Journal of Pathology and Translational Medicine

Original Articles

Expression of p53, c-myc, Transforming Growth Factor-alpha and -beta in Human Epithelial Ovarian Tumors.: Jae Hwa Lee, Young Ok Lee, Man Ha Huh; Korean J Pathol. 1996;30(1):23-31.

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Abstract PDF: 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.

Detection of bcl-2/IgH Gene Rearrangement and Expression of c-myc and p53 Oncoprotein in B-cell Lymphoma.: Ghee Young Kwon, Chul Woo Kim; Korean J Pathol. 1996;30(5):437-446.

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Abstract PDF: Many kinds of genetic changes have been known to be associated with malignant lymphoma and bcl-2, p53 and c-myc are some examples. We investigated the expression of p53 and c-myc protein in follicular and diffuse B cell lymphoma by immunohistochemistry to study the possible role of these proteins in the lymphomagenesis and transformation of the tumor. The rearrangement of bcl-2 oncogene and the immunoglobulin heavy chain gene was searched for in those cases by polymerase chain reaction(PCR). Paraffin-embedded tissues of fifteen follicular lymphomas and 14 diffuse lymphoma cases were used. The results of immunohistochemical staining are summarized as follows: 1) p53 positivity is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.001); 2) c-myc expression is not increased in diffuse lymphoma compared with follicular lymphoma; 3) PCNA index is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.03) but there was no statistically significant correlation between PCNA index and p53 positivity(P=0.44); 4) Eight out of 14 cases of follicular lymphoma and 12 of 14 cases of diffuse lymphoma showed rearrangement of the immunogloblulin heavy chain gene; 5) bcl-2 oncogene rearrangement was identified in only one case of follicular lymphoma and all the diffuse type lymphomas were negative in bcl-2/IgH rearrangement. In conclusion, assuming that the follicular pattern of B-cell lymphoma often transforms to diffuse type in later stages, c-myc over-expression might be an earlier event than p53 mutation in the process of tumor progression in B-cell lymphoma. bcl-2/IgH gene rearrangement in follicular lymphoma is a rare finding in Korea compared to that of Western countries.

Expression of bcl-2 and c-myc Proteins in Epidermal and Melanocytic Tumors.: Young Ha Oh, Chan Kum Park, Jung Dal Lee; Korean J Pathol. 1996;30(9):810-818.

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Abstract PDF: bcl-2 and c-myc protein expression were studied in 44 epidermal (8 seborrheic keratoses, 21 squamous cell carcinomas, and 15 basal cell carcinomas), and 26 melanocytic tumors(8 nevi, and malignant melanomas) by immunohistochemistry using the specific anti-bcl-2 and anti-c-myc monoclonal antibodies. 14 out of 15 basal cell carcinomas(BCC) (93.3%) showed expression of bcl-2 protein, 12 of which (85.7%) showed coexpression of c-myc protein. In the melanocytic tumors, 7 out of 8 nevi showed bcl-2 expression (87.5%). Five of these 7 cases (62.5%) also showed c-myc protein expression. Eight of 18 malignant melanomas(MM) (44.4%) showed expression of bcl-2 protein and 7 of these 8 cases (38.9%) also showed c-myc protein expression. All seborrheic keratoses and squamous cell carcinoma(SCC) were negative for bcl-2 proteins. 12 of 15 SCCs(80%) were positive for c-myc protein. In conclusion, bcl-2 and c-myc proteins were coexpressed in BCCs, nevi, and MMs. Coexpression of bcl-2 and c-myc proteins in these tumors was statistically significant(p<0.01), while no considerable differences of bcl-2 and c-myc expression were found between nevi and MMs. These results suggests that bcl-2 may cooperate with c-myc to promote tumorigenesis of BCCs, nevi, and MMs(p<0.01).

Microsatellite Instability and the Expression of Tumor-associated Genes in Multiple Cancer.: Kyung Soo Kim, Chan Choi, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1997;31(7):617-627.

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Abstract PDF: Genetic changes associated with oncogenes or tumor suppressor genes are frequently observed in human cancers. These changes may be more frequent in multiple primary cancers than sporadic cancers. These experiments were designed in order to know the genetic changes using microsatellite PCR technique and the expression of tumor-associated genes by immunohistochemistry for c-myc and p53 in 17 cases of multiple primary carcinomas. The niicrosatellite instability (MSI) were found in 8 of 17 cases (47.1 %); six cases showed MSI in more than two microsatellite loci and two cases revealed MSI in one locus. MSI was found in 2 out of 7.patients (28.6%) of multiple primary carcinomas arising from the unrelated organs, and 6 out of 10 patients (60.0%) arising from the same or related organs. When each case of multiple primary carcinomas was examined, immunohistochemistry for c-myc was positive in 25 cases (71.4%) and p53 was positive in 21 cases (60.0%) out of 35 cases. But there was no correlation between MSI and expression of tumor-associated genes. From the above the results, MSI is more important in carcinogenesis of multiple primary carcinomas arising from the same or related organs than those from unrelated organs.

Detection of the c-m c Oncogene Amplification in Ovarian Carcinomas by Differential Polymerase Chain Reaction.: Geun Shin Lyu, Chan Kum Park, Chun Geun Lee, Youl Hee Cho, Youn Yeoung Hwang, Jung Dal Lee; Korean J Pathol. 1997;31(7):644-654.

