Journal of Pathology and Translational Medicine

Original Articles

Expression of p53 Protein and c-erbB-2 Oncoprotein in Breast Carcinoma.: Eun Hee Lee, Dong Sug Kim, Tae Sook Lee, Soo Jung Lee; Korean J Pathol. 1995;29(5):596-606.

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Abstract: This study was conducted to evaluate the expression of p53 and c-erbB-2 using immuno-histochemical methods in 145 primary breast carcinomas and to correlate it with other histo-pathological prognostic factors. Invasive ductal carcinoma represented 129 of the cases. Expression of p53 protein and c-erbB-2 oncoprotein was present in 48% (62/129) and 30% (39/129) of invasive ductal carcinomas, respectively. The expression of p53 protein was stongly associated with a high score of degree of differentiation (p<0.05), nuclear pleomorphism (p<0.05), mitotic index (p<0.05), SBR grade (p<0.05) and MSBR grade (p<0.05), but it was not associated with patient's age, size of tumor or axillary node metastasis. The overexpression of c-erbB-2 C-erbB-2 oncoprotein was strongly associated with a high score of nuclear pleomorphism and a high SBR grade (p<0.05), but not associated with patient's age, size of tumor, axillary node metastasis, degree of differentiation, mitotic index or MSBR grade. An inverse relationship between the expression of p53 protein and estrogen receptor status was found, but the expression of c-erbB-2 was not associated with estrogen receptor status. It is concluded that p53 protein and c-erbB-2 oncoprotein are important prognostic factors in breast cancers, and that the aberrant expression of p53 protein is the most useful prognostic factor becausd of strong association of known histopathological prognostic factors and negative estrogen receptor status.

c-erbB-2 Oncoprotein Expression in Ductal Carcinoma in situ and Paget's Disease of the Breast.: Jung Yeon Kim, Kyung Ja Cho, Seung Sook Lee, Shin Kwang Khang, Nam Sun Paik; Korean J Pathol. 1996;30(11):972-980.

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Abstract PDF: A clinico-pathologic study with an immunohistochemical examination for c-erbB-2 expression in 54 cases of ductal carcinoma in situ and 16 cases of Paget's disease of the breast was performed. c-erbB-2 oncoprotein overexpression was observed in 45% (24/54) and 88% (14/16) of ductal carcinoma in situ and Paget's disease, respectively. The overexpression of c-erbB-2 oncoprotein was significantly correlated with the nuclear grade of tumors and inversely with the status of the estrogen receptor. c-erbB-2 was positive in 4 out of 5 patients with metastasis to axillary lymph nodes and 3 out of 4 patients who died of the disease. Prognostic significance of c-erbB-2 oncoprotein in ductal carcinoma in situ was highly suggested. The expression of c-erbB-2 oncoprotein in Paget's disease was well correlated with coexisting infiltrating or in situ ductal carcinoma. The high positive rate of c-erbB-2 oncoprotein in ductal carcinoma with Paget's disease could be understood with a recent hypothesis that c-erbB-2 oncoprotein is involved in promotion of cell motility and the spread of carcinoma cells.

A Study on the DNA Ploidy and Expression of c-erbB-2 Oncogen in the Ovarian Carcinomas.: Jong Jae Jung, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1997;31(1):15-22.

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Abstract PDF: To evaluate the relationships among the c-erbB-2 oncogene expression, DNA ploidy and other prognostic factors, an immunohistochemical study of the c-erbB-2 oncogene product and flow cytometric analysis of DNA ploidy were performed in paraffin sections of 42 cases of ovarian carcinomas. The results were as follows: 1) The positive reaction for c-erbB-2 oncogene product was observed mainly along the cytoplasmic membrane, and occasionally within the cytoplasm of the tumor cells. 2) Overall the positivity of c-erbB-2 oncogene expression was 45.2% of the ovarian carcinomas. By the histological types, the positivity was 35.7% in serous carcinoma, 80.0% in mucinous carcinoma, and 45.2% in endometrioid carcinoma; by the degree of differentiation, 57.1% in well differentiated carcinoma, 40.0% in moderately differentiated, and 27.3% in poorly differentiated; by the nuclear grading, 58.3% in grade I, 52.6% in grade II, and 18.2 % in grade III; and by the clinical staging, 57.1% in stage I, 42.8% in stage II, and 35.0% in stage III. The expression of the c-erbB-2 oncogene in the ovarian carcinomas was higher in the tumors of good differentiation, of the lower nuclear grade and of the lower clinical stage. 3) The incidence of DNA aneuploidy in the cases positive for the c-erbB-2 oncogene expression(47.3%) was higher than that in the negative cases(31.4%). From the above results, therefore, it is suggested that the c-erbB-2 oncogene may be involved in the early stage of ovarian carcinogenesis. Also suggested is that ovarian carcinomas positive for the c-erbB-2 oncogene in the early stages may have higher probability of having a DNA aneuploid cell line during the progress of the tumors.

