The high expression levels of tumor protein p53 (TP53) observed in laboratory studies of pterygium seem to contradict the fast-growing nature of its clinical behavior, and TP53 mutations have been suggested.
Our study demonstrated that inactivation of p53 in pterygium may influence miR-200a, resulting in ZEB1/ZEB2 up-regulation and EMT processing of pterygium.
These studies indicate that tumor suppressor gene p53 and other genes associated with DNA repair, cell proliferation, migration and angiogenesis are critical for the development of pterygium.
We studied, with immunohistochemistry, the presence and localization of thymine dimers in the epithelial and stromal components of the human primary pterygium and its recurrences with a special emphasis on the vascular network and its interactions with the p53 tumor suppressor gene protein.
Molecular genetic alterations reported in association with pterygium include loss of heterozygosity (LOH), point mutations of proto-oncogenes, such as K-ras and alterations in the expression of tumor suppressor genes, such as p53 or p63.
HPV 16/18 E6 contributes to HPV-mediated pterygium pathogenesis as it is partly involved in p53 inactivation and is expressed in HPV DNA-positive pterygium.
Several researchers believe that pterygium is UV-related and that abnormal expression of p53 protein and infection with human papillomavirus (HPV) are risk factors for pterygium, but their experiments have been inconclusive.
Therefore, BPDE-like DNA adduct, p53 protein expression and p53 gene mutation were examined in this study to provide more molecular evidence to understand the cause of p53 gene mutation in pterygium.
After p53 protein was found to be abnormally expressed in the epithelium, researchers suggested that a pterygium may be a tumor, but additional evidence is required to support this hypothesis.
We have analyzed the status and expression of the p53 gene in epithelial cells derived from pterygium and have demonstrated that the p53 gene has undergone a monoallelic deletion.
Since mutated p53 is one of the most frequent gene abnormalities in human cancer, we hypothesized that mutation of p53 may play an important role in growth and recurrence of pterygia, a dysplasia of the conjunctiva.
Fluorescence telomeric repeat amplification protocol was used to measure telomerase activity in whole pterygium samples from 9 cases and in the epithelium and stroma of pterygium from another 10 cases. p53 protein content was measured by enzyme-linked immunosorbent assay (ELISA) in tissues obtained from 7 eyes, as well as in epithelial cell suspensions collected by brush cytology in 8 eyes.
Loss of heterozygosity (LOH), increased P53 expression and the presence of oncogenic viruses, such as human papilloma virus (HPV) and herpes simplex virus (HSV), have been detected in pterygia, supporting the possible neoplastic nature of the lesion.
We examined specimens--1 of pinguecula, 13 of pterygia (7 primary, 1 recurrent, 1 with dysplasia, and 4 primary not tested for p53), and 10 of limbal tumors (2 with actinic keratosis dysplasia, 1 with conjunctival intraepithelial neoplasia, 3 with carcinoma in situ, and 4 with squamous cell carcinoma)-expressing p53.
Abnormal p53 expression in the epithelium of primary and recurrent pterygium specimens suggests that pterygium is a growth disorder rather than a degeneration.