Abstract
Abstract Background: Aberrant phosphatidylinositol 3-kinase (PI3K) pathway signaling occurs in a high proportion of human breast cancers and is involved in carcinogenesis, tumor progression and resistance to targeted therapies. Reduced levels of the tumor suppressor PTEN has been associated with PI3K pathway activation and is observed in ∼40% of breast carcinomas. PTEN levels have traditionally been determined in breast tumors by qualitative immunohistochemistry (IHC) and its prognostic and/or predictive value has not been clearly established. We used a novel method of quantitative in situ measurements of PTEN mRNA and protein to determine their possible prognostic and predictive value in breast cancer. Materials and methods: PTEN mRNA and protein were measured on formalin fixed paraffin embedded (FFPE) cell lines and tumor samples on tissue microarrays (TMAs) representing a retrospective cohort of 404 breast cancer cases collected from the Yale Pathology archives between 1975 and 2005. The RNAscope paired-primer method was used for PTEN mRNA in situ hybridization (ISH), with Ubiquitin C and DapB ISH probes used as positive and negative controls for each run. PTEN protein measurements were performed with monoclonal antibody 138G6 (Cell Signaling Technology). Both mRNA and protein were measured using the AQUA method of quantitative immunofluorescence. Results: Both PTEN mRNA ISH signal and protein were highly reproducible in FFPE tissues and cell lines. PTEN mRNA levels were lower in cell lines with known PTEN downregulation. In breast carcinoma samples, PTEN mRNA scores showed a positive non-linear association with protein levels. Neither PTEN mRNA nor protein showed prognostic value. However, high PTEN mRNA expression using a visually defined cutoff was associated with better outcome in a subset of Tamoxifen treated breast cancer patients. Conclusion: Initial data suggests that PTEN mRNA expression may be predictive of favorable response to endocrine therapy in breast carcinomas. However, validation in larger independent cohorts is required. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-25.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
