Journal of Pathology and Translational Medicine

Original Articles

Relationship between Proliferative Activity and Expression of HBcAg and p53 Protein in Hepatocellular Carcinoma and Surrounding Nontumorous Liver.: So Ya Paik, Ho Guen Kim, Chan Il Park; Korean J Pathol. 1997;31(8):773-781.

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Abstract PDF: In an attempt to discover the factors contributing to the increased proliferative activity in hepatocytes and subsequent development of HCC, the proliferative activity of hepatocytes was compared with the size of regenerative nodules and HBcAg expression status in the surrounding nontumorous liver of 45 surgically resected hepatocellular carcinomas, including 34 HBV related ones. In the tumor, the difference in proliferative activity and the histological grade was analyzed in terms of p53 gene alteration. The proliferative activity was assessed by immunohistochemical methods using Ki-67 monoclonal antibody. HBcAg expression in the surrounding nontumorous liver correlated with both the inflammatory and proliferative activity of hepatocytes (p<0.05). p53 overexpression was associated with high proliferative activity and aggressive phenotype of tumor. No correlation was observed between the proliferative activity of hepatocytes and the size of regenerative nodules in cirrhosis (p>0.05). p53 overexpression was not evident in surrounding nontumorous liver including cirrhosis. In conclusion, the above results are in line with the view that hepatic carcinogenesis is a mutistep, progressive process. In the initial stage, chronic cellular injury incurred by immumologic reaction against HBcAg seems to play a pivotal role in increased cellular regeneration. However, once transformation of hepatocytes occur the major contributor to tumor growth seems to be alteration in p53 tumor suppresor gene.

The Diagnostic Significance of AgNORs and MIB-1 Labelling Index in Atypical Meningioma.: Dae Hong Suh, Dong Sug Kim, Oh Lyong Kim; Korean J Pathol. 1998;32(11):1008-1014.

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Abstract: There is no definite histological criteria which can predict the biologic behavior of meningiomas, although resectability is the most important factor in terms of recurrence. For grading meningiomas, various factors have been studied, such as hypercellularity, nuclear pleomorphism, small cells with high N/C ratio, prominent nucleoli (PN), frequent mitosis, loss of architecture, focal necrosis (FN). We investigated 116 meningiomas to evaluate the correlation between the factors and the proliferative activity using AgNORs and MIB-1 labelling index (LI). They were divided into 3 groups: Group A includes meningiomas with none of the factors; group B with one of the factors; group C with two or more factors. MIB-1 LI was correlated with each factor, but AgNORs was not. There was a statistical difference among group A (<1.28%), B (2.7%) and C (5.1%) (p<0.05) using MIB-1 LI. FN was the most frequently associated with other factors, and it had the highest MIB-1 LI (6.31%). MIB-1 LI of group B was 5.1 2.3%. In group B, the most frequent combination was FN and PN, and it showed the highest MIB-1 LI (5.74%). This study indicates that FN and PN are important for diagnosis of atypical meningioma, and MIB-1 LI appears to be a useful method for estimating the proliferative activity of meningiomas, and 5% or more of MIB-1 LI could help in making a diagnosis of atypical meningioma.

Assay of Proliferative Activity, Clonality and Immortality of.: Hyung Seok Kim, Young Jik Lee, Mee Sook Kim, Hyang Mi Ko, Sang Woo Juhng; Korean J Pathol. 1999;33(9):652-661.

