- Assay of Proliferative Activity, Clonality and Immortality of.
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Hyung Seok Kim, Young Jik Lee, Mee Sook Kim, Hyang Mi Ko, Sang Woo Juhng
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Korean J Pathol. 1999;33(9):652-661.
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- 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.
- Immunohistochemical and Ultrastructural Studies of Gastric Smooth Muscle Tumor.
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Hyang Mi Ko, Kyung Soo Kim, Jae Hyuk Lee, Woo Sik Juhng, Sang Woo Juhng
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Korean J Pathol. 1996;30(3):245-254.
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- To evaluate the differentiation status of smooth muscle in gastric stromal tumors which were negative for S-100 protein, immunohistochemistry using desmin, actin, myosin and vimentin was performed in 14 cases of gastric smooth muscle tumors. Ultrastructural Examination was also performed. For comparison a case of leiomyoma of the esophagus, a case of the sigmoid colon, 10 cases of the uterus were also examined. The results obtained were as follows. All gastric smooth muscle tumors showed vimentin-positivity. Six of 14 gastric smooth muscle tumors, (5 of 8 leiomyoma and 1 of 4 leiomyosarcoma) showed positivity for desmin, actin, and myosin(42.9%). All esophageal, colonic, and uterine leiomyomas showed diffuse positive reaction for desmin, actin, and myosin. Vimentin positivity was also noted in leiomyoma of the colon and uterus. Ultrastructurally, a few cells in the gastric stromal tumors had scattered microfilaments with dense bodies, subplasmalemmal dense plaques, and micropinocytic vesicles. However, most of the tumor cells did not have any of the ultrastructural features of smooth muscle differentiation. Leiomyomas of the esophagus and uterus showed many cytoplasmic microfilaments with dense bodies.
These results suggest that most of the benign and malignant tumor cells of gastric stromal tumors have features of the undifferentiated cells, immunohistochemically as well as ultrastructurally, although a few cells have. It is speculated that most gastric stromal tumors may have lost their smooth muscle differentiation.
- In Situ mRNA Hybridization and an Immunohistochemical Study of EGFR in Uterine Cervix Cancer.
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Hyang Mi Ko, Chang Soo Park, Sang Woo Juhng
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Korean J Pathol. 1995;29(3):343-351.
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- Epidermal growth factor receptor (EGFR) is an intergral membrane protein. Overexpression or mutation of EGFR may play a role in careinogenesis. Recently, many molecular biologic techniques have been used to study expression of oncogenes. One of them, in situ mRNA hybridization, using paraffin embedded blocks, offers a unique means to allow precise localization within histological preparations, and also overcomes problems relating to translation defects and abnormal translation. In order to confirm the usefulness of epidermal growth factor receptor as a tumor marker, and to compare the expression of EGFR between in situ MRNA hybridization and an immunohistochemical study, in situ MRNA hybridization was performed along with an immunohistochemical study for EGFR in paraffin sections of 84 uterine cervix carcinomas. A positive reaction for EGFR was observed mairdy in the cytoplasm of tumor cells. The vascular muscle layer and uterine muscle tissue around the cancer nest revealed a positive reaction in immunohistochemical stain for EGFR, with a negative reaction for EGFR mRNA. In the cancer nests, the immunohistochemical positive reaction for EGFR was strong in differentiated cells and keratin pearls, but a strong positive reaction for EGFR mRNA was localized in undifferentiated cells. The overall positive of immunostaing for EGFR was 77% for uterine cervix carcinoma; 71 % for carcinoma in situ, 71 % for microinvaseve carcinoma, and 89% for invasive carcinoma.
The overall positivity of EGFR from in situ MRNA hybridization was 94% of the uterine cervix carcinoma; 93% for carcinoma in situ, 93% for microinvasive carcinoma, and 96% for invasive carcinoma. From these results, EGFR is a useful tumor marker for uterine cervix carcinoma, and in situ mRNA hybridization has greater sensitivity and specificity than immunohistochemistry.
- Immunohistochemical Evaluation of HMB-45 and S-100 Protein in Melanocytic Tumors.
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Chang Soo Park, Hwan Kim, Hyang Mi Ko, Kyung Soo Kim, Ji Shin Lee
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Korean J Pathol. 1995;29(2):189-196.
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- Immunohistochemical staining on paraffin sections for S-100 protein improved diagnostic accuracy for melanocytic tumor.
But specificity of S-100 protein in the diagnosis of melanocytic tumor is very low, because S-100 protein was also expressed in neurogenic tumor and salivary gland tumor.
