期刊
ONCOTARGET
卷 6, 期 2, 页码 1327-1339出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2675
关键词
endometrial carcinoma; endometrial hyperplasia; metastasis; body mass index; PI3Kinase
资金
- Helse Vest
- University of Bergen
- Norwegian Cancer Society
- Research Council of Norway
- Bergen Medisinske Forskningsstiftelse
- MD Anderson Cancer Center Support Grant (CCSG) from the National Cancer Institute [CA016672]
- [P50 CA098258]
Obesity is linked to increased incidence of endometrioid endometrial cancer (EEC) and complex atypical hyperplasia (CAH). We here explore pattern and sequence of molecular alterations characterizing endometrial carcinogenesis in general and related to body mass index (BMI), to improve diagnostic stratification and treatment strategies. We performed molecular characterization of 729 prospectively collected EEC and CAH. Candidate biomarkers were identified in frozen samples by whole-exome and Sanger sequencing, oligonucleotide gene expression and Reverse Phase Protein Arrays (investigation cohort) and further explored in formalin fixed tissues by immunohistochemistry and Fluorescent in Situ Hybridization (validation cohort). We here demonstrate that PIK3CA mutations, PTEN loss, PI3K and KRAS activation are early events in endometrial carcinogenesis. Molecular changes related to KRAS activation and inflammation are more common in obese CAH patients, suggesting different prevention and systemic treatment strategies in obese and non-obese patients. We also found that oncoprotein Stathmin might improve preoperative diagnostic distinction between premalignant and malignant endometrial lesions.
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