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 protein alterations in human esophageal carcinogenesis, we investigated immunohistochemically the distribution patterns of Waf1p21, pRb, p16 and p53 in 22 cases of surgically resected esophageal cancer as well as in the neighboring non-cancerous squamous epithelia. Waf1p21 protein was detected in 13 of the 20 cases of well-differentiated squamous-cell carcinoma (SCC), where the Waf1p21-positive cells were located mainly in the interior layers of the cancer nests. Conversely, p53-positive cells were found mostly in the peripheral layers. Cells containing both Waf1p21- and p53-positive immunostaining were not observed in a double-immunostaining experiment. p16 was detected in both the nucleus and cytoplasm in 3 of the 22 cases of SCC. All of these p16-positive cancers showed an absence of pRb immunostaining; this result is consistent with the idea that expression of p16 is regulated negatively by pRb. Eleven of the 22 esophageal SCCs (50%) showed extensive pRb immunostaining cells, and the remaining 11 cases displayed a few pRb-positive cells or an absence of pRb immunostaining. In a majority of the morphologically normal squamous-cell epithelia samples, immunostaining of Waf1p21 and pRb was found in most of the cells in the parabasal layers (proliferation compartment), where PCNA-positive cells also resided. In the pre-cancerous lesions, Waf1p21 and pRb were detected in cells surrounding 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".