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Original Articles
- Immunohistochemical Investigation on Expression of Hepatitis B Surface Antigen, Transforming Growth Factor-alpha, and Proliferating Cell Nuclear Antigen in Hepatocellular Carcinoma.
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Bang Hur, Man Ha Hur
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Korean J Pathol. 1995;29(4):478-491.
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Abstract
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- In an attempt to evaluate the expression of hepatitis B surface antigen(HBs Ag), transforming growth factor-ct(TGF-alpha), and proliferating cell nuclear antigen(PCNA) in hepatocellular carcinoma(HCC), an immunohistochemical investigation(ABC method) was performed using 31 surgically resected HCCS. The authors examined the expression rate and patterns, histopathologic correlation, and inter-relationships among these expressions. The results were summarized as follows. 1) Among 25 seropositive HCCS, 15 cases showed tissue expression of HBs Ag(60.0%), being expressed as a predominantly cytoplasmic pattern. Its expression rate in low grade HCC was significantly high(76.9%), in contrast to a low rate in high grade HCC(41.7%)(P<0.05). Adjacent nonenoplatic tissue showed a higher expression rate(82.6%). 2) TGF-alpha was expressed in 23 of 31 cases of HCC(74.3%). The intensity and extent of its expression did not correlate tyros with histopathologic features. Bile duct epithelium, juxtaposed and/or entrapped liver cells, and cirrhotic nodules were variably expressed, of which intense peripheral reaction within the nodules was frequently noted. 3) PCNA was expressed throughout the neoplastic tissue of HCC. Its index was significantly high(34.4 13.6), being compared to low index index(3.5 2. 1) in the nonneoplastic tissue(P<0.005). High grade tumors revealed a higher index than the low grade tumors(P<0.05).
Conclusively, this data confirms that PCNA index offers useful information about cell proliferation associated with histologic degrees of malignancy of HCC, albeit TGF-alpha is also involved in cellular proliferation of both liver cell and bile duct epithelium. Changes in incidence and cellular localization of HBs Ag expression between the neoplastic and nonneoplastic tissues suggest that an integrated viral genome could be functionally altered during hepatocarcinogenesis. A significant inter-relationship among these expressions was not observed.
- Expression of p53, c-myc, Transforming Growth Factor-alpha and -beta in Human Epithelial Ovarian Tumors.
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Jae Hwa Lee, Young Ok Lee, Man Ha Huh
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Korean J Pathol. 1996;30(1):23-31.
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Abstract
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- The author examined expression of tumor-related antigens, such as p53 tumor supressor protein, c-myc, TGF-alpha, and TGF-beta proteins in 75 cases of surgically resected epithelial ovarian tumors. Peroxidase immunohistochemistry was used to determine the frequency of expression, the relationship among expression of these antigens and histopathological spectrums, and clinical stage, and their potential prognostic significance. The results are summarized as follows. A positive correlation was found between expression of p53(P=0.02), c-myc(P=0.03), and TGF-alpha(P=0.001) and histological degrees of malignancy(benign, borderline, or malignant) in epithelial ovarian tumors. A significant correlation was found between expression of p53 and histological degrees of malignancy in serous ovarian tumors(P=0.003) and mucinous tumors (P=0.049). A significant correlation was also found between expression of c-myc and the histological grade of serous carcinomas(P=0.02). A correlation between expression of these antigenic proteins and clinical stage of epithelial ovarian tumors was not demonstrated. Expression of p53 and c-myc was closely correlated with expression of TGF-alpha irrespective of the histological degrees of malignancy and type of epithelial ovarian tumors(0.4 < or = K < or = 0.7).
The results of this study support the ideas that expression of c-myc and TGF-alpha might be a useful prognostic indicator in human ovarian carcinomas, and expression of p53 could be another indicator of prognosis, as the expression of p53 is characteristic in that the expression is mostly seen in invasive ovarian carcinomas.
- Expressions of the Tumor Associated Proteins and Their Correlation with the Pathologic Features in Childhood Hepatoblastoma.
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Han Seong Kim, Hyo Seop Ahn, Kwi Won Park, Ja June Jang
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Korean J Pathol. 1997;31(6):538-545.
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Abstract
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- Hepatoblastoma is a rare malignant liver tumor found in children. Its biological characteristics and prognostic factors have not been well known. We investigated 29 cases of hepatoblastoma, registered in university hospitals in Seoul from 1984 to 1996. By the immunohistochemical method, p53, Waf-1 (p21), bcl-2, heat shock protein 70 (hsp70), c-jun, transforming growth factor-alpha (TGF-alpha) expressions were studied. Those data were compared with clinico-pathologic features; age, sex, tumor size, tumor stage and histologic subtypes. Expression of p53 and bcl-2 were each observed separately in single cases. Expression of c-jun was more frequently noted in patients at higher stages. Expression of TGF-alpha decreased in the order of pure fetal, mixed, embryonal and small cell anaplastic subtypes. Cumulative survival rate was lower in females than in males and in patients with a higher tumor stage.