To investigate a specific tumor marker for the malignant melanoma, immunohistochemical staining for HMB-45 and S-100 protein was performed on the paraffin sections of 25 cases of malignant melanoma and 46 cases of nevi. Positive reaction for HMB-45 and S-100 protein was diffusely identified in the cytoplasm of tumor cells. Positive ratio for HMB-45 was 100% in malignant melanoma, 92% in junctional component of compound nevus and 0% in intradermal nevus.
Positive ratio for S-100 protein was 92% in malignant melanoma, 100% in compound nevus and 100% in intradermal nevus. The sensitivity and specificity for HMB-45 in malignant melanoma were 100%, but those for S-100 protein were 92% in sensitivity and 86.7% in specificity. These results indicate that HMB-45 has a high sensitivity and specificity for malignant melanoma cells and it can be quite useful for the histopathological diagnosis of malignant melanoma.
- Cytomegalovirus Infection In a Patient with Hypersensitivity Angiitis due to H-S Purpura: A case report.
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Ji Shin Lee, Hyang Mi Ko, Kyung Soo Kim, Chang Soo Park, J Sang Woo uhng
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Korean J Pathol. 1995;29(1):119-121.
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- Gastrointestinal cytomegalovirus(CMV) infection in adults is observed as a part of a generalized or localized infection in patients who are immunocompromized. We report a case of CMV infection of the small intestine. The patient is a 34 year-old woman who has complained of palpable purpura in the lower extremities and buttocks, and arthralgia of large joints. The skin biopsy showed fibrinoid necrosis and neutrophils with leukocytoclasis, which findings are compatible with hypersensitivity angiitis. The patient received steroid and cyclophosphamide. During the follow-up period, generalized edema and bloody stool were detected.
Resected specimen of small bowel has multiple aphthous ulcer. Microscopically, cytomegalic cells are observed along the endothelial cells and mesenchymal cells. In situ hybridization using DNA probes against CMV revealed positive staining in the cytomegalic inclusions in vascular endothelial and mesenchymal cells.
- The Study of Proliferating Cell Nuclear Antigen (PCNA) Reactivity in Fibrohistiocytic Tumors.
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Jae Hyuk Lee, Yong Han Park, Hyang Mi Ko, Ji Shin Lee, Chang Soo Park
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Korean J Pathol. 1994;28(4):350-357.
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- Fibrohistiocytic tumors are a diverse group of benign and malignant soft tissue lesions, including dermatofibroma, dermatofibrosarcomaprotuberans, and malignant fibrous histiocytoma. On the clinical point of view, the distinction between benign and malignant lesions and malignancy grading is far more important. Therefore, we investigated 23 fibrohistiocytic tumors, using PCNA (PC10) which was a useful marker of proliferating activity, to differentiate the benign lesions from the malignant and correlate with other prognostic factors including tumor necrosis.
cellularity, histologic grade, and mitotic counts. The results obtained were as follows 1) Positive tumor cells were clearly identified by the characteristic diffuse or granular nuclear staining. 2) The number of PCNA-positive tumor cells were 2.16+/-2.39% in dermatofibroma, 16.12+/-7.38% in dermatofibrosacoma protuberans, and 28.02+/-17.47% in the malignant fibrous histiocytoma. The numbers of PCNA-positive tumor cells in the malignant lesions higher than in the benign (p<0.001). 3) Deep seated, large size (>5 cm) and recurred or metastatic cases of MFH were more the high PCNA index (more than 20%) than the low index (less than 20%) groups. 4) PCNA index in MFHs had positive correlation with the number of mitotic counts (r=0.7582, p<0.001), cellularity (r=0.5908, p<0.05) and histologic grade (r=0.4164, p<0.05). These results suggested that reactivity on PCNA might assist in the distinction between benign and malignant lesions in fibrohistiocytic tumors, and could be a useful prognostic factor in the patients with malignant fibrous histiocytoma.
- Fine Needle Aspiration Cytology of Anaplastic Carcinoma with Osteoclastlike Giant Cells of the Thyroid.
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Ji Shin Lee, Hyang Mi Ko, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng
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Korean J Cytopathol. 1994;5(2):172-175.
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- Anaplastic carcinoma of the thyroid is one of the most malignant tumors and survival for longer than three years after diagnosis is exceptional. Multinucleated giant cells of osteoclastlike appearances are seen in some of the anaplastic carcinoma, but only three cases in which the diagnosis was made by fine needle aspiration(FNA) cytology are reported in the international literature. We experienced a case of anaplastic carcinoma with osteoclastlike giant cells in a 66-yr-old female, diagnosed by FNA cytology. The smears revealed two cell populations; multinucleated giant cells and large polygonal or spindle shaped malignant cells.
The FNA cytodiagnosis of anaplastic thyroid carcinoma containing osteoclastilke giant cells was substantiated by subsequent biopsy.
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