Expressions of Epidermal Growth Factor Receptor, c-erbB-2 and p53 Protein as Useful Markers of Malignant Potential in a Transitional Cell Carcinoma of the Urinary Bladder.: Gu Kong, Ki Yong Shin, Sun Jin Kim, Young Hyeh Ko, Hae Young Park, Young Nam Woo, Jung Dal Lee; Korean J Pathol. 1997;31(1):51-58.

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Abstract PDF: Transitional cell carcinoma(TCC) of the urinary bladder shows marked heterogeneity in biological behaviors. Evidence has accumulated that biological markers may provide significant information to predict the potential aggressiveness of TCC. We have assessed the expression of the epidermal growth factor receptor (EGF-R), c-erbB-2 and p53 proteins in 56 cases of TCC to investigate the prognostic significance of differential expression of these oncoproteins using an immunohistochemical method. We analysed the expression patterns of these oncoproteins according to tumor stage and grade. And we assessed the probability of progression-free survival in stage T1 tumors according to their expressions. Positive rates of EGF-R (>+3 staining intensity), c-erbB-2 (intense membrane staining) and p53 proteins (>20% positive cells) were 73.2%, 37.5% and 42.9%, respectively. Invasive tumors had significantly higher positive rates of all three factors than did superficial tumors (p<0.005 for EGF-R and c-erbB-2, p<0.05 for p53). High grade tumors had significantly higher positive rates of c-erbB-2 and p53 proteins (p<0.005). In superficial tumors, T1 tumors had higher positive rate of p53 protein compared with Ta tumors (p<0.05). Twelve cases of superficial tumors (34.3%) were positive for EGF-R and negative for c-erbB-2 and p53 proteins. Nine cases of superficial tumors(25.7%) were negative for all three factors. In invasive tumors, however, 42.5% of the cases were positive for all three factors. The overexpression of p53 protein was the only useful marker to predict the rapid progression in stage T1 tumors (p<0.05, log-rank test). These results suggest that the differential overexpression of EGF-R, c-erbB-2 and p53 proteins could be useful to depict tumor aggressiveness of TCC of the urinary bladder. And, the overexpression of a p53 protein may be a useful marker to predict the possibility of rapid progression in stage T1 tumors.

A Comparative Study of Immunohistochemical Expression of p53, bcl-2, c-erbB-2, and MIB-1 in Polypoid and Infiltrative Colorectal Carcinomas.: Jeong Seok Moon, Seong Hwan Park, Bong Kyong Shin, Ju Han Lee, Joon Ho Shin, Bom Woo Yeom; Korean J Pathol. 1998;32(8):581-589.

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Abstract: Almost all colorectal carcinomas have been thought to develop from pre-existing adenomas. However, some colorectal carcinomas can arise directly from normal flat mucosa, and usually form infiltrative mass at the early stage. The carcinogenesis of this infiltrative carcinoma may be different from the well-known adenoma-carcinoma sequence, which usually forms a polypoid mass. The purpose of this study is to investigate the different expression of various oncogenes in polypoid carcinoma and infiltrative carcinoma. We performed immunohistochemical staining on p53, bcl-2, c-erbB-2 and MIB-1 in 29 polypoid carcinomas arised from adenomas, and 21 infiltrative carcinomas. The average tumor size of infiltrative carcinomas (5.5 cm) was larger than that of polypoid carcinomas (3.1 cm), and the polypoid carcinomas were differentiated more than the infiltrative carcinomas. The results of p53, bcl-2, c-erbB-2, and MIB-1 antisera immunoreactivity in the polypoid carcinoma were 79%, 17%, 21%, and 100%, and those in the infiltrative carcinoma were 71%, 29%, 29%, and 100%, respectively. However the diffuse positivities of p53 and MIB-1 antisera were slightly higher in the infiltraive carcinomas (62%, 76%) than in the polypoid carcinomas (55%, 41%) (p=0.63, 0.01). And the results of p53 and c-erbB-2 immunoreactivity in the adenomas were 52% and 17%, respectively, which is significantly lower than that in the polypoid carcinoma(p=0.03, 0.74). The immunoreactivty of bcl-2 in the adenoma was 72%, which was significantly higher than that in the polypoid carcinoma (17%) (p<0.01). In summary, we did not show the significant difference in expression of p53, bcl-2, c-erbB-2, and MIB-1 proteins between polypoid and infiltrative carcinomas. However, the tendency of infiltrative carcinomas having a more aggressive nature suggests another carcinogenetic mechanism is involved in the colorectal carcinogenesis.

