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Original Articles
- Flow Cytometric DNA Analysis in Papillary Carcinoma of Thyroid Gland: comparison with Ki-67 immunohistochemical staining.
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Mee Joo, Hye Je Cho
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Korean J Pathol. 1996;30(11):959-965.
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Abstract
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- Nuclear DNA content was measured using a flow cytometric method to analyze 36 paraffin- embedded and 7 fresh tissues of 43 papillary carcinomas of thyroid gland. DNA aneuploidy was found in 3 cases(6.9%) and diploidy in 40 cases(93.1%).
But there were no suggestive findings in clinical history, and cytological and morphological features for aneuploidy.
In 40 diploid cases, S-phase fraction(SPF) were analyzed with regard to sex, age, tumor size, presence or absence of capsular invasion, lymph node involvement and ground glass nuclei. Among the multiple factors, only the tumor size, especially the larger sized-group(above 2cm in tumor diameter) was found to have a statistically significant higher SPF than the smaller sized-group (p<0.05). And high SPF groups relatively well corresponded to the high risk group. Thirty nine cases of papillary carcinoma have also been evaluated for proliferative activity with Ki-67 monoclonal antibody. The average Ki-67 labeling index was 0.36% in total cases, and that of the aneuploid cases was 0.73%, which was higher than that of the diploid cases(0.33%). So. We think that the low aneuploid rate and low Ki-67 labeling index relatively well represent the usual good clinical course of this tumor and the high SPF is a suggestive finding for a high risk group.
- E-Cadherin Expression and DNA Ploidy Analysis in Invasive Squamous Cell Carcinoma of the Uterine Cervix Comparison with those of CIN.
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Yoo Jin Kim, Mee Young Sol, Man Ha Huh, Sun Kyung Lee
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Korean J Pathol. 1997;31(6):557-565.
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Abstract
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- Epithelial cadherin (E-cadherin) is a Ca2+ -dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss is associated with an invasive and poorly differentiated phenotype in a wide range of tumors. Formalin-fixed, paraffin-embedded tissue sections from 36 cases of cervical intraepithelial neoplasia (CIN) and 14 cervical squamous cell carcinomas were investigated for the expression of E-cadherin immunohistochemically.
While E-cadherin expression was usually restricted on the cell membrane of basal and parabasal cells in normal cervix, the presence of cytoplasmic E-cadherin was found to be associated with its grade in CIN lesions. Also, marked cytoplasmic staining was commonly revealed in poorly differentiated ones than well-differentiated squamous cell carcinomas. More intense reactivity of cytoplasmic E-cadherin was frequently seen in the foci of invasion than adjacent carcinoma in situ, and in its periphery than the center of tumor islands. In addition, DNA ploidy and S-phase fraction of squamous cell carcinomas were analyzed and compared with those of CIN lesion. We found that invasive squamous cell carcinomas more frequently disclosed DNA aneuploidy than CIN lesions, and there was correlation between cytoplasmic E-cadherin expression and DNA aneuploidy. Also, cytoplasmic E-cadherin-reactive cervical neoplasms had a higher rate of cell proliferation than that of membranous E-cadherin-reactive cases. These data suggest that the increased cytoplasmic E-cadherin expression may represent one of the abnormalities underlying the loss of polarity and invasiveness of cancer cells, and the abnormal E-cadherin expression combined with/without DNA ploidy or S-phase fraction may serve as a prognostic indicator.
- Flow Cytometric DNA Content Analysis in Breast Cancer Comparison study of fresh and paraffin-embedded tissues.
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Jin Ye Yoo, Hye Jae Cho
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Korean J Pathol. 1998;32(11):993-999.
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Abstract
- DNA content of 25 cases of breast carcinoma was analyzed by flow cytometry in both fresh and formalin-fixed, paraffin-embedded tissue. Aneuploidy in fresh tissue and paraffin-embedded tissues was 72% and 32%, respectively.
There was a 52% agreement in analysis of DNA ploidy between fresh and paraffin-embedded tissues. Most of the discrepancies resulted from loss of aneuploid peaks on the histograms of paraffin-embedded tissue. Mean S-phase fraction was slightly higher in a paraffin-embedded tissue than that in the fresh tissue; 19.2 9.1% versus 16.1 8.8% and there was no significant correlation between the S-phase fractions. In statistical analysis, the histologic and nuclear grades were not correlated with ploidy or mean S-phase fraction. Therefore it is strongly recommended to use the fresh tissue in flow cytometric DNA content analysis of breast cancer.
