Journal of Pathology and Translational Medicine

Volume 31(1); January 1997

Original Articles

The prognostic significance of tumor angiogenesis, proliferating cell nuclear antigen(PCNA), and the Ki-67 index in carcinoma of the uterine cervix.: Chan Pil Park, Seung Yon Lee, Moon Hyang Park; Korean J Pathol. 1997;31(1):1-14.

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Abstract PDF: Angiogenesis, the induction of new capillaries and venules, is associated with tumor growth. This study was designed to determine whether cervical carcinomas are angiogenic, and to investigate whether tumor angiogenesis can serve as a prognostic factor in cervical carcinoma. Surgical specimens of 47 cervical carcinomas were immunohistochemically stained specifically for endothelial cells with factor VIII-related antigen to identify all vessels. Microvessels were counted from photographs of 200x microscopic fields. In addition, thirty-seven cases were studied by immunohistochemical means using the monoclonal antibodies for PCNA and for Ki-67 to determine tumor cell proliferation rates in cervical carcinomas. The microvessel count(MVC), the PCNA labelling index, and the Ki-67 index were calculated and compared with known prognostic factors and disease free survival rates in cervical carcinomas. A wide range in the MVC count(range 12-100 mean=38.2+/-19.2), the PCNA labeling index(8-69% mean=33.6+/-15.2%), and in the extent of Ki-67 staining(0-43% mean=10.3+/-10.5%) was observed, indicating considerable variation of tumor angiogenic activity and tumor growth rates. This study showed statistically significant correlations in disease free survival rates with both lymph node status and the microvessel count. However, there was no significant difference in disease free survival rates between tumor stage, age, the PCNA labelling index, and the Ki-67 index.

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.

Angiogenensis and Overexpression of p53 Gene Produc in Brain Tumor.: Jeong Yun Shim, Ho Guen Kim, Tai Seung Kim; Korean J Pathol. 1997;31(1):23-33.

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Abstract PDF: Angiogenesis depends on the net balance between positive and negative angiogenic factors. Tumor cells are angiogenic resulting from increased production of positive factors and decreased production of negative factors. Among these, vascular endothelial growth factor and glioma- derived angiogenesis inhibiting factor are related to glioblastoma multiforme. The p53 gene is more frequently mutated than any other known oncogene or tumor suppressor gene in human tumors including glioblastoma multiforme. Angiogenesis is reported to be controlled by p53 regulation in recent studies. To examine the effect of p53 overexpression on angiogenesis in glioblastoma multiforme, we performed immunohistochemical staining in 51 cases of glioblastoma multiforme, using monoclonal antibodies to p53 protein and factor VIII. 20 cases of low grade astrocytoma were used as control. p53 overexpression was present in 15(75%) of 20 cases of low grade astrocytoma and the mean vessel count was 37.7+/-9.9 at x200 field and 17.5+/-5.8 at x400 field. p53 overexpression was present in 35(68%) of 51 cases of glioblastoma multiforme and the mean vessel count was 91.9 45.8 at x200 field and 40.7 19.1 at x400 field. Mean vessel count in low grade astrocytoma with p53 overexpression was 39.4 10.2 at x200 field and 18.9 5.7 at x400 field, while in cases without p53 overexpression it was 32.4+/-7.6 at x200 field and 13.2 3.5 at x400 field. Mean vessel count in glioblastoma multiforme with p53 overexpression was 94.5+/-51.8 at x200 field and 42.1+/-16.8 at x400 field, while in cases without p53 overexpression it was 86.1+/-29.5 at x200 field and 37.1+/-16.8 at x400 field. The mean survival time was 12.4 months in the 39 cases of glioblastoma multiforme in which follow-up studies were possible. Significant prognostic factors were age, p53 overexpression and adjuvant therapy. These results show that p53 gene mutation is one of the many contributing factors to angiogenesis in glioblastoma multiforme. In addition, other oncogenes and tumor suppressor genes, as well as growth factors may be involved. Age, p53 overexpression and adjuvant therapy proved to be significant prognostic factors, while microvessel density was not.

