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.
There was a significant relationship between VEGF-C mRNA and LVA, LMD, and LVL, while VEGF-A mRNA was only closely correlated with LMD in recurrent pterygia.
In addition, we found a significant relationship between VEGF-C mRNA expression and LMVD in grades 1, 2, and 3 pterygia, whereas VEGF-A mRNA expression correlated closely with LMVD only in grade 1 pterygia.
Antibodies raised against VEGF and p53 were used to analyze the distribution and expression of these markers in pterygium and normal human conjunctiva were used as negative control.
Other findings in pterygium include the frequent detection of HPV DNA, ocular surface changes such as the overexpression of various proteins, including defensins and phospolipases D, as well as the up-regulation of growth factors, such as bFGF or VEGF.
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.
There were no significant differences between pterygium and control groups in age, sex, and distribution of genotype and allelic frequency of VEGF-460 polymorphism.
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.
In analysis of specimens from pterygium patients as well as normal conjunctivas, VEGF121 and VEGF165 were identified as the only VEGF splice forms expressed.
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.