Journal of Pathology and Translational Medicine

Original Articles

Microvessel Quantification, Expression of p53 Protein and MIB-1 in Colorectal Adenoma and Carcinoma.: Tae Jung Jang, Jung Ran Kim, Han Ik Bae; Korean J Pathol. 1997;31(1):40-50.

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Abstract PDF: Angiogenesis is a crucial step in tumor growth and progression. Scarce data is available on angiogensis in gastrointestinal tumors. We studied 16 normal colon, 44 adenomas and 29 carcinomas to evaluate angiogenesis in colorectal tumors and to assess the correlation among p53 protein, proliferative activity and other clinical prognostic parameters. Endothelial cells were immunostained with an anti-Factor VIII mAb; in each case three microscopic fields(x 200) were counted: average number of the three fields was defined as microvessel density (MVD). p53 protein expression was 45.5%(20/44) in adenomas, and 79.3%(23/29) in carcinomas (p<0.01). p53 protein expression of carcinomas was 57.1%(4/7) in diploid tumors, 100%(8/8) in aneuploid tumors (p=0.07), 100%(8/8) in well differentiated tumors, and 50%(2/4) in poorly differentiated tumors (p=0.09). MIB-1 score was 2.3+/-0.7(38) in adenomas, 3.4+/-0.5(29) in carcinomas (p<0.01). There was no significant correlation between p53 protein and MIB-1 score. MVD was 10.4+/-4.1(16) in the normal mucosa, 21.5+/-7.9(39) in the adenomas, 35.3+/-9.7(26) in carcinomas (normal versus adenomas, p<0.01; adenomas versus carcinomas, p<0.01). MVD was 25.8+/-5.4(2) in carcinomas confined to mucosa, and 36.1+/-9.6(24) in carcinomas with transmural invasion. The higher MIB-1 score was in carcinomas the more MVD increased but there was no statistical significance (r=0.38, p=0.055). MVD of carcinomas was not associated with nodal metastasis, p53 expression, and DNA ploidy. p53 protein and MIB-1 expression are useful methods for the evaluation of malignancy, and tumor angiogenesis is an early event in a colorectal tumor but MVD does not correlate with prognostic parameters except for the tumor depth.

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.

Expressions of p53 and MIB-1 in Glandular Lesions of the Uterine Cervix.: Seo Young Park, Mee Young Sol, Hye Kyoung Yoon; Korean J Pathol. 1999;33(8):589-595.

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Abstract PDF: The glandular lesions of the uterine cervix can be classified into endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and adenocarcinoma, but the diagnostic criteria and the continuity of endocervical glandular lesions are still controversial. The aim of this study was to evaluate the significance of immunohistochemical findings of p53 and MIB-1 in the discrimination and the continuity of EGD, AIS and adenocarcinoma. The materials for the study included 11 cases of adenocarcinoma, 7 cases of AIS, 12 cases of high grade EGD, and 19 cases of low grade EGD. Also included were eleven benign glandular lesions (5 cases of tuboendometrial metaplasia, 3 cases of mesonephric remnant, 3 cases of microglandular hyperplasia). A strong reaction of more than 5% of the glandular epithelial nuclei was interpreted as positive for p53 protein. MIB-1 expression was analyzed semiquantitatively as negative, 1 , 2 , 3 , depending on the percentage of positive nuclei (less than 1%, 1~9%, 10~39%, > or = 40%, respectively). p53 protein expression was found in 3 (27.3%) out of 11 cases of adenocarcinoma, and 2 (28.6%) out of 7 cases of AIS. But all of high and low grade EGD cases were negative. High MIB-1 labelling index (> or =10%) was found in all adenocarcinoma cases and in 3 (42.9%) out of 7 cases of AIS. But only 2 (17.7%) out of 12 cases of high grade EGD showed high MIB-1 labelling index, and all of low grade EGD and benign lesions showed negligible MIB-1 positivities. In summary, MIB-1 labelling index might be valuable in the discrimination of malignant glandular lesions and endocervical glandular dysplasia from benign lesions, but p53 expression could be a useful parameter in the discrimination of malignant glandular lesions from endocervical glandular dysplasia and benign lesions.

