When compared to a reference of tumor tissue p16 IHC in 783 OPSCC patients, the clinic-HPV<sub>sero</sub> model incorporating a composite of 20 HPV serological antibodies (HPV<sub>sero</sub> ) and 4 clinical factors (c-index: 0.96) performed better than using HPV<sub>sero</sub> (c-index: 0.92) or HPV<sub>mi</sub> (c-index: 0.76) alone.
Mechanistically, these effects were mediated by attenuation of cell cycle progression, as Western blot analyses demonstrated upregulation of the tumor suppressor p21/CDKN2A and downregulation of the cell cycle regulator Cyclin D1 as well as reduced levels of phosphorylated ribosomal protein s6 (pRPS6) and retinoblastoma protein (pRb).
DNA mismatch repair protein expression studies disclosed loss of nuclear immunostaining of MSH6 protein, pointing to the possibility of an underlying rare MSH6 variant of the Muir-Torre syndrome, not yet described in the ophthalmic literature. p16 nuclear positivity was also found in the tumor cells, indicating the possible role of high-risk human papillomavirus as an additional factor in the genesis of the tumor.
HPV 16 and/or 18 were detected in 156 (80%) tumors. p16 was positive in 186 (96%) carcinomas, but eight tumors (4%) were negative forp16 (seven squamous cell carcinomas, one adenocarcinoma); 5/8 caused by HPV 16 and/or 18.
Seven tissue microarrays were constructed. p16 protein expression was studied in 114 cases, of which 35/114 (30.7%) cases showed strong expression and the majority of them had ER-positive tumor (57.6%), and it was statistically significant (P < 0.0074).
Furthermore, methylated RASSF1A and p14/ARF were associated with the grade of CRC but not associated with the age of patients, family history, or tumor location.
Additional FISH analyses detected a 9p21/CDKN2A double deletion, frequently reported in melanomas but not in nevi, in the tumor initially diagnosed as a Spitz nevus with a favor malignant p16-Ki-67-HMB45 score.
The total mutational burden was similar between human papillomavirus (HPV)-negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors.
OncoScan analysis showed genetic changes that define field cancerization of the p16 negative tumor as revealed by mosaicism in both loss of heterozygosity and copy number alterations in cancer-associated genes located on 3p, 7p, 9p 11q, and 17p.
<i>K</i><sub>ep</sub> kurtosis was significantly higher in p16 tumors, and <i>V</i><sub>e</sub> min was significantly lower in p16 tumors compared to the p16 negative tumors.
Our study pointed out the utmost relevance of CDKN2A homozygous deletion as an adverse prognostic factor in the 2 broad categories of IDH-mutant gliomas stratified on 1p/19q codeletion and suggests that the grading of these tumors should be refined.
This study showed mutations in the tumor suppressor CDKN2A gene and the NRAS oncogene in 62.5% and 75%, respectively of the samples that had mutations in the ABCB5 gene.
A total of 28 studies with 2612 nasopharynx cancer patients were included in the meta-analysis. p16 protein expression was significantly associated with the risk, lymph node metastasis, TNM-stage (tumor-node-metastasis), distant metastasis, and T stage of nasopharynx cancer (Risk, OR = 17.82, 95% CI = 11.20-28.35; Lymph node metastasis, OR = 2.11, 95% CI = 1.42-3.14; TNM-stage, OR = 2.25, 95% CI = 1.54-3.28; Distant metastasis, OR = 3.43, 95% CI = 1.55-7.58; T-stage, OR = 1.72, 95% CI = 1.27-2.33).
The tumor suppressor gene FHIT is lowly expressed in breast cancer tissues and positively associated with the expression of the multi-tumor suppressor gene p16.
Distinct Roles of Direct Transduction Versus Exposure to the Tumor Secretome on Murine Endothelial Cells After Melanoma Gene Therapy with Interferon-β and p19Arf.
Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression.
Cancers rewire metabolism to facilitate proliferation; however, it is not well appreciated how this enables senescence bypass.Recent work by Buj et al. demonstrates that loss of the tumor suppressor p16 engages a mTORC1-dependent increase in nucleotide pools to override senescence.
The p16Ink4a plays an important role in tumor suppression, whereby its deletion, mutation, or epigenetic silencing is a frequently observed genetic alteration in prostate cancer.
The median tumor mutation burden for GBC patients was 5.4 (range: 0.8-36.74) mutations/Mb, and the most common mutations were in TP53 (73%), CDKN2A (25%) and PIK3CA (20%).