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Abstract PDF: Among the precancerous lesions, dysplasia of the uterine cervix and adenoma of the colon have been widely studied in terms of genetic alterations. However, little has been performed regarding phenotypic alterations of the precancerous lesions. We investigated the relationship among cellular proliferation, clonality, immortality and histopathologic grading of the squamous epithelial lesions of the uterine cervix. Proliferation index (PI) was calculated based on the ratio of the epithelial cells positive for proliferating cell nuclear antigen to the total epithelial cells. Clonality was assayed by X-linked HUMARA polymorphism. For immortality assay, PCR-based TRAP (telomeric repeat amplification protocol) was done and telomerase processivity was calculated by comparison with the positive control. PI increased gradually as the lesions advanced from dysplasia to invasive carcinoma. Among informative case, all of the carcinoma in situ showed monoclonal pattern (7 of 7). Among invasive squamous cell carcinoma, 6 cases showed monoclonal pattern and 2 cases polyclonal pattern. TRAP reaction was positive in 92.6% (25 of 27) of dysplasia (high grade: 14 of 15; low grade: 11 of 12), 95.0% (19 of 20) of carcinoma in situ, 100% (9 of 9) of microinvasive carcinoma, and 92.9% (13 of 14) of invasive carcinoma. It was also positive in 12 of 12 samples of chronic cervicitis or squamous metaplasia near the lesions of dysplasia. There was no difference in TRAP positivity among the dysplasia, carcinoma in situ and invasive carcinoma, whereas telomerase processivity showed significant correlation. These results suggest that proliferative activity and telomerase processivity may be progressive events in oncogenesis, although telomerase activation may be an early event.

Argyrophilic Nucleolar Organizer Region and Expression of Ki-67 in Malignant Lymphoma.: Hee Jung Lee, An Hi Lee, Kyo Young Lee, Chang Suk Kang, Sang In Shim, Byung Kee Kim; Korean J Pathol. 2000;34(4):257-263.

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Abstract PDF: Nucleolar organizer regions (NORs) are loops of DNA which occur in the nucleoli of cells which possess ribosomal RNA genes. The numbers and areas of NORs have been thought to be related to cellular activities. We aimed to investigate the direct relationship between the parameters of AgNORs and cellular proliferative activity using immunohistochemical method with the monoclonal antibody Ki-67, which demonstrates proliferating nuclei. The sequential technique for the simultaneous Ki-67 immunostaining and NOR staining was applied to the same slides of a series of non-Hodgkin's lymphomas (NHL) of the low, intermediate, and high grade type. The number of AgNOR per cell was counted and mean NOR percentage nuclear area (NPNA) was measured by morphometry in both the Ki-67 positive and Ki-67 negative nuclei. The increased immunoreactivity for Ki-67 was found in the high grade than in the low grade non-Hodgkin's lymphoma. This was reflected in the two areas of the palatine tonsils and lymph nodes, the positive cell counts being higher in the follicle center nuclei than in those in the interfollicular compartment. In general the numbers and NPNA of AgNORs were higher in the Ki-67 positive nuclei than in those lacking the antigen in malignant lymphomas as well as in control. The AgNORs numbers and NPNA in controls were the highest in the Ki-67 positive cells in the follicular area and the lowest in the Ki-67 negative cells in the perifollicular area. In malignant lymphomas the numbers and NPNA of AgNORs tended to increase in proportion to their grade in both the Ki-67 positive and negative cells. The numbers of AgNORs of the high grade and the NPNA of the intermediate and the high grade were significantly higher in Ki-67 positive cells than in Ki-67 negative ones. With this double staining method it was now possible to confirm that numbers and NPNA of AgNORs were directly related to the cellular proliferative activity. In maligant lymphoma, among the several parameters of the AgNORs, NPNA in Ki-67 positive cells is proposed to be the most useful marker in determining the prognosis of the patient.

Immunohistochemical Study on the Proliferative Activity of Human Thyroid Tumors.: Myoung Jae Kang, Young Jin Jeong, Woo Sung Moon, Myoung Ja Jeong, Joo Heon Kim, Dong Geun Lee, Ho Yeul Choi, Sang Ho Kim; Korean J Pathol. 1995;29(1):77-84.

