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PIK3CA mutations in ductal carcinoma in situ and adjacent invasive breast cancer.
Endocrine-related Cancer 2019 March 2
PIK3CA is one of the most frequently mutated genes in invasive breast cancer (IBC). These mutations are generally associated with hyper-activation of the phosphatidylinositol 3-kinase signaling pathway, which is negatively regulated by the tumor suppressor PTEN. Data is limited regarding the variant allele frequency (VAF) of PIK3CA and PTEN expression during various stages of breast carcinogenesis. Therefore, the aim of this study was to gain insight into PIK3CA VAF and associated PTEN expression during the progression from ductal carcinoma in situ (DCIS) to IBC. We isolated DNA from DCIS tissue and synchronous IBC. These samples were pre- screened for PIK3CA hotspot mutations using the SNaPshot assay and, if positive, validated and quantified by digital PCR. PTEN expression was evaluated by immunohistochemistry using the Histo-score (H-score). Differences in PIK3CA VAF and PTEN H-scores between DCIS and IBC were analyzed. We detected a significantly higher VAF of PIK3CA in the DCIS component compared to the adjacent IBC component (p=0.007). The expression of PTEN was significantly higher in DCIS compared to the IBC component in cases with a wild type (WT) PIK3CA status (p=0.007), while it remained similar in both components when PIK3CA was mutated. In conclusion, our data suggest that PIK3CA mutations could be essential specifically in early stages of breast carcinogenesis. In addition, these mutations do not-co-occur with PTEN expression during DCIS progression to IBC in the majority of patients. These results may contribute to further unraveling the process of breast carcinogenesis and this could aid development of patient-specific treatment.
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