Wang L D, Shi S T, Zhou Q, Goldstein S, Hong J Y, Shao P, Qiu S L, Yang C S
Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, NJ 08854.
Int J Cancer. 1994 Nov 15;59(4):514-9. doi: 10.1002/ijc.2910590414.
The objective of this study was to quantify the changes in p53 and cyclin D1 protein levels in different stages of human esophageal and gastric cardia carcinogenesis in a high-risk population in Henan, China. Immunoreactivity of p53, cyclin D1 and proliferating-cell nuclear antigen (PCNA) was observed in the cell nuclei of esophageal and gastric cardia biopsies. The number of p53-immunostaining-positive cells was low in normal epithelia, slightly increased in basal-cell hyperplasia (BCH), markedly increased in dysplasia (DYS) (10-fold), and further increased in squamous-cell carcinoma (SCC) (40-fold). This pattern of change was similar to that of cell proliferation as indicated by PCNA immunostaining. On the other hand, the number of cyclin D1-immunostaining-positive cells did not increase from BCH to DYS, although a slight increase from DYS to SCC was noted. In the gastric cardia, again, the pattern of change of p53-positive cells in different stages of lesions paralleled the pattern of cell proliferation. The number of p53-positive cells was very low, much lower than that of PCNA-positive cells, in normal, chronic superficial gastritis (CSG) and chronic atrophic gastritis (CAG); therefore, the increase of p53-positive cells from CAG to DYS was more dramatic (100-fold). From DYS to adenocarcinoma (AC), the p53-positive and the PCNA-positive cells increased 4-fold. On the other hand, the number of cyclin D1-positive cells did not increase in pre-cancerous lesions, but increased slightly in AC. This study demonstrates that p53 protein accumulation increased with the progression of pre-cancerous lesions, especially in the genesis of dysplasia, both in the esophagus and in the gastric cardia. Our approach of quantitative immunohistochemistry sheds light on the mechanisms of genesis of esophageal and gastric-cardia cancers, which frequently occur together in many high-incidence areas.
本研究的目的是量化中国河南高危人群中人类食管和贲门癌发生不同阶段p53和细胞周期蛋白D1蛋白水平的变化。在食管和贲门活检组织的细胞核中观察到p53、细胞周期蛋白D1和增殖细胞核抗原（PCNA）的免疫反应性。p53免疫染色阳性细胞数量在正常上皮中较低，在基底细胞增生（BCH）中略有增加，在发育异常（DYS）中显著增加（10倍），在鳞状细胞癌（SCC）中进一步增加（40倍）。这种变化模式与PCNA免疫染色所示的细胞增殖模式相似。另一方面，细胞周期蛋白D1免疫染色阳性细胞数量从BCH到DYS没有增加，尽管从DYS到SCC有轻微增加。在贲门，同样，病变不同阶段p53阳性细胞的变化模式与细胞增殖模式平行。在正常、慢性浅表性胃炎（CSG）和慢性萎缩性胃炎（CAG）中，p53阳性细胞数量非常低，远低于PCNA阳性细胞数量；因此，从CAG到DYS，p53阳性细胞的增加更为显著（100倍）。从DYS到腺癌（AC），p53阳性和PCNA阳性细胞增加了4倍。另一方面，细胞周期蛋白D1阳性细胞数量在癌前病变中没有增加，但在AC中略有增加。本研究表明，p53蛋白积累随着癌前病变的进展而增加，尤其是在发育异常的发生过程中，在食管和贲门均如此。我们的定量免疫组织化学方法揭示了食管和贲门癌发生的机制，这两种癌症在许多高发地区经常同时发生。