- AgNOR Counts in S-phase Human Cells.
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Seung Il Kim, Eun Jung Lee
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Korean J Pathol. 1999;33(2):103-107.
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Abstract
- The nucleolus of human cell is a morphologically well recognizable nuclear organelle and the argyrophilic NORs (AgNORs) are nucleic acid-argyrophilic nonhistone protein complex in the nucleoli and the silver staining allows their identification and enumeration at the light microscopic level. The AgNOR counts are in parallel with mitotic activity and vary in different phase of cell cycle. It has been reported that human cells have one AgNOR during interphase and S-phase. However, the correlation between the number of AgNORs and S-phase markers is still controversial and they have never been studied simultaneously. In this study, AgNOR and PCNA were stained simultaneously to find out the relationship of AgNOR counts with cell cycle (S-phase) in human palatine tonsil, gastric carcinoma, liver and brain tissues. S-phase cells (PCNA-positive) were found predominantly in lymphoid follicles in palatine tonsil but gastric carcinoma showed diffuse immunoreactivity for PCNA.
The AgNOR counts varied according to the type and locus of tissue. More than one AgNOR were identified in S-phase cells and some of hepatocytes and neurons in the brain which were not in S-phase contained two or more AgNORs. The above results suggest that the number of AgNOR is a characteristic feature of each type of cells and can be more than one even in S-phase.
- S Phase Kinase Associated Protein 2 Expression in Breast Cancer and Its Prognostic Implications.
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Eun Deok Chang, Eun Jung Lee, Se Jeong Oh, Chang Suk Kang
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Korean J Pathol. 2005;39(2):69-73.
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Abstract
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- BACKGROUND
S Phase Kinase Associated Protein 2 (Skp2), an F-box protein necessary for DNA replication, has recently been demonstrated to be an oncogene. The purpose of this study was to examine the Skp2 expression and to investigate its association with expressions of estrogen receptor (ER), androgen receptor (AR) and HER-2, as well as clinicopathological variables including tumor recurrence.
METHODS
The expressions of Skp2, ER and AR were examined by immunohistochemistry and HER-2 amplification by chromogenic in situ hybridization (CISH) in 117 cases of breast carcinoma.
RESULTS
Skp2 was expressed in 26 patients (22.2%) and was significantly correlated with tumor type (p=0.031), tumor grade (p=0.017) and ER expression (p=0.038). Twenty four (20.5%) of 117 patients had a tumor recurrence, and 6 patients (5.1%) died of multifocal metastases. Tumor recurrence was significantly correlated with histological grade (p=0.041) and lymph node status (p<0.001).
CONCLUSIONS
Although Skp2 expression was statistically insignificant in association with tumor recurrence, it might be useful as a biologic predictor in breast cancer. The simple and reliable immunohistochemical assay presented in this study can be a routine part of breast cancer evaluation and may influence patient management.
- Prognostic Implications of DNA Ploidy and S-phase Fraction Comparing with Other Prognostic Factors in Advanced Coloretal Adenocarcinomas .
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Young Il Yang, Jong Eun Joo
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Korean J Pathol. 1995;29(2):170-180.
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- Dukes' stage of colorectal carcinoma has proven to be the most reliable and conventional prognostic indicator, followed by histological grade, lymph node metastases, tumor size, vascular and neural invasion. Flow cytometric analysis of DNA ploidy and S-phase fraciion (SPF) was examined to elucidate the correlations between sex, age, preoperative serum carcinoembryonic antigen (CEA) value, Dukes' stage, tumor site, size, gross features, histologic grade, and survival rate in 117 paraffin-embedded tissues of 68 cases of colorectal adenocarcinoma in Dukes' stage and 39 cases of colorectal adenoma and 10 cases of normal colonic mucosa.