Renal Dysplasia: A Clinicopathologic Review of Six Cases.: Gil Hyun Kang, Jong Ok Kim, Bum Kyung Kim, Kwang Sun Suh; Korean J Pathol. 1997;31(1):34-39.

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Abstract PDF: Renal dysplasia results from aberrant histogenesis in metanephric differentiation. It is characterized morphologically by abnormal organization and a persistence of primitive structures, such as cartilage, undifferentiated mesenchyme, and immature tubules. Six cases of renal dysplasia from five children and one adult are reviewed. Five patients were female and one patient was male. The chief complaint was urinary incontinence in four patients, dysuria in one patient, and the sixth patient suffered from vesicoureteral reflux. No evidence of family history of renal dysplasia in any patient was seen. According to Risdon's classification, three cases were hypoplastic dysplasia, one case was dysplasia in a duplex system, one case was dysplasia in a triplex system, and one case was dysplasia with vesicoureteral reflux. The ipsilateral ectopic ureteral orifice was identified in four patients, two of which drained into a Gartner's duct cyst, and the orifice was suggested in one patient. On histologic examination, all cases showed primitive ducts surrounded by concentrically arranged primitive mesenchyme. Nests of metaplastic cartilage were observed within the stroma in three of the six cases.

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.

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.

Case Reports

Malignant Fibrous Histiocytoma of the Liver.: So Yeong Oh, Myoung Ja Chung, Sang Ho Kim; Korean J Pathol. 1997;31(1):59-62.

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Abstract PDF: Primary sarcomas of the liver are rare. A case of primary malignant fibrous histiocytoma of the liver is reported. A 55-year-old male was admitted with epigastric pain. An abdominal computed tomographic scan disclosed a 10cm, low-density area in the left lobe of the liver. Histological examination of the resected tumor showed bundles of spindle cells arranged in a storiform pattern. In some areas, many bizarre giant cells were scattered. Immunohistochemically, tumor cells were positive for alpha 1-antitrypsin and alpha 1-antichymotrypsin, and weakly positive for vimentin. The tumor cells did not express cytokeratin, desmin or alpha fetoprotein.

Inflammatory Myofibroblastic Tumor in Posterior Mediastinum.: Seung Sam Paik, Seok Hoon Jeon, Se Jin Jang, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1997;31(1):63-67.

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Abstract PDF: Inflammatory myofibroblastic tumor(IMT) or inflammatory pseudotumor is a rare, solid tumor that most often affects children. This tumor is characterized by a spindle cell proliferation admixed with a variety of inflammatory cells. Although it has disputed nosology, a distinctive fibroinflammatory and even pseudosarcomatous appearance have been well appreciated. Herein, we report a case of IMT in the posterior mediastinum in a 19-year-old girl with clinical findings. The immunohistochemical and ultrastructural studies on the tumor cells are reported, and their distinctive characteristics are discussed in details.

Primary Necrotizing Granulomatous Vasculitis of the Stomach.: Myeong Cherl Kook, Sang Yong Song, Yong Il Kim, In Sung Song, Keun Wook Lee; Korean J Pathol. 1997;31(1):68-74.

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Abstract PDF: A 55-year-old woman suffered from upper abdominal pain for two months and remained refractile against the anti-ulcer regimen. The palliative gastrectomy specimen revealed multiple shallow ulcerations on the thickened mucosal folds mainly in the antrum and body along the greater curvature where multiple, whitish nodules were found in the submucosa. Microscopically, individual submucosal nodules clearly corresponded to the necrotizing granulomatous vasculitis which were featured with diffuse fibrinoid necrosis of arterial walls accompanying granuloma formation and heavy infiltration of neutrophils, eosinophils, histiocytes and giant cells. Similar vasculitic lesions involved venules and arterioles. There were scattered vasculitic changes in the liver biopsy specimens and omentum. There were no clinical presentations or serological support of systemic involvement including systemic lupus erythematosus, Henoch-Schoenlein purpura, cryoglobulinemia or Churg-Strauss granulomatous vasculitis. We conclude that this is a hitherto undescribed primary necrotizing granulomatous vasculitis predominantly involving the stomach.

