Abstract
Background and AimWe investigated the prognostic importance of dickkopf-1(DKK1) and beta-catenin expression in triple negative breast cancers.MethodsThe expression of DKK1 and beta-catenin was evaluated in breast cell lines using RT-PCR and western blot. Immunohistochemistry was used to characterize the expression pattern of DKK1 and beta-catenin in 85 triple negative breast cancers and prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression modeling.ResultsThe expression of DKK1 was confirmed in hormone-resistant breast cell lines MDA-MB-231, MDA-MB-231-HM and MDA-MB-435. Expression of DKK1 in triple negative breast cancers correlated with cytoplasmic/nuclear beta-catenin (p = 0.000). Elevated expression of DKK1 and cytoplasmic/nuclear beta-catenin in triple negative cancers indicate poor outcome of patients. DKK1 was also a prognostic factor for patients with earlier stage or no lymph node metastasis.ConclusionDKK1 together with beta-catenin might be important prognostic factors in triple negative breast carcinoma. DKK1 might be a valuable biomarker in predicting the prognosis of patients with earlier stage or no lymph node metastasis. It is possible that through further understanding of the role of Wnt/beta-catenin pathway activation, beta-catenin would be a potential therapeutic target for the triple negative breast cancer.
Highlights
Breast cancer is a disease with heterogeneous nature and our understanding of the breast subtypes had been previously based on histopathology and immunohistochemical criteria
We investigated the expression of DKK1 and beta-catenin in tumor specimens from 85 patients with breast cancer and the correlation between DKK1 and beta-catenin together with other clinical pathological features of prognosis in this study
Expression of DKK1 in Breast Cell Lines The levels of DKK1 mRNA in 6 different breast carcinoma cell lines were compared with those in the normal MCF10A breast cell line and in Hela cell line
Summary
Breast cancer is a disease with heterogeneous nature and our understanding of the breast subtypes had been previously based on histopathology and immunohistochemical criteria. Women with triple-negative breast cancers are reported to have an increased likelihood of distant recurrence and death than women with other types of breast cancer within 5 years after diagnosis but not there-after [3]. They have been reported to have a tendency toward visceral (versus bone) metastasis, local relapse and cerebral metastases [4,5]. The prognosis of breast cancer patients may be influenced by traditional parameters, such as pathology type, lymph node status, tumor size, stage and expression of hormone receptors. We investigated the prognostic importance of dickkopf-1(DKK1) and beta-catenin expression in triple negative breast cancers
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