Expression of MIB-1 in Endometrial Adenocarcinoma: Correlation with p53 Protein Expression and Histologic Prognostic Factors.: Mi Jin Kim, Young Ran Shim, Dong Sug Kim; Korean J Pathol. 1999;33(12):1146-1151.

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Abstract PDF: The evaluation of the proliferative potential of malignant neoplasm is of major interest for predicting their biological behavior. MIB-1, a monoclonal antibody against the Ki-67 antigen, is a marker of cell proliferation, which is widely applied to human cancers recently. To assess the growth potential of uterine endometrial carcinoma, we performed immunohistochemical staining of MIB-1 in 34 cases of endometrial adenocarcinoma (endometroid type) from the paraffin sections. We evaluated its correlation with p53 overexpression and known prognostic factors including FIGO grade, nuclear grade, myometrial invasion, and estrogen and progesterone receptors. As a result, the MIB-1 labelling index was significantly correlated with FIGO grade, nuclear grade and myometrial invasion (p<0.05) and there was no significant correlation between MIB-1, ER or PR status. The expression of p53 protein showed significant correlation with FIGO grade and nuclear grade (p<0.05) and there was no significant correlation among p53 protein, myometrial invasion, ER and PR status. The MIB-1 labelling index revealed striking difference between p53 positive and p53 negative group (p<0.05). We concluded that MIB-1 labelling index is associated with poor prognostic parameter in endometrial adenocarcinoma, and may be a useful marker for predicting tumor of high grade and deep myometrial invasion, if MIB-1 labelling index is more than 50% and is accompanied by p53 overexpression.

Correlation between bcl-2 and Caspase-3 Expression and Proliferating Activity in Squamous Neoplasia of the Uterine Cervix.: Kyung Sun Park, Mi Seon Kang, Hye Kyoung Yoon; Korean J Pathol. 2000;34(11):919-926.

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Abstract PDF: Detailed mechanism of uterine cervical cancer progression still remains unclear. Altered programmed cell death (apoptosis) and cellular proliferation are associated with the development of neoplasia. The authors investigated the expressions of bcl-2, which inhibit apoptosis, and caspase-3, which is involved in the induction of apoptosis and has been considered to be correlated with apoptosis, and proliferating activity according to the degree of malignancy in the squamous neoplasia of the uterine cervix. Correlation between bcl-2 and caspase-3 expression and proliferating activity was done. The materials were low grade squamous intraepithelial lesions (LSIL, n=15), high-grade squamous intraepithelial lesions (HSIL, n=15), microinvasive squamous cell carcinoma (n=15), and squamous cell carcinoma (n=15). Immunohistochemical stainings for bcl-2, caspase-3, and MIB-1 were done. bcl-2 and MIB-1 expressions were progressively increased in accordance with the increasing degree of malignancy, but caspase-3 immunoreactivity was higher in LSIL than invasive cancers. There was an inverse relationship between bcl-2 and caspase-3 expression, but the difference did not reach statistical significance. No significant correlation between MIB-1, bcl-2, and caspase-3 expressions was observed. These results suggest that an inhibition of apoptosis and the augmentation of proliferating activity of tumor cells might be separately involved in the development of the cervical squamous neoplasia.

Telomerase Activity and Expression of MIB-1 and bcl-2 in Human Chorionic Villi from Early and Term Normal Pregnancy.: Jung Sook Cho, Young Soon Kang, In Gul Moon, Bum Chae Choi, Jong Pyo Lee, Hoon Taek Lee, Sung Ran Hong; Korean J Pathol. 2000;34(11):927-933.