Giant Cell Tumor of the Larynx: Report of a case.: Soya Paik, Yoon Mee Jeen, Woo Ick Yang, In Joon Choi, Young Ho Kim; Korean J Pathol. 1997;31(1):75-78.

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Abstract PDF: Giant cell tumor arising in the osteocartilaginous tissue of the larynx is extremely rare. The few reported cases have all occurred in men older than 20 years and the site of origin has been exclusively localized to the thyroid and cricoid cartilages that are known to undergo enchondral ossification. The formation of giant cell tumor in larynx is thought to be related to this enchondral ossification process. We report a case of giant cell tumor arising in the thyroid cartilage of a 39 year old man. CT scan of the neck revealed a well defined mass of soft tissue density replacing the right thyroid cartilage. Grossly the tumor was well demarcated with a distinctive pushing margin except for the area bordering the submucosa of the larynx where it showed focally an infiltrative pattern of growth. Microscopically multinucleated giant cells were found dispersed regularly among the spindle cells. Although mitoses were frequently noted in the spindle cells there was no atypicality or pleomorphism. Total laryngectomy was performed without further treatment. Postoperative follow up for 6 months has proved the patient to be alive and well without recurrence.

Endotracheal Neurilemmoma.: Hwa Sook Jeong, Jong Myeon Hong, Yoon Woo Noh, Hyung Geun Song; Korean J Pathol. 1997;31(1):79-82.

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Abstract PDF: Neurilemmomas of the trachea are extremely rare. The most common site of them is the distal third of the trachea and the age of the patients at presentation varied from 6 to 78 years old. They usually have a freqeuntly very long natural history, causing symptoms only after they have attained a considerable size. We experienced a case of near-total obstruction of the trachea by an intraluminal sessile neurilemmoma. The patient was a 66-year-old man with 2-year history of progressive exertional dyspnea and had several episodes of pneumonitis associated with productive cough. Grossly, the tumor was a well-circumscribed mass. Microscopically, typical cellular Antoni A and myxoid Antoni B areas were revealed.

Adenomyoepithelioma of the Breast.: Sang Yong Lee, Hea Kyoung Hur, Dae Cheol Kim, Seo Hee Rha, Sook Hee Hong; Korean J Pathol. 1997;31(1):83-86.

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Abstract PDF: Adenomyoepithelioma is a rare benign tumor which occurs mainly in the skin, salivary gland and very rarely in the breast. Histologically this tumor demonstrates biphasic differentiation of luminal epithelial cells and myoepithelial cells. We report a case of adenomyoepithelioma occuring in the outer lower quadrant of the right breast of a 56-year-old female, confirmed histologically with an aid of immunohistochemistry. This is the first documented report in Korean literature.

Original Article

Primary Biliary Cirrhosis-Autoimmune Hepatitis Overlap Syndrome.: Jong Yup Bae, Young Nyun Park, Chanil Park; Korean J Pathol. 1997;31(1):87-90.

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Abstract PDF: Cases sharing features of both primary biliary cirrhosis and autoimmune hepatitis have been reported as a mixed type, overlap syndrome, immunocholangitis and autoimmune cholangiopathy. A primary biliary cirrhosis- autoimmune hepatitis overlap syndrome is unusual and characterized by overlapping features; cholestasis, high titer of alkaline phosphatase, bile duct damage and granulomas in the liver biopsy, high antinuclear antibody, increased IgG and IgM and intra-acinar hepatitis with piecemeal necrosis. Autoimmune mechanisms are thought to play a major role in the pathogenesis of the overlapping syndrome and the bases of immunosuppressive therapy. A 58-year-old female patient shows overlapping clinical and laboratory findings, chronic active hepatitis in initial liver biopsy which transits to primary biliary cirrhosis with cholangitis and granulomas. This is a case of hepatobiliary lesion showing overlapping features of both primary biliary cirrhosis and autoimmune hepatitis over 3-year period.

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