BACKGROUND: In order to investigate the roles of p16 and Rb, their expression was evaluated in 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced ovarian cancers of rats. METHODS: DMBA-coated silk was inserted into both ovaries of 20 9-week-old Sprague-Dawley rats. The experimental period lasted 20 weeks. The tumor histology was classified and the expression of p16 and Rb in the ovarian tumors was analyzed by immunohistochemistry and Western blot. RESULTS: The p16 and Rb labeling index was significantly lower in the ovarian cancers than the normal ovarian surface epithelium of a rat. There were no differences among the cancer types. In Western blot analysis, the expressions of p16 and Rb in ovarian cancers were lower than those in normal ovarian tissue. No correlation was present between p16 and Rb. CONCLUSION: The abnormal expression of p16 and Rb occurs in DMBA-induