title: High expression of LMTK3 is an independent factor indicating a poor prognosis in estrogen receptor α-positive breast cancer patients.
abstract: OBJECTIVE
  Over 70% of breast cancers are estrogen receptor alpha-positive, and endocrine therapy targeting estrogen action decreases mortality from breast cancer. Recently, a novel protein kinase that regulates estrogen receptor alpha activity, lemur tyrosine kinase-3, has been identified. In this study, we investigated whether messenger RNA expression and polymorphisms of the gene encoding the kinase, LMTK3, are associated with prognosis in breast cancer patients during long-term follow-up.
  
  
  METHODS
  First, we investigated the relationship between messenger RNA expression of LMTK3 and patient outcome in 219 breast cancers. The effects of several variables on survival were tested by Cox proportional hazards regression analysis. Next, we performed LMTK3 genotyping in 471 breast cancers to clarify the prognostic role of these polymorphisms.
  
  
  RESULTS
  Our data showed that LMTK3 expression level was not associated with prognosis in all patients. We then analyzed the impact of LMTK3 mRNA expression on the prognosis of breast cancer according to estrogen receptor alpha status. Both disease-free survival and overall survival were significantly shorter in estrogen receptor alpha-positive patients with high LMTK3 expression receiving adjuvant endocrine therapy than in those patients with low LMTK3 expression. Multivariate Cox regression analysis revealed that high LMTK3 expression was an independent poor prognostic factor in estrogen receptor alpha-positive breast cancer patients. We did not find any correlation between LMTK3 genotypes and prognosis of breast cancer patients in our series.
  
  
  CONCLUSIONS
  Our results show that high expression of LMTK3 is an independent prognostic factor in estrogen receptor alpha-positive breast cancer patients receiving adjuvant endocrine therapy.
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya Division of Diagnostic Pathology, Nagoya City East Medical Center, Nagoya, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Yoshimoto
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hato
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya toyamat-ncu@umin.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyama
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human; C508053:ERBB2 protein, human; C560359:LMTK3 protein, human
keywords: LMTK3; breast cancer; polymorphism