Immunohistochemical Characteristics of Biliary Tract Carcinoma and Its Precancerous Lesions.: Jiyoung Kim, Youngnyun Park, Hogeun Kim; Korean J Pathol. 1998;32(11):985-992.

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Abstract: Carcinomas of the biliary tract are known to be more common in East Asia than in Western countries, but their exact histopathological characteristics and tumorigenesis are not well elucidated. To examine the histological and immunohistochemical characteristics of the biliary tract carcinomas according to their anatomical sites and to elucidate their tumorigenesis, we performed histological review and immunohistochemical study in a total of 135 cases of biliary tract carcinomas; 24 intrahepatic bile duct, 34 gallbladder, 51 common bile duct, and 26 periampullary carcinomas. Precancerous lesions were associated with 5 (20.8%) cases of intrahepatic duct carcinomas (dysplasia 5), 7 (20.6%) cases of gallbladder carcinomas (adenoma 5, dysplasia 2), 10 (19.6%) cases of common bile duct carcinomas (adenoma 7, dysplasia 3), and 2(7.7%)cases of periampullary carcinomas (adenoma 2). Immunohistochemically, c-erbB-2 expression in gallbladder carcinoma (21/34, 62%) was significantly higher than that of intrahepatic (8/24, 33%). Ki-67 indices were higher in common bile duct carcinomas (19%) than those of intrahepatic bile duct (14%) or periampullary carcinomas (12%). Overexpression of p53 gene product in the periampullary carcinomas (20/22, 77%) was higher than that of intrahepatic (12/24, 50%) or common bile duct carcinoma (26/51, 51%). In the precancerous lesions the c-erbB-2 expression was present in 29% of the gallbladder, 20% of the intrahepatic, 10% of the common bile duct precancerous lesions and none of the 2 cases of adenomas in the periampullary region. The p53 overexpression in the precancerous lesions was frequent, ranging from 43% to 60%. These results suggest that a mechanism involving p53 gene mutation and c-erbB-2 gene activation is present in the tumorigenesis in a significant number of the biliary tract carcinomas and they may be the early events in the tumorigenesis of the biliary tract carcinomas.

The Expression of p53, c-erbB-2 and nm23 Proteins in Breast Cancer.: Kyo Young Lee, Yong Goo Kim, Young Shin Kim, Kyung Ja Han, Chang Suk Kang, Jean A Kim, Won Il Kim, Sang In Shim; Korean J Pathol. 1999;33(2):88-95.

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Abstract: Recently, p53, c-erbB-2 and nm23 proteins have been studied in breast cancer. The expression of p53 protein indicates the mutation of p53 gene known as a tumor supressor gene, and c-erbB-2 gene amplification has been considered an indicator of poor prognosis and nm23 a metastsis suppressor gene. In order to elucidate the roles and relations of these proteins in the develpoment, progression and metastasis in breast cancer, we studied 89 cases of invasive breast cancer and 32 cases of lymph node metastasis for the expression of p53, c-erbB-2 and nm23 proteins using an immunohistochemical method. The results were as follows: 1) The expression rates of p53, c-erbB-2, and nm23 proteins in breast cancer were 40.4%, 34.8% and 55.1%, respectively. Co-expression of p53 protein and c-erbB-2 protein was found in 20.2% of cases, showing the highest incidence in poorly differentiated type (40%). 2) p53 protein expression was increased in poorly differentiated type but was not statistically significant. On the other hand, the expression of nm23 protein was decreased in poorly differentiated type, which was statistically significant (p<0.05). 3) The correlation of p53 protein expression with c-erbB-2 protein expression was statistically significant (p<0.05) but that with nm23 protein was not. 4) In the cases with lymph node metastasis, discordant expression of p53, c-erbB-2 and nm23 proteins between primary tumor and the lymph node metastatic tumor was found in 9.4%, 3.1% and 18.8% of cases, respectively. The above results suggest that overexpression of p53 and c-erbB-2 proteins and downregulation of nm23 protein are associated with the tumor progression in the breast cancer.

