Longstanding molecular observations implicate PTEN inactivation as a major driver of endometrioid carcinomas; TP53 inactivation as a major driver of most serous carcinomas, some high-grade endometrioid carcinomas, and many uterine carcinosarcomas; and inactivation of either gene as drivers of some clear cell carcinomas.
Use of Sox9-Cre-LoxP-based approach to coordinately delete PTEN and activate Kras in the adult mouse resulted in not only development of low-grade biliary lesions (ICC and extrahepatic bile duct carcinoma, ECC) but also pancreatic carcinomas.
We examined the diagnostic and prognostic value of altered reticulin framework and the immunoprofile of biomarkers including IGF-2, proteins involved in cell proliferation and mitotic spindle regulation (Ki67, p53, BUB1B, HURP, NEK2), DNA damage repair (PBK, γ-H2AX), telomere regulation (DAX, ATRX), wnt-signaling pathway (beta-catenin) and PI3K signaling pathway (PTEN, phospho-mTOR) in a tissue microarray of 50 adenomas and 43 carcinomas that were characterized for angioinvasion as defined by strict criteria, Weiss score, and mitotic rate-based tumor grade.
PTEN was preserved in 166 (59%) tumors, partially lost in 38 (14%), and absent in 75 (27%), with lower expression in malignant mesotheliomas compared to carcinomas, though not significantly (p = 0.084).
We assessed the relationship between ERG and PTEN protein expression in cribriform architecture prostatic carcinomas and adjacent acinar non-cribriform carcinoma and determined the interobserver variability in assessment of these markers.
It was reported that the E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated gene (NEDD4) (also known as NEDD4-1) negatively regulated phosphatase and tensin homolog deleted on chromosome 10 protein levels through poly-ubiquitination and proteolysis in carcinomas of the prostate, lung, and bladder.
The E3 ubiquitin ligase NEDD4 (also known as NEDD4-1) has been reported to negatively regulate PTEN protein levels through poly-ubiquitination and proteolysis in carcinomas of the prostate, lung, and bladder, but its effect on PTEN in the breast has not been studied extensively.
Genetic studies have demonstrated that endometriotic lesions have mutations in genes directly related to neoplasms, in particular the p53, KRAS, PTEN, and ARID1A genes, which suggests a direct transition from a subset of endometriotic lesions to invasive carcinomas.