- Expression of p53, p21waf1/cip1, Cyclin D1 and Rb in Gastric Epithelial Proliferative Lesions.
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Hyoung Joong Kim, Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo
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Korean J Pathol. 2002;36(4):222-231.
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 Abstract
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- BACKGROUND
Aberrations of cell cycle-related genes have been reported to contribute to the formation and development of various human tumors. To investigate the gastric carcinogenesis, the expression of cell cycle-related genes (p53, p21wafl/cipl, cyclin D1 and Rb protein) compared to the morphological changes of gastric epithelial lesions were studied.
METHODS
The expression of p53, p21wafl/cipl, cyclin D1 and Rb protein was immunohistochemically studied in a series of surgical specimens including the 36 normal/regenerating lesions and the 127 gastric epithelial proliferative lesions (GEPLs). The gastric epithelial proliferative lesions consisted of 25 regenerating epithelia with atypias (REAs), 27 low grade gastric dysplasias (LGDs), 17 high grade dysplasias (HGDs), 24 early gastrc carcinomas (EGCs), and 34 advanced gastric carcinomas (AGCs).
RESULTS
The frequency of p53 protein overexpression was significantly associated with histologic grades of GEPLs (p=0.031); occurring in 4% of REAs, in 14.8% of LGDs, in 23.5% of HGDs, in 41.7% of EGCs and 58.9% of AGCs. The p21 wafl/cipl immunohistochemical reaction showed superficial eccentric positivity, representing an inverse correlation with histologic grades of GEPLs (p=0.04); occurring in 83.4% of normal/regenerating lesions, in 80% of REAs, in 74.1% of LGDs, in 29.4% of HGDs, 20.8% of EGCs and 8.8% of AGCs.
Although Cyclin D1 and Rb proteins were expressed highly in the GEPLs, the frequency of both proteins were insignificantly associated with histologic grades of GEPLs (p=0.092). However, cases with both the Rb and cyclin D1 positivity were increased with statistical significance along histologic grades of GEPLs (p=0.044).
CONCLUSIONS
The altered expression of p53, p21, Rb, and cyclin D1 was considered to be related to dysplastic progression and advancement of malignancy in GEPLs.
Therefore, immunohistochemical studies of cell cycle related proteins and a combined analysis may be useful for estimating and following up cases of GEPLs.
- Expression of Glutathione S-Transferase, E-Cadherin, and Catenins during N,N-Diethylnitrosamine-Induced Hepatocarcinogenesis in Rat Liver.
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Hyoung Joong Kim, Yon Sik Yoo, Tae Jin Lee, Mi Kyung Kim, Eon Sub Park, Jae Hyung Yoo
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Korean J Pathol. 2000;34(12):982-993.
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Abstract
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- N,N-Diethylnitrosamine (DEN) has been proved to have carcinogenic potential in the initiation or promotion stage and the transformed cells proliferate to form preneoplastic nodules which are positive for placental form of glutathione S-transferase (GST-P). E-Cadherin, a member of the cadherin family, is expressed in epithelial cells.
To evaluate the role of adhesion molecules (E-Cadherin, alpha-catenin, and beta-catenin), which have not been well understood in carcinogenesis, we investigated the changes of E-cadherin, alpha-Catenin and beta-Catenins by immunohistochemistry and immunoblotting in DEN-induced hepatocarcinogenesis of rat liver. In addition, the sequential analysis of histopathology and the expression of GST-P were also examined. Immunoreactive areas for GST-P were gradually increased from early period of carcinogenesis and strong GST-P positive foci were noted in various lesions, especially in the clear cell and eosinophilic cell nodules. Immunohistochemically, the E-Cadherin expression was increased in DEN-treated preneoplastic nodules in 4 and 10 weeks and hepatocellular carcinomas displayed relatively reduced expression compared with the hyperplastic nodules. But alpha- and beta-catenin expression was increased in hyperplastic nodules and hepatocellular carcinomas. Immunoblotting studies revealed that the level of alpha-catenin (cytosol and membranous fraction) was overexpressed in hyperplastic nodules as well as hepatocellular carcinomas, which showed markedly increased expression. The membranous fraction of beta-catenin was markedly increased in 10 weeks of DEN treatment and slightly reduced in hepatocellular carcinomas.
These findings suggest that during DEN-induced hepatocarcinogenesis, the clear cell and eosinophilic cell nodules expressing GST-P in their cytoplasm are early transformed cell nodules. The altered expression of E-Cadherin and catenins is closely related with tumor propagation. Loss or reduced expression of E-cadherin may play a role in the progression of late hyperplastic nodule to hepatocellular carcinoma in DEN-induced rat hepato carcinogenesis.
- Correlation of Expression of E-Cadherin, alpha-Catenin, beta-Catenin, and Clinicopathologic Parameters in Colorectal Adenocarcinomas.
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Hyoung Joong Kim, Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo
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Korean J Pathol. 2000;34(4):264-272.
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Abstract
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- The E-cadherin, alpha-catenin, and beta-catenin expressions were immunohistochemically investigated in paraffin-embedded materials of 80 cases of colorectal adenocarcinomas. The staining similar to normal colorectal mucosa with preserved strong membranous staining pattern was considered normal or preserved expression. The X2 test was used to analyse the statistical correlation of cadherin/catenin expression with clinicopathologic parameters and the Breslow test for the correlation with survival length. Normal colorectal mucosa showed strong membranous expression of cadherin/catenin complex. The reduced E-cadherin, alpha-catenin, and beta-catenin expression were found in 53/80 (66.3%), 46/80 (57.5%), and 44/80 (55.5%) cases of colorectal cancers examined, respectively. There were significant correlations between E- cadherin and alpha -catenin (p=0.035), and between alpha-catenin and beta-catenin (p=0.013). The reduced E-cadherin expression was associated with histologic dedifferentiation, tumor depth, lymph node metastasis, clinical stage (p<0.05), poor clinical outcome in stage II (p=0.016) and the reduced alpha-catenin expression with lymph node metastasis and clinical stage (p<0.05). Reduced expression of two or more proteins was correlated with lymph node matastasis, histologic dedifferentiation, clinical stage, and survival (p<0.05). The present study demonstrates a significant down-regulation of E-cadherin and alpha-catenin expression in colorectal cancer is associated with tumor invasiveness, histologic dedifferentiation, lymph node metastasis, and clinical stage. These results suggest that E-cadherin and alpha-catenin may be useful markers of invasiveness, lymph node metastatic potential, and clinical stage and of value as prognostic markers in the earlier stage. Further studies are needed to confirm the prognostic value of these cadherin/catenin complex.
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