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Accumulation of p53 Protein in Human Esophageal Precancerous Lesions: A Possible Early Biomarker for Carcinogenesis¹

Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855 [L-D. W., J-Y. H., H. G., C. S. Y.], and Henan Institute of Medical Sciences, Henan Medical University, Zhengzhou, China [L-D. W., S-L. Q.]

The level of p53 protein was determined immunohistochemically in normal tissues and tissues with different severities of lesions (basal cell hyperplasia, dysplasia, carcinoma in situ, and carcinoma) from surgically resected human esophagi and esophageal biopsies of symptom-free subjects. The samples were from an area with high esophageal cancer incidence in northern China (Linxian and Huixian in the Henan province). Tissue sections were incubated with p53 antibodies for immunostaining. Conventional hematoxylin and eosin stain was also used. In surgically resected esophageal specimens, elevated p53 protein levels were found in the cell nuclei in tissues with precancerous and cancerous lesions. From basal cell hyperplasia to dysplasia to carcinoma in situ, the p53 immunostain-positive cells increased in number, and their distribution had roughly the same pattern as that of the proliferating cells. However, positive stain was not observed in the dividing basal cells of the normal epithelium of the surgically resected tissues. A similar pattern of immunostaining was observed in the abnormal tissues of the biopsy samples from the symptom-free subjects. An intriguing observation is that some p53 immunostain-positive cells were observed in 3 of 6 cases of histologically normal epithelia of biopsy samples. Only the papillary immunostaining pattern was observed in these three "normal" cases. Although the molecular basis for such positive stain remains to be investigated, it is possible that p53 protein accumulation occurs early in the pathogenesis of esophageal cancer and that p53 mutation is closely associated with the initiation of this cancer. The accumulation of p53 protein may be a promising early biomarker for identifying high-risk subjects for esophageal cancer.

¹ Supported in part by NIH Grant CA37037 and Center Grant ES05022.

² To whom requests for reprints should be addressed.

Received 10/ 7/92. Accepted 2/ 4/93.

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