DNA aneuploidy was detected in 30 cases(44%) in adenocarcinomas and 6 cases (15%) in adenomas. Although the DNA ploidy and SPF did not show any correlation with sex, age, preoperative serum CEA level, Dukes' stage, tumor size, site and gross features, the incidence of DNA aneuploidy in the moderately differentiated adenocarcinomas was significantly higher than that of the well differentiated adenocarcinomas (p=0.0127) An apparent correlation was found between survival rate and DNA ploidy, Dukes' stage, histologic grade and preoperative serum CEA value. Dukes' stage was the most reliable prognostic indicator (p=0.0106), followed by histologic grade (p=0.0230), DNA aneuploidy (p=0.0251) and preoperative serum CEA level. (p=0.0369) In the patients with Dukes' stage C, DNA aneuploidy was more important than histologic grade as a prognostic indicator (p=0.0202). Although high SPF, greater than 21% in adenocarcinoma, was associated with the lower 5-year survival rate (12.0%), it was not statistically significant.
These results suggest that DNA aneuploidy is regarded as biologic aggressiveness and considered as independent and/or dependent prognostic indicator along with Dukes' stage.
However, prognostic utility of the SPF was not significant.
- Correlation of Histologic Findings of Ovarian Epithelial Tumors with Expression of Proliferating Cell Nuclear Antigen and Flow Cytometric DNA Analysis.
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Sang Yeop Yi, Soon Hee Jung, Kwang Gil Lee
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Korean J Pathol. 1995;29(1):68-76.
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- The prognosis of malignant ovarian tumor is poorer than that of borderline malignant ovarian tumor, Therefore an accurate diagnosis and estimation of the biologic behavior of the tumor are necessary for proper management of the patient.
The histologic investigation of the tumor may provide information on the estimation of the malignant potential of tumor cells, but it may be a questionable method because of the subjective determination of tumor grade. Quantification of proliferative activity of tumor cells may play a role as an objective method to provide an estimation of the malignant potential of tumor cells. An evaluation of histologic findings was done on 84 cases of ovarian mucinous and serous tumors that were surgically resected and diagnosed during the period from January 1981 through July 1992. The proliferating cell nuclear antigen (PCN A) labelling index estimated from the immunohistochemical stain for PCN A and the Sphase fraction and porliferative index obtained from flow cytometric DN A analysis were assessed each other with histologic findings. The results are as follows: The presence of aneuploidy in malignant tumors was statistically significant as compared with benign tumors.
The borderline malignant tumors showed no significant difference between the number of diploidy and aneuploidy.
The PCNA labelling index, S-phase fraction and proliferative index tended to increase as the histologic grade of tumors went up. They were higher in malignant tumors than in others. The PCN A labelling index, S-phase fraction and proliferative index were higher in tumors with aneuploidy than in those with diploidy. In contrast to borderline malignant tumors, the PCNA labelling index in malignant tumors revealed a significant relation with the mitotic index. The S-phase fraction and proliferative index showed, in malignant tumors, a close correlation with the architectural grade and nucleolar grade, but not in borderline malignant tumors. Considering these results, the presence of aneuploidy, PCNA label.
- DNA Ploidy and S-Phase Fraction in Proliferative Hepatic Lesions of Rat Liver Induced by Dietylnitrosamine and Partial Hepatectomy.
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Chan Choi, Sung Hee Cho, Hyung Bae Moon, Ki Jung Yun, Hun Taeg Chung, Sang Woo Juhng
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Korean J Pathol. 1991;25(4):346-356.
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- We have investigated the changes of DNA ploidy and S-phase fraction in proliferative lesions of rat liver.
Proliferative lesions were induced by diethylnitrosamine and partial hepatectomy. DNA ploidy was measured by flow cytometer, and S-phase fraction was measured by in situ bromodeoxyuridine(BRdU)-anti BRdU monoclonal antibody techniques. Normal liver and initiated lesion revealed DNA diploidy or DNA tetraploidy. Hepatocyte nodule (NODULE) and hepatocelular carcinoma (HCC) revealed DNA diploidy, tetraploidy or aneuploidy. S-phase fraction was 1.0+/-0.9, 1.0+/-0.9m 3.7+/-2.3, 5.5+/-4.9, and 13.8+/-11.6 in normal liver, initiated lesion, NODULE not associated with HCC, NODULE associated with HCC, and HCC, respectively. In NODULE associated with HCC, it was widely distributed, ranging from 0.8 to 15.5%. In conclusion, S-phase fraction appeared to be increased as the hepatocarcinogenesis proceeded, but DNA ploidy did not. There was a heterogeneity of DNA ploidy and S-phase fraction in the proliferative hepatic lesions.
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