test. RESULTS:Patients were divided into three groups based on tertile distribution of eIF4E: low, defined as less than 7.5-fold elevation (n = 64); intermediate, defined as 7.5- to 14-fold elevation (n = 61); and high, defined as more than 14-fold elevation (n = 66). The relative risk for cancer recurrence with intermediate elevation was 4.1 times that of patients with low elevation. For patients with high elevation, the relative risk for recurrence was higher, at 7.2 times that of the low group. The relative risk for cancer-related death for high elevation was 7.3 times that of patients with low eIF4E. Using multivariate analysis, high eIF4E remained an independent predictor of cancer recurrence after adjusting for tumor size, tumor grade, nodal disease, estrogen receptor status, progesterone receptor status, and menopausal status. CONCLUSIONS:High eIF4E is an independent predictor of cancer recurrence in patients with stage 1 to 3 breast cancer. The relative risk for cancer recurrence increases with eIF4E protein elevation. High eIF4E elevation is also associated with an increased relative risk for cancer-related death.

journal_name

Ann Surg

journal_title

Annals of surgery

authors

Li BD,Gruner JS,Abreo F,Johnson LW,Yu H,Nawas S,McDonald JC,DeBenedetti A

doi

10.1097/00000658-200205000-00016

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

732-8; discussion 738-9

issue

eissn

0003-4932

issn

1528-1140

journal_volume

235

pub_type

杂志文章

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Prospective study of eukaryotic initiation factor 4E protein elevation and breast cancer outcome.