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Abstract PDF: Telomerase is an enzyme that maintains telomeres and prevents telomere shortening, and may be linked with cellular proliferation or the aging process. The purpose was to examine telomerase activity in human chorionic villi from early and term normal pregnancies, and to analyze the correlation of telomerase activity (TA) with MIB-1 & bcl-2. A total of 37 placentae were obtained from 16 early and 21 term pregnancies. TA was assayed by telomeric repeat amplification protocol, and immunohistochemical staining was performed for MIB-1 & bcl-2 expression. TA & MIB-1 expression were strong in early placenta, but bcl-2 was highly expressed in term placentae. Thirteen (81.25%) of 16 early placentae showed TA, but only 2 (9.52%) of 21 term placentae expressed TA (p<0.01). MIB-1 was observed in nuclei of cytotrophoblast, and the expression rate was 16.09% in early placentae and 2.87% in term placentae (p<0.01). bcl-2 was observed only in the cytoplasm of syncytiotrophoblast. Term placenta demonstrated stronger expression of bcl-2 compared to early placentae (p<0.05). These findings suggest that TA, MIB-1 & bcl-2 expression are critically regulated over the course of gestation: cytotrophoblast, main cells of early chorionic villi, may be a common source of telomerase and proliferative activity. The TA showed good correlation with cellular proliferative activity. Syncytiotrophoblast, may be a main source of bcl-2 expression which is stronger in the term placentae.

Expressions of MIB-1, p53 and CEA in Endocervical Glandular Lesions.: Mi Jin Kim, Young Gi Lee, Dong Sug Kim; Korean J Pathol. 2001;35(1):41-47.

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Abstract PDF: BACKGROUND
Endocervical glandular lesions include glandular atypia (GA), endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS), and invasive adenocarcinoma (IA). The diagnosis of malignant glandular lesions is occasionally difficult to distinguish from benign mimickers, and the morphologic features of EGD remain unsettled.
METHODS
Immunohistochemical stains for MIB-1, p53 and CEA were performed on 81 cases of paraffin-embedded endocervical glandular lesions including 22 IA, 15 AIS, 15 EGD, 13 GA, 8 microglandular hyperplasia (MGH) and 8 tubal metaplasia (TM).
RESULTS
The MIB-1 labelling index of IA was 59.68%, 69.53% for AIS, 26.60% for EGD, 16.03% for benign. p53 overexpression was noted in 4 (18%) cases of IA, 3 (20%) of AIS, but none of EGD and benign lesions. It was Interesting to note that one case of MGH showed p53 staining in low intensity. Diffuse strong cytoplasmic CEA positivity was present in all of IA and AIS, whereas seven (47%) of 15 EGD and 12 (41%) of 29 benign lesions showed focal cytoplasmic CEA positivity. There were significant differences in MIB-1 and CEA immunostainings among the adenocarcinoma, EGD, and benign glandular lesions. Adenocarcinoma was closely related to p53 overexpression, although occurring in a low percentage of the cases.
CONCLUSION
MIB-1 immunostaining can be useful in differentiating among endocervical adenocarcinoma, endocervical glandular dysplasia and benign glandular lesions. p53 overexpression might be helpful in the diagnosis of adenocarcinoma.

Telomerase activity and Expression of MIB-1, Fas and Fas Ligand in Placentas from Women with and without Intrauterine Growth Retardation.: Yi Kyeong Chun, Sung Ran Hong, Moon Ho Yang; Korean J Pathol. 2005;39(1):34-40.

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Abstract PDF: BACKGROUND
The placenta from a pregnancy that is complicated by intrauterine growth retardation (IUGR) tends to be smaller than that from a normal pregnancy. To investigate this difference, we analyzed the telomerase activity, the proliferative activity and the mRNA levels of apoptosis mediators in placentas.
METHODS
In 20 placentas from normal third-trimester pregnancies and 22 placentas form pregnancies that were complicated by IUGR, the telomerase activity was detected by a telomeric repeat amplification protocol assay. The proliferative activity was assessed by immunohistochemical staining using the MIB-1 monoclonal antibody. The expression of the apoptosis mediator was evaluated by semi-quantitative reverse transcription-polymerase chain reactions for fas and fas ligand.
RESULTS
Telomerase activity was detected in 2 (10%) of 20 normal placentas, whereas it was not observed in all tested 13 placentas that were associated with IUGR. The proliferative activity was significantly low in the placentas that were associated with IUGR (7.44+/-2.96%), compared with the normal placentas (11.0+/-3.48%, p=0.002). There was no statistically significant difference in the mRNA levels of fas or fas ligand between two groups.
CONCLUSIONS
Low telomerase and proliferative activities in the placenta may play a role in the pathogenesis of IUGR.

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