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Abstract PDF: The amplification of c-myc oncogene was evaluated in 42 cases of ovarian carcinomas to correlate with clinical parameters. Using oligonucleotide primers, sequences from the c-myc exon-3 gene and from a control gene, tissue plasminogen activator (tPA), were amplified simultaneously by polymerase chain reaction (PCR). After the products of differential PCR (d-PCR) were electrophoresed, slot blot hybridization was performed, and hybridized with P32 dATP-labeled myc and tPA oligonucleotide probes and then autoradiographed. The signal intensities of the two products were quantitated by densitometry and the ratios of two products (c-myc/tPA) were measured. The ovarian carcinomas showed significantly increased amplification of c-myc oncogene Oligonucleoti compared to normal control group (p<0.05). 15 of 42 cases (35.7%) showed various degrees of the MYC gene amplification up to 27 folds in various histologic types of ovarian carcinomas. No significant differences of the MYC gene amplification according to histologic subtypes, tumor action) grades and clinical stages of ovarian carcinomas were present.

Expression of c-erbB-2, c-myc, c-fos, bcl-2, p53, PCNA, and TGF-alpha in Transitional Cell Carcinoma of the Urinary Bladder.: Keun Hong Kee, Yoon Kyeong Oh; Korean J Pathol. 2000;34(7):516-523.

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Abstract PDF: Most of malignant tumors in the urinary bladder is transitional cell carcinoma (TCC) deriving from the urothelium. Clinical stage and histopathologic grading of the TCC of the urinary bladder is important in the determination of the patient's prognosis. To investigate the correlation between the prognostic factors and the expression of the various oncoproteins and growth factors in each grade of the TCC, immunohistochemical stains for c-erbB2, c-myc, c-fos, bcl-2, p53, proliferating cell nuclear antigen (PCNA), and transforming growth factor-alpha (TGF-alpha) were performed in the formalin fixed paraffin embedded tissues of the TCC (Grade I; 15 cases, Grade II; 20 cases, Grade III; 15 cases) of the urinary bladder. The immunoexpression rate of c-erbB2 was immunoexpression 78.0% in the grade I, 85.0% in the grade II, and 95.0% in the grade III TCC. The immunoexpression rate of c-myc, c-fos and bcl-2 was below 5% in each grades of TCC. The p53 immunoexpression was identified in 11.5%, 24.3% and 30.6% of the grade I, II, and III TCC, respectively. The PCNA and TGF-alpha expression was 53.0% and 27.6% in the grade I, 77.3% and 32.7% in the grade II, and 78.2% and 37.3% in the grade III TCC, respectively. These results suggest that the expressions of c-myc, c-fos, bcl-2, and TGF-alpha are similar in each grade of the TCC and the positivity of c-erbB2, p53, and PCNA shows an increasing tendency for the higher grade TCC of the urinary bladder. Therefore, c-erbB2, p53, and PCNA are clinically useful predictors of the patient's prognosis.

Significance of p53, cyclin D1 and c-myc Expressions in Thyroid Tumors.: Zhuhu Li, Ho Jong Jeon, Mi Ja Lee; Korean J Pathol. 2004;38(1):29-34.

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Abstract PDF: BACKGROUND
The G1/S phase proteins of the cell cycle play critical roles in tumorigenesis and tumor progression. Our aim was to investigate the significance of p53, cyclin D1 and c-myc expressions in thyroid tumors.
METHODS
The expressions of these proteins were examined in 217 cases of thyroid tumors and tissues using immunohistochemistry. The results were correlated with lymph node metastasis.
RESULTS
p53 expression was seen in 75.5, 47.5, 66.7, and 50% of papillary carcinomas (PC), follicular carcinomas (FC), undifferentiated carcinomas (UC) and follicular adenomas (FA), respectively. There was a significant difference between these expressions in these tumors and the results in nodular hyperplasia (NH) and normal tissues. Cyclin D1 expression was noted in 80.0, 68.4, 66.7, 61.1 and 79.5% of PC, FC, UC, FA and NH, respectively. c-myc expression was seen in 80.0, 94.2, 66.7, 66.7 and 52.3% of PC, FC, UC, FA and NH, respectively. There was a significant association between the expressions in these tumors and the results in normal tissues. The expressions of p53, cyclin D1 and c-myc were not correlated with lymph node metastasis.
CONCLUSIONS
These findings suggest the expressions of p53, cyclin D1 and c-myc may act in the early stage, and participates in tumorigenesis and promoting cell growth.

Expression of Cellular Oncogenes in Gastric Carcinoma Related with Its Histologic Subtype: Southern blot analysis and immunohistochemistry.: Jin Sook Jeong, In Hoo Kim; Korean J Pathol. 1992;26(6):543-551.

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Abstract PDF: To search biologic characteristics of gastric carcinoma, one of the most common cancer in Korea, the author examined the alterations in DNA level and the expression of Ha-ras gene and c-myc gene in 20 primary tumors. Amplification of c-Ha-ras DNA was detected in 4(40%) of 10 patients who showed histologic subtype of relatively differentiated adenocarcinoma, but rearrangement of c-Ha-ras DNA was absent. Neither augumentation nor deletion of the c-myc DNA was observed. Higher expression of the ras p21 in tumor cells was noted in more differentiated tumor cells rather than poorly differentiated cases. One mucinous carcinoma, two signet ring cell carcinomas and one papillary carcinoma did not disclose expression of p21. The expressions of c-myc oncogene product were variable and were not correspond to the expressions of ras p21. A tendency that poorly differentiated tumor cells had higher expression of c-myc oncogene was suggested.

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