title: Eukaryotic translation initiation factor 4E (eIF4E) expression is associated with breast cancer tumor phenotype and predicts survival after anthracycline chemotherapy treatment.
abstract: Abnormal translation of mRNAs frequently occurring during carcinogenesis is among the mechanisms that can affect the expression of proteins involved in tumor development and progression. Eukaryotic initiation factor eIF4E is a key regulator of translation of many cancer-related transcripts and its expression is altered in various cancers and has been associated with worse survival. We determined the eIF4E protein levels using immunohistochemistry (IHC) in 1,233 breast tumors on tissue microarrays. We analyzed the effects of the IHC expression level on tumor characteristics and patient survival, also with stratification by adjuvant chemotherapy treatment. In 1,085 successfully stained tumors, high level of eIF4E protein expression was associated with features of aggressive tumor phenotype, namely grade, estrogen and progesterone receptor negativity, HER2 receptor positivity, and high expression of p53 and Ki67, and with triple negative subtype (p < 0.001). High eIF4E expression was associated with worse breast cancer-specific survival with a hazard ratio (HR) of 1.99 (95 % CI 1.32-3.00, p = 0.0008) and was in a multivariate analysis an independent prognostic factor. High eIF4E expression was associated with worse outcome also after detection of distant metastasis (HR = 1.88, 95 % CI 1.20-2.94, p = 0.0060). In the subgroup analysis the survival effect was strongest among patients treated with anthracycline chemotherapy (HR = 3.34, 95 % CI 1.72-6.48, p = 0.0002), whereas no such effect was seen among patients who had not received anthracycline with significant difference in heterogeneity between the two groups (p = 0.0358). High expression of eIF4E is associated with adverse tumor characteristics and predicts poor breast cancer-specific survival. This effect is emphasized in patients treated with anthracycline chemotherapy. eIF4E as a treatment predictive factor warrants further studies.
authors: Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. Box 700, 00029 Helsinki, Finland. tuomas.heikkinen@helsinki.fi
authors: Tuomas
authors: T
authors: Heikkinen
authors: Taina
authors: T
authors: Korpela
authors: Rainer
authors: R
authors: Fagerholm
authors: Sofia
authors: S
authors: Khan
authors: Kristiina
authors: K
authors: Aittomäki
authors: Päivi
authors: P
authors: Heikkilä
authors: Carl
authors: C
authors: Blomqvist
authors: Olli
authors: O
authors: Carpén
authors: Heli
authors: H
authors: Nevanlinna
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000145:classification / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000737:chemistry* / Q000145:classification / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D039561:Eukaryotic Initiation Factor-4E / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D016612:Paraffin Embedding; D010641:Phenotype; D011379:Prognosis; D014176:Protein Biosynthesis; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D039561:Eukaryotic Initiation Factor-4E; D009363:Neoplasm Proteins; D003561:Cytarabine; D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide