A series of 8 tubo-ovarian carcinosarcomas was characterized for the following: (i) immunohistochemical expression of MNF116, epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4), and p53; (ii) mutational profiling of KRAS, BRAF, PIK3CA, NRAS, TP53, and DICER1 genes.
Nevertheless, immunohistochemistry is the gold standard for the diagnosis of carcinosarcomas, since it has been demonstrated that CEA, EMA, pancreatin, chromogranin A, CD56 and synaptophysin staining are highly specific markers for the carcinomatous components, while desmin, vimentin and smooth muscle/sarcomeric actin show affinity for the sarcomatous elements.
Multiple mammary tumors of adenocarcinoma type were induced in all females, while 83% of treated males developed adenocarcinomas, sarcomas and transitional carcinosarcomas, as evidenced by casein and vimentin immunoreactivity.
We aimed to systematically evaluate the characteristics of HER2 expression/amplification in gynecologic carcinosarcomas using standardized staining methods and scoring criteria.
Carcinosarcomas with rhabdomyosarcomatous differentiation showed frequent mutations in TP53 (7/8, 88%) and the PI3K/PTEN pathway (6/8, 75%) but lacked DICER1 mutations.
A series of 8 tubo-ovarian carcinosarcomas was characterized for the following: (i) immunohistochemical expression of MNF116, epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4), and p53; (ii) mutational profiling of KRAS, BRAF, PIK3CA, NRAS, TP53, and DICER1 genes.
Whole-exome sequencing studies have recently demonstrated mutations or aberrant activation of multiple genes/pathways in CSs including HER2, PI3K/AKT/mTOR, EGFR, MAPK, genes related to histones and chromatin structure, and genes related to cell-cycle regulation.
Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2) open up new possibilities in the field of target therapy.
<i>In vivo</i> studies confirmed that SYD985 is more active than T-DM1 in CS and highly effective against HER2/neu expressing xenografts and PDX.<b>Conclusions:</b> SYD985 may represent a novel and highly effective ADC against HER2-expressing CS.
Of 24 patients with actionable mutations, five were given genotype-matched drugs corresponding to actionable mutations: everolimus to PIK3CA mutation in parotid carcinosarcoma (partial response) and tracheal squamous cell carcinoma (stable disease; 21% reduction), sorafenib to PDGFRA mutation in auditory canal adenocarcinoma (partial response), sorafenib to BRAF mutation in microcytic adnexal carcinoma (progressive disease), and afatinib to ERBB2 mutation in esophageal adenocarcinoma (progressive disease).
Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship.
HER2/neu amplified cell lines SARARK6 and SARARK9 were significantly more sensitive to neratinib than the five non-HER2/neu amplified carcinosarcoma cell lines (mean±SEM IC50:0.014μM±0.004vs.0.164μM±0.019 p=0.0003).
Clinical evidence led us to partially inactivate Pten and Tp53 in the smooth muscle lineage of mice, which developed high-grade undifferentiated pleomorphic sarcomas, leiomyosarcomas, and carcinosarcomas that widely recapitulate the human disease, including the aberrant karyotype and metastatic behavior.
EGFR, HER2, KRAS, p53, CTNNB1, BRAF and PIK3CA mutations were assessed by direct sequencing, ALK, EGFR and HER2 gene status by fluorescence in situ hybridization (FISH), and ALK protein expression by immunohistochemistry (IHC) in 20 pleomorphic carcinomas (PLC), two pulmonary blastomas (PB) and one carcinosarcoma (CS).
Immunohistochemical and gene mutation analyses revealed that both the carcinomatous and sarcomatous tumour cells of the carcinosarcoma, as well as the IPMC cells, expressed TP53 and had identical mutations in KRAS and TP53 genes, indicating that these two neoplastic components of the carcinosarcoma shared a common tumorigenesis and arose from the IPMC.
We studied the pattern and frequency of defective DNA mismatch repair and TP53 alterations in the epithelial and mesenchymal components of 28 uterine carcinosarcomas.
We studied the pattern and frequency of defective DNA mismatch repair and TP53 alterations in the epithelial and mesenchymal components of 28 uterine carcinosarcomas.