Expression of Epidermal Growth Factor Related Peptides, EGF-R, and c-erbB-2 and Their Relationship with the Prognostic Factors in Gastric Carcinoma.: Joo Heon Kim, Jin Wook Lee, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee; Korean J Pathol. 1999;33(11):1039-1046.

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Abstract PDF: 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 c-erbB-2 and Cyclooxygenase-2 in Pancreatic Ductal Adenocarcinoma.: Hye Jeong Choi, Hong Jin Kim, Sung Soo Yun, Joon Hyuck Choi; Korean J Pathol. 2007;41(3):171-175.

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Abstract PDF: Background
: Carcinoma of the pancreas is a fatal malignant disease with limited therapeutic options. Cyclooxygenase-2 (COX-2) and c-erbB-2 are known to be involved in the carcinogenesis, differentiation and invasiveness of various neoplasms. We studied the immunohistochemical expressions of c-erbB-2 and COX-2 and the correlation between these expressions and the clinicopathologic parameters and the relation between the expressions.
Methods
: Immunohistochemical staining for c-erbB-2 and COX-2 were performed on the paraffin embedded sections of 36 cases of surgically resected ductal adenocarcinoma of the pancreas and 10 cases of non-neoplastic pancreas tissue.
Results
: The non-neoplastic control group showed a c-erbB-2 expression in the acini (8/10) and ducts (2/10), and a COX-2 expression in the acini (6/10) and ducts (3/10). The overexpression of c-erbB-2 was observed in 58% (21/36) of the carcinoma specimens. No significant correlation was found between c-erbB-2 and age, gender, tumor size, gross type, histologic grade, vascular invasion, perineural invasion, lymph node metastasis, and the TNM stage. The overexpression of COX-2 was observed in 41.7% (15/36) of the carcinoma specimens. The COX-2 expression was significantly high in the lymph node metastasis group (p<0.05), but it was not correlated with the other clinicopathologic parameters. Also there was no significant correlation between the c-erbB-2 and COX-2 expressions.
Conclusions
: In pancreatic ductal adenocarcinomas, c-erbB-2 and COX-2 were frequently overexpressed, and COX-2 overexpression was correlated with lymph node metastasis.

Fascin-1 Protein Expression in Gastric Carcinoma.: Seoung Wan Chae, Jin Hee Sohn; Korean J Pathol. 2006;40(2):112-117.

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Abstract PDF: BACKGROUND
Fascin-1 is a globular cross-linking and actin bundling protein that provides mechanical support to cellular protrusions and cell motility. The expression of fascin in epithelial neoplasms has been recently reported, but its exact mechanism in cancer is unknown. The purpose of this study was to assess the expression of fascin and its relationship with the clinicopathologic parameters and the other tumor markers in gastric carcinoma.
METHODS
Immunohistochemical stainings for fascin, c-erbB-2, p53 and Ki-67 labeling index were performed in 62 gastric carcinoma specimens.
RESULTS
Fascin-1 protein was not expressed in the normal gastric glandular epithelial cells. It had an expression in 35.5% of the gastric adenocarcinomas. The fascin-1 expression in carcinoma was slightly increased in the well to moderately differentiated tumors compared with the poorly differentiated tumors. The fascin-1 expression was correlated with the c-erbB-2 protein expression. There was no significant correlation with the clinicopathologic factors such as tumor size, nodal metastasis, pathologic stage, p53 protein expression and Ki-67 labeling index.
CONCLUSIONS
This study reveals the possibility that the fascin-1 protein expression in gastric carcinoma may be closely linked with the c-erbB-2 protein expression. However, further study on fascin-1 and c-erbB-2 protein at the cellular level and their clinical relevance is needed.

A Study of the Correlation between Expression of c-erbB-2 Oncoprotein and Various Clinicopathological Prognostic Factors in Breast Carcinoma.: Jong Hee Nam, Kyung Soo Kim, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1995;29(2):136-144.

