IMMUNOHISTOCHEMICAL STUDIES ON WAF1P21, P16, PRB AND P53 IN HUMAN ESOPHAGEAL CARCINOMAS AND NEIGHBORING EPITHELIA FROM A HIGH-RISK AREA IN NORTHERN CHINA

To better understand the roles of p53 and cell cycle-regulating protei n alterations in human esophageal carcinogenesis, we investigated immu nohistochemically the distribution patterns of Waflp21, pRb, p16 and p 53 in 22 cases of surgically resected esophageal cancer as well as in the neighboring non-cancerous squamous epithelia. Waflp21 protein was detected in 13 of the 20 cases of well-differentiated squamous-cell ca rcinoma (SCC), where the Waflp21-positive cells were located mainly in the interior layers of the cancer nests. Conversely, p53 positive cel ls were found mostly in the peripheral layers. Cells containing both W aflp21- and p53-positive immunostaining were not observed in a double- immunostaining experiment. p16 was detected in both the nucleus and cy toplasm in 3 of the 22 cases of SCC. All of these p16-positive cancers showed an absence of pRb immunostaining; this result is consistent wi th the idea that expression of p16 is regulated negatively by pRb. Ele ven of the 22 esophageal SCCs (50%) showed extensive pRb immunostainin g cells, and the remaining 11 cases displayed a few pRb-positive cells or an absence of pRb immunostaining. In a majority of the morphologic ally normal squamous-cell epithelia samples, immunostaining of Waflp21 and pRb was found in most of the cells in the parabasal layers (proli feration compartment), where PCNA-positive cells also resided. In the pre-cancerous lesions, Waflp21 and pRb were detected in cells surround ing the top of the lesioned region, p16-positive cells were scattered in the basal cell hyperplastic and dysplastic lesions and p53-positive cells existed in 2 distinct patterns: ''scattered'' and ''focal''. (C ) 1997 Wiley-Liss, Inc.