Atg7 deficiency alters progression of Braf(V600E)-driven tumors from adenomas (Braf(V600E); atg7(-/-)) and adenocarcinomas (trp53(-/-); Braf(V600E); atg7(-/-)) to benign oncocytomas that accumulated morphologically and functionally defective mitochondria, suggesting that defects in mitochondrial metabolism may compromise continued tumor growth.
Efficacy studies were performed in subcutaneous human adenocarcinoma bearing SCID beige mice along with molecular level p53 plasmid and apoptotic marker expression by PCR and western blot for all study groups.
Nucleotide changes in TP53 were significantly more frequent in adenocarcinoma cases than in squamous cell carcinoma and CIN3 (P = 0.035) and were independent from HPV infection status.
TP53 mutations were observed exclusively in four adenocarcinoma components, consistent with their role in the progression from adenoma to adenocarcinoma.
The aims of this study were to determine the expression of p53 protein in endometrial adenocarcinomas (as a potential prognostic indicator before treatment) as well as normal endometrium in imprint smears and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients.
The expression of ATM and TP53 was determined by immunohistochemistry in 397 surgically resected pancreatic ductal adenocarcinomas (Hopkins; Johns Hopkins Medical Institutions, Baltimore, MD), a second set of 159 cases (Emory; Emory University Hospital, Atlanta, GA), and 21 cancers after neoadjuvant chemoradiotherapy.
False-negative controls consisted in microdissecting fresh-frozen tumor tissues both from a patient with a Li-Fraumeni syndrome who carried a p53 constitutional mutation, and from KRas mutated adenocarcinomas.
TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs.
Concerning the histological types of lung cancer, the p53 codon 72 variant exerts risk effect on the lung carcinogenesis in patients with adenocarcinoma (OR Arg/Pro vs. Arg/Arg = 1.10, 95 % CI = 1.00-1.22, P OR = 0.048).
In case 17, mutation took place only in adenocarcinoma cells. p53 mutation was closely related with degree of differentiation, tumor-node-metastasis stage, vessel invasion and lymph node metastasis.
Among the six hot-spot codons of TP53 gene, three codons (175, 248 and 273) were the most commonly mutated in both types of cervical cancer, one codon (249) mainly in squamous cell carcinoma and one codon (282) only in adenocarcinoma.
Cdx2, mucin (MUC) series (MUC2, MUC5AC and MUC6), p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining.
We conclude that Fbw7 and p53 synergistically suppress adenocarcinomas that mimic advanced human CRC with respect to histopathology, metastasis, and CIN.
To the best of our knowledge, this is the first study evaluating IGF2 by IHC, as well as, correlating it with the expression of the two tumor suppressor genes, p53 and FHIT, in esophageal tissue. p53 expression was threefold higher than normal in dysplasias of squamous epithelium and adenocarcinoma, while it was eightfold higher in squamous cell carcinoma.
While P53 appears to be wild-type in the NE cells of benign prostate and adenocarcinoma, immunohistochemical studies show that the majority of the NE tumor cells in SCNC are positive for nuclear p53, suggesting that the p53 is mutated.
Our results suggest that HER2-positive Barrett's adenocarcinomas are associated with p53 overexpression and lesion protrusion at the early disease stage.
Finally, limiting dilution transplantation revealed that p53 null claudin-low tumors are highly enriched for TICs compared with the more common adenocarcinomas arising in the same model, thus providing a unique preclinical mouse model to investigate the therapeutic response of TICs.
FRα expression was correlated with thymidylate synthase and p53 expression in NSCLCs, and with epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten rat sarcoma viral (KRAS) gene mutations in adenocarcinomas.