According to histologic subtypes, survival rates decreased in the order of pure fetal, mixed, embryonal and small cell anaplastic subtypes. Survival rate was lower in patients with c-jun expression. Group of TGF-alpha labelling index under 19 showed a lower survival rate than that over 19. In conclusion, we found that tumor associated proteins, c-jun and TGF-alpha, are closely related to the prognosis of hepatoblastoma but p53 and bcl-2 may not be related to it.
- The Effects of Transforming Growth Factor beta1 on Apoptosis in Rat Hepatocellular Carcinoma.
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Young Euy Park, Young Hee Choi, Won Yo Lee, Jin Ja Park, Kyung Chan Choi, Hyung Shik Shin
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Korean J Pathol. 1999;33(2):71-79.
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Abstract
- Based upon the concept that carcinogenesis is associated with apoptosis, specific therapies designed to enhance the susceptibility of cancer cells to undergo apoptosis could be developed. Thus, in this paper, it was designed to investigate whether, using rat animal model with chemical-induced hepatocellular carcinoma, TGF-1 in vivo could induce apoptosis in cancer. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into group A treated with the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-Acetaminofluorene (AAF), group B TGF-, group C TGF-1, and group D adriamycin after hepatocellular carcinoma developed. For detection of apoptotic cells, apoptotic indices were examined by the in situ end DNA labelling method. The expression of proliferating cell nuclear antigen was examined by immunohistochemical staining. Apoptosis of rat hepatocellular carcinoma cells increased significantly to 4.92+/-2.32/HPF in the group C compared with the control group (A) (2.54+/-1.13/HPF; P<0.05). Two distinctly different populations of proliferating hepatocellular carcinoma cells were identified. The cells at G1/S boundary (weak granular staining) increased to 15.75+/-6.19/HPF and 6.45+/-2.93/HPF in the groups C and D, respectively, but decreased to 2.42+/-2.06/HPF in the group B compared with the control group (A) (6.38+/-2.18/HPF; p<0.05). The cells at S phase (strong granular staining) increased to 3.37+/-2.69/HPF in the group B but decreased to 0.32+/-0.47/HPF in the group D (p<0.05). In conclusion, these results indicate that the TGF-1 may be used as an effective anticancer agent.
- Expression of Epidermal Growth Factor Related Peptides, EGF-R, and c-erbB-2 and Their Relationship with the Prognostic Factors in Gastric Carcinoma.
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Joo Heon Kim, Jin Wook Lee, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee
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Korean J Pathol. 1999;33(11):1039-1046.
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- Recent investigations have revealed that autocrine growth factors and their receptors are closely related and play an important role in controlling cancer cell growth. We performed an immunohistochemical study on the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R), c-erbB-2, and PCNA labelling index in 60 cases of human gastric carcinomas. TGF-alpha was detected in 38 cases (63.3%), EGF in 26 cases (43.3%), EGF-R in 44 cases (73.3%), and c-erbB-2 in 18 cases (30%). These growth factors, EGF-R and c-erbB-2, were found more often in advanced gastric cancers. The PCNA labeling index was significantly higher in tumors with the expression of EGF-R or c-erbB-2. Tumors with simultaneous expression of EGF, TGF-alpha, EGF-R and c-erbB-2 was associated with a high PCNA labeling index. A correlation was observed between the synchronous expression of growth factors and its receptors and histological differentiation. The results suggest that the expression of EGF, TGF-alpha, EGF-R and c-erbB-2 are closely related and plays an important role in the growth and progression of human gastric carcinoma.
- Expression of Trans forming Growth Factor-a and Proliferating Cell Nuclear Antigen in Human Gliomas.
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Gyeong Sin Lee, Byung Hyun Kim, Bong Kwon Chun, Man Ha Huh
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Korean J Pathol. 1994;28(2):149-153.
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- To evaluate the expression of transforming growth factor-alpha(TGF-alpha) and proliferating cell nuclear antigen(PCNA) and its relation to the differentiation of the tumors, immunohistochemical studies were performed in 49 human gliomas. Tumors were graded by a 3-grade-system; grade I=low grade glioma, grade Il=anaplastic glioma, grade III=glioblastoma multiforme. TGF-A and PCNA were predominantly expressed in malignant gliomas compared with benign gliomas. Malignant gliomas revealed 87% TGF-A reactivity, while benign gliomas revealed 26% TGF-A reactivity. The proliferation index with PCNA was 26%+/-7%(mean+/-standard deviation) in malignant gliomas and 5%?% in benign gliomas. A strong positive correlation between tumor grade and extent of TGF-A and PCNA expression was found(P<0.0001, Chi square and P<0.002, T-test).
Synchronous expression of TGF-A and PCNA was observed in 16 cases(33%). The results of this study support the suggestion that the expression of TGF-A might be a useful prognostic indicator in human gliomas.
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