Predictive and Prognostic Significance of p27, Akt, PTEN and PI3K Expression in HER2-Positive Metastatic Breast Cancer
| Autor: | Gokhan Demir, Coskun Tecimer, Levent Dalar, Mustafa Bozkurt, Nuray Başsülü, Gulen Dogusoy, Kerem Okutur, Nil Molinas Mandel, Kezban Nur Pilanci, Kübra Aydın |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty Receptor ErbB-2 Epidemiology Antineoplastic Agents Breast Neoplasms Disease-Free Survival Phosphatidylinositol 3-Kinases Breast cancer Trastuzumab Proliferating Cell Nuclear Antigen Internal medicine medicine Humans PTEN skin and connective tissue diseases Protein kinase B PI3K/AKT/mTOR pathway Aged Retrospective Studies Aged 80 and over biology Akt/PKB signaling pathway business.industry PTEN Phosphohydrolase Public Health Environmental and Occupational Health Middle Aged medicine.disease Metastatic breast cancer Treatment Outcome Cancer research biology.protein Immunohistochemistry Female business Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Asian Pacific Journal of Cancer Prevention. 16:2645-2651 |
| ISSN: | 1513-7368 |
| DOI: | 10.7314/apjcp.2015.16.7.2645 |
| Popis: | Background: The phosphatidylinositol 3’-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. Materials and Methods: Fifty-four HER2positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient’s breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. Results: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). Conclusions: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC. |
| Databáze: | OpenAIRE |
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