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Abstract PDF: For the estimation of the proliferative activity, related to the biologic behaviour, malignant potential, and prognosis, of human thyroid tumors, PCNA(proliferating cell nuclear antigen) immunohistochemical staining was performed on paraffin-embedded sections of 9 normal thyroid tissues, 9 adenomatous goiters, 9 follicular adenomas, 4 Hurthle cell tumors, 12 papillary carcinomas, 4 follicular carcinomas, and 3 anaplastic carcinomas. The results were as follows: 1) The PCNA labeling indices in adenomatous goiter, follicular adenoma, and Hurthle cell tumor were 1.1, 1.5, and 2.4, respectively. They were significantly higher than the labeling index in normal thyroid. 2) The PCNA labeling indices in papillary carcinoma and follicular carcinoma were 3.5 and 4.4, respectively. They were significantly higher than the labeling indices in adenomatous goiter and follicular adenoma, but there was no significant difference between papillary and follicular carcinoma. 3) The PCNA labeling index in anaplastic carcinoma, 14.1, was significantly higher than those in benign and other malignant tumors. According to the results, the PCNA labeling index was well correlated with the malignant potential of a tumor. So the PCNA immunohistochemical staining is thought to be a useful method for the evaluation of the malignant potential and prognosis of a tumor.

The Effect of Preoperative Treatment on Cell Kinetics and Patients Survival in Hepatocellular Carcinoma.: Yoon Jung Choi, Ho Guen Kim, Chan Il Park, Woo Hee Jung; Korean J Pathol. 1994;28(6):605-611.

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Abstract PDF: To evaluate the effect of preoperative treatment on proliferative activity and prognosis of the hepatocellular carcinomas(HCCs), fifty-three surgically resected HCCs were studied. Twenty cases were treated preoperatively and thirty-three were not treated before surgery. The proliferation index(PI, % of proliferating cell nuclear antigen positive cells) of the remaining cancer cases(35.41). Although PI was similar among gross types and among histologic grades, tumors of the expanding type and of the histologic grade I revealed distinctly low PI in pretreated cases. Two-year survival rate was not significantly different between pretreated and not-pretreated cases(67.4 vs 52.7). But the differences between gross types(p<0.05) and between histologic grades(p<0.01) were significant. Total necrosis of tumor occurred in five pretreated patients, all of whom were alive during two-year follow-up. Smaller HCCs showed better prognosis(p<0.01). Although PI appeared not correlated well with the two tear survival rate, the pretreated HCCs preoperative modalities induce tumor necrosis, but do not reduce the proliferative activity of tumor cells significantly, and that pretreatment does not affect the long-term prognosis of HCCs except for the accasions of total necrosis of tumor.

Histologic and Clinical Characteristics of Skin Warts According to the Human Papillomavirus Antigen Expression.: Kun Chang Song, Kwang Gil Lee; Korean J Pathol. 1993;27(4):379-386.

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Abstract PDF: Skin wart is an infectious disease of human papillomavirus(HPV). Its clinical and histopathologic characteristics are largely determined by lesion sties, viral type and host immunity. The infected basal cells and keratinocytes of the epidermis are induced to proliferate by the viral genome. It is, however, not well known how htose factors give rise to histopathologic alterations in the infected basal cells and keratinocytes. So, evaluation of correlation between HPV antigen expression in the wart tissues and clinical and histopathologic charateristics was done on 83 cases of skin warts. The age of patients ranged from 2 to 83 years. Thirty six(43.3%) cases were diagnosed before the age of third decade. The sex ratio was nearly same. Verruca vulgaris was most common(46 cases), followed by verruca plana(26 cases) and verruca palmoplantaris(11 cases). HPV antigen expression was observed in 43 out of total 83(51.8%). It was noted in 47.8%(22/46) of verruca vulgaris, in 46.2%(12/26) of verruca plana and in 81.8%(9/11) of verruca palmoplantaris. HPV antigen-positive groups included more younger patient's age and more higher PCNA than those of HPV negative groups. HPV positive groups also tend to have shorter duration of disease and more numerous mitoses than HPV negative groups. HPV antigen-positive groups showed lower inflammation grade than that of HPV negative groups(p<0.05). The higher the inflammaton grade is, the lower the HPV antigen expression rate. In summary, HPV antigen expression in cutaneous wart tissue is significantly correlated with the proliferative activity of the lesion. It is also significantly correlated with the inflammation that is considered to be the result of cell-mediated immune reaction.

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