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Abstract PDF: Immunohistochemical study for c-erbB-2 oncoprotein was performed on paraffin sections of 76 primary breast carcinomas to determine the relationship between expression of c-erbB-2 and various clinicopathological prognostic indicators, including the expression of epidermal growth factor receptor (EGFR). Positive reaction for c-erbB-2 oncoprotein revealed an intense red granular staining predominantly located at the tumor cell membrane, with some cells exhibiting a weak cytoplasmic staining as well. The epithelial cells of the normal lobule and duct showed a negative reaction. Positive reaction for EGFR revealed a granular staining in the cytoplasm and the cell membrane of the tumor cells. Some tumors showed a positive EGFR staining in the epithelial cells of normal duct and lobule. Twenty six of 76 cases (34.2%) of primary breast carcinomas revealed a positive reaction for c-erbB-2 oncoprotein, and 28 cases (36.8%) were positive for EGFR. Expression of c-erbB-2 oncoprotein and EGFR was evident in 37.7% and 40.6% of 69 classic invasive ductal carcinomas, respectively. None of the other histological types showed a positive reaction. Expression of c-erbB-2 oncoprotein was strongly associated with tumor size(p=0.0015), histologic grade(.p=0.0175), vascular invasion(p=0.0043), and lymph node metastasis(p=0.0024), but not with age at diagnosis(p=0.1836). No significant association was found between expression of c-erbB-2 oncoprotein and EGFR. Co-expression of c-erbB-2 oncoprotein and EGFR was also strongly associated with tumor size (p=0.0029). These results suggest that c-erbB-2 oncoprotein is biologically distinct from EGFR, and may be used as a prognostic indicator of breast carcinoma due to its strong association with various clinicopathological prognostic factors.

c-erbB-2 Oncoprotein Overexpression in Breast Cancer.: Tae Sook Hwang, Kyung Ja Cho, Young Bae Kim, Joo Ryung Huh, Ja June Jang; Korean J Pathol. 1994;28(1):1-7.

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Abstract PDF: c-erbB-2 oncogene is a normal cellular proto-oncogene coding transmembrane glycoprotein structurally similar to the epidermal growth factor receptor. Amplification of this oncogene in a variety of human adenocarcinomas has been reported and is particularly well documented in breast carcinoma. It has been suggested that amplification of this oncogene is indicative of poor prognosis and is valuable only second to the lymph node status. Using immunohistochemical staining for the c-erbB-2 protein, overexpression of this protein was analysed in 228 primary breast cancer specimens and the frequency of overexpression and the relationship between overexpression and the other established prognostic variables are evaluated. Ninty three cases out of 228 cases(40.8%) show postive oncoprotein overexpression and using the chi-squared test for a trend, a significant correlation was found between c-erbB-2 protein staining and the histological grade, lymph node status, and estrogen receptor status(P<0.05). No significant association was found between staining and the patient's age and tumor size. Most of the tumors with histological types known to have good prognosis showed negative expression. Above findings strongly suggest that expression of c-erbB-2 oncogene is another independent indicator of poor prognosis in breast carcinoma.

Correlation between Expression of c-erbB-2 Oncogene and Various Prognostic Factors in the Colorectal Carcinoma.: Wan Kim, Hong Ran Choi, Ji Shin Lee, Jong Tae Park, Chang Soo Park, Kyu Hyuk Cho; Korean J Pathol. 1993;27(3):217-225.

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Abstract PDF: The c-erbB-2 oncogene, which is a new human proto-oncogene similar to EGFR structurally, generates a glycoprotein of tyrosine kinase family with a molecular weight of 185,000 To evaluate the prognostic significance of c-erbB-2 oncogene expression in colorectal carcinoma, We analysed 73 colorectal carcinomas in paraffin sections immunohistochemically, using the monoclonal antibody specific for the c-erbB-2 oncogene product and correlated with clinicopathological data. The results were as follows 1) The immunoreactivity for c-erbB-2 oncogene was localized to cell membrane of the tumor cells and occasionally observed within the cytoplasm. 2) The positivity of c-erbB-2 oncogene expression was 71.2%(52/73) of the colorectal carcinomas overall. According to the histological types, the positivity of c-erbB-2 oncogene in adenocarcinoma(77.4%) was higher than that in mucinous carcinoma(36.4%)(p<0.05). 3) Expression of c-erbB-2 oncogene was significantly correlated with lymph node metastasis or distant metastasis(p=0.0117), Dukes stage(p=0.0432), and TNM classification(p=0.0102). These results suggest that c-erbB-2 oncogene expression may be used as a prognostic factor of colorectal carcinoma because of its correlation with other clinicopathological prognostic factors.

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