Patterns of p53 and Ki-67 protein expression in epithelial dysplasia from the floor of the mouth

Abstract

Oral squamous cell carcinoma develops through a series of precancerous stages manifested at the microscopic level as epithelial dysplasia. Mutation of the p53 tumour suppressor gene is thought to be an important component of oral carcinogenesis. p53 regulates cell proliferation and DNA repair by inhibiting the cell cycle at G1/S; loss of p53 function may therefore lead to aberrant cell kinetics. To date, no studies have examined the relationship between p53 protein and alterations in cell kinetics in oral epithelial dysplasia from a single anatomical site. Serial sections were studied from 40 routinely processed biopsy specimens of epithelial dysplasia from the floor of the mouth. The expression of p53 protein was determined by immunohistochemistry and cell proliferation was studied by immunostaining for the cell cycle‐dependent protein Ki‐67. The number of positive cells per millimetre of basement membrane was determined using computer image analysis and compared with site‐matched normal controls. The mean p53 labelling index (LI) in normal mucosa was low, 3·48±0·92 [mean±95 per cent confidence interval (CI)], and increased sharply in the transition from mild (42·49±21·71) to moderate (104·86±51·39) epithelial dysplasia. The mean p53 LI for severe dysplasia was 119·09±56·50. Differences were also observed in the distribution of p53‐positive cells between grades of dysplasia, with the development of compact p53‐positive foci in severe dysplasia. Mean proliferative indices, as determined by Ki‐67 expression, were significantly associated with grade of epithelial dysplasia. Furthermore, there was a significant correlation between p53 LI and Ki‐67 score (r2=0·37, P=0·01). It is concluded that altered p53 protein expression is probably an early event in oral carcinogenesis in the floor of the mouth and is associated with dysregulation of cell proliferation at this site. © 1997 John Wiley & Sons, Ltd.

Histopathological evaluation including cytokeratin 13 and Ki-67 in the border between Lugol-stained and -unstained areas

“…The differences in expression clearly demonstrated the boundary line, which was consistent with the pathological border in HE-stained sections. Ki-67 protein is a representative molecular marker of proliferating cells that is extensively used in examination of oral epithelial dysplasia and squamous cell carcinoma (9,10). In the present study, Ki-67 protein expression was detected in the basal/parabasal layers of Lugol-stained areas, whereas Ki-67 positive cells were increased in Lugol-unstained areas and also found in suprabasal prickle cell layers.…”

“…The expression of specific types, such as cytokeratin (CK)4 and CK13, is decreased in dysplastic lesions in the oral epithelium, and such changes have been associated with the development of oral dysplasia and squamous cell carcinomas (7,8). On the other hand, Ki-67 is a representative molecular marker of proliferating cells, and its labeling index correlates with the grade of dysplasia and severity of malignancy (9,10). In the present study, to elucidate the changes related to cell differentiation and proliferation in borders distinguished by Lugol-staining in and epithelial dysplasia surrounding squamous cell carcinoma, we investigated the histological appearance in the borders between Lugol-stained and -unstained areas using hematoxylin and eosin (HE) and periodic acid-Sciff (PAS)-staining.…”

Direct Correlation between Proliferative Activity and Dysplasia in Pancreatic Intraepithelial Neoplasia (PanIN): Additional Evidence for a Recently Proposed Model of Progression

“…Although the original Ki-67 antibody was reactive only in frozen sections, a newer antibody to an epitope of Ki-67 (Mib-1) is active in formalin-fixed, paraffin-embedded tissues. It has therefore been used extensively to evaluate malignancies in many different organ sites (15)(16)(17)(18)(19)(20)(21)(22).…”

Skp2 is oncogenic and overexpressed in human cancers

“…To determine the number of Skp2-, p27-, or Ki-67-positive cells as a proportion of the total epithelial cell population in normal epithelial or lesional tissue, an image analysis system was used as previously described (IBAS System, Kontron Electronik, Dusseldorf, Germany) (13,19,26). At 200ϫ magnification, the total number of epithelial cell nuclei in each field was counted.…”

“…We previously reported reduced p27 protein expression in oral precancerous lesions and carcinomas compared with normal epithelial controls (13). Oral carcinomas have a significantly higher proliferative index than normal epithelium (14)(15)(16)(17)(18)(19)(20), and increased cell proliferation is also observed in precancerous oral epithelial dysplasia compared with nondysplastic epithelium (14)(15)(16)(20)(21)(22). Therefore, a progressive dysregulation of cell proliferation appears early in oral carcinogenesis.…”