Significance of DNA Replication Licensing Proteins (MCM2, MCM5 and CDC6), p16 and p63 as Markers of Premalignant Lesions of the Uterine Cervix: Its Usefulness to Predict Malignant Potential
Overexpression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) and increasing mast cell density (MCD) in premalignant and malignant oral lesions have been documented.
Hypermethylation-induced transcriptional silencing of MGMT and p16 genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy.
Hypermethylation-induced transcriptional silencing of MGMT and p16 genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy.
It is now well established that COX-2 is overexpressed in many premalignant, malignant, and metastatic cancers, including hepatocellular carcinoma (HCC).
Elevated cyclooxygenase-2 (COX-2) expression is observed in a variety of premalignant neoplastic tissues, suggesting COX-2 expression might serve as a potential indicator of subsequent tumor development.
We have previously identified a rare subpopulation of variant human mammary epithelial cells (vHMEC) with repressed p16INK4A that exist in disease-free women yet display premalignant properties, suggesting that they have engaged the process of malignant transformation.
Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions.
Topical application of a bioadhesive black raspberry gel modulates gene expression and reduces cyclooxygenase 2 protein in human premalignant oral lesions.
Although COX-2 is commonly overexpressed in a variety of premalignant and malignant conditions including oral leukoplakia and squamous cell carcinoma, relatively little research has compared the effects of various COX-2 inhibitors (celecoxib, NS-398, nimesulide and meloxicam).
We evaluated chromosomal instability in premalignant Barrett's esophagus tissue using high resolution Affymetrix mapping 100K SNP arrays as patients progressed through three molecular stages of disease-CDKN2A(LOH) only, CDKN2A(LOH)/TP53(LOH), and CDKN2A(LOH)/TP53(LOH) with aneuploidy.
We found that celecoxib inhibited the growth of premalignant and malignant human bronchial epithelial cells with IC(50) values between 8.9 and 32.7 micromol/L, irrespective of cyclooxygenase-2 (COX-2) expression.
While COX-2 expression in normal breast epithelium in vivo has not been proven to be linked to an increased risk of breast cancer, its over-expression in the premalignant model in vitro does provide preliminary evidence that COX-2 inhibition may be a useful chemoprevention strategy.
Only two premalignant lesions showed absence of p16 expression, of which one (carcinoma in situ) was hypermethylated at the p16(INK4a) promoter region and the other (severe dysplasia) showed BMI-1 expression.
Expression of p16(INK4a) may aid in the diagnosis of HPV-related lesions and as such may be of value as a surrogate marker in the diagnosis of vulvar premalignant and malignant lesions.
Cyclooxygenase-2 (Cox-2), an enzyme that catalyzes the synthesis of prostaglandins, is overexpressed in a variety of premalignant and malignant conditions, including urinary bladder cancer.
The high frequency of mutation, deletion, and promoter silencing of the gene encoding p16(INK4A) (p16) in premalignant dysplasias and squamous cell carcinomas (SCC) of epidermis and oral epithelium classifies p16 as a tumor suppressor.
Promoter methylation of the death-associated protein kinase and p16 gene has been found in about 55% and 30% cases of head and neck squamous cell carcinoma respectively but has not yet been analyzed in cutaneous premalignant and malignant lesions.
The COX-2 enzyme has been reported to be over-expressed in premalignant and malignant states, including in Barrett's esophagus and esophageal adenocarcinoma.
The results revealed that nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma; the frequency of nuclear overexpression of beta-catenin and p16 in lymph node metastases was significantly higher than that in distant metastases (p < 0.05).