Cases of UDEC had mutations in genes associated with endometrial adenocarcinomas (eg, TP53, PTEN, PIK3CA) and occasionally SMARCA4, while SDUS was characterized solely by inactivating mutations in SMARCA4.
The presence of aneuploidy, p53 positivity and development of HGD or adenocarcinoma on follow-up indicate that CCA likely represents a dysplastic lesion (at least LGD) and is a histological marker of neoplastic progression.
Despite the propensity for gastric and esophageal adenocarcinomas to select for recurrent missense mutations in TP53, the precise functional consequence of these mutations remains unclear.
High-level p53 immunostaining in patients with AC was associated with advanced tumor (P=0.019) and Union for International Cancer Control stages (P=0.004), grading (P=0.027) and the resection margin status (P=0.006).
We investigated the expression patterns of Ki67 and p53 in metastatic pancreatic adenocarcinomas and analyzed their relationship with disease progression-free survival (PFS) and overall survival (OS) in the overall study population and in patients treated with a gemcitabine-containing chemotherapy versus FOLFIRINOX chemotherapy.
Depletion of growth factors or concurrent Trp53 deletion resulted in its robust enrichment, invariably leading to development of PanIN or large high-grade adenocarcinoma, respectively, consistent with in vivo mouse studies for the same genotype.
p65BTK was significantly over-expressed in EGFR-wild type (wt) adenocarcinomas (AdC) from non-smoker patients and its expression was also preserved at the metastatic site. p65BTK was also over-expressed in cell lines mutated for KRAS or for a component of the RAS/MAPK pathway and in tumors from Kras/Trp53 null mice.
The interface between "adenocarcinoma" and "hyperplastic polyp" components was fairly sharp, and the adenocarcinoma components had copy number alterations and TP53 mutations, whereas the hyperplastic polyp components had only single nucleotide polymorphisms, which were also found in adenocarcinoma components.
Finally, we screened colorectal cancer patients and identified recurrent somatic PPM1D mutations in a fraction of colon adenocarcinomas that are p53 proficient and show defects in mismatch DNA repair.
While PTEN inactivation leads to PC, it is not sufficient for metastasis, the loss of PTEN concurrently with the inactivation of both TP53 and RB1 empower lineage plasticity in PC cells, which substantially promotes PC metastasis and the conversion to PC adenocarcinoma to neuroendocrine PC (NEPC), demonstrating the essential function of TP53 and RB1 in the suppression of PCSCs.
In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration.
There was a dramatic decrease in mutant p53 protein accumulation in the pancreatic acini, pancreas intraepithelial neoplasia lesions, and adenocarcinoma.
Furthermore, the score was able to predict recurrence-free survival in patients with stage I adenocarcinoma and was also associated with smoking status.<b>Conclusions:</b> The P53 deficiency score was a better predictor of recurrence-free survival compared with P53 mutation status and provided additional prognostic values to established clinical factors.<b>Impact:</b> The P53 deficiency score can be used to stratify early-stage patients into subgroups based on their risk of recurrence for aiding physicians to decide personalized therapeutic treatment.
Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas.
Multiple mutations were significantly associated with younger age (p = 0.0006), female sex (p = 0.012), smoking status (p = 0.002) and adenocarcinoma histology (p = 0.0001).TP53, KRAS and EGFR were the most common mutations.
MLL2 and KRAS mutations were only seen in adenocarcinoma ex goblet cell carcinoids and TP53 mutations were limited to poorly differentiated adenocarcinoma ex goblet cell carcinoids (2/34).
Esophageal adenocarcinomas have mutations in tumor protein p53 and mutations that activate receptor-associated tyrosine kinase, vascular endothelial growth factor, and cell cycle pathways, whereas esophageal squamous tumors have a distinct set of mutations.
We found EGFR expression is higher in the squamous cell carcinomas than in adenocarcinomas (p=0.043), and that nuclear p53 staining correlated with lower differentiated squamous tumors (p=0.034).
Immunohistochemically, the adenocarcinomas were positive for MUC6 (4/5), PAX8 (3/5), CK7 (5/5), CK20 (1/5), CDX2 (5/5), CA19.9 (5/5), CEA (4/5), CA125 (5/5), and hepatocyte nuclear factor 1β (5/5). p16, estrogen receptor, and Napsin A were negative in all cases tested, whereas p53 exhibited mutation-type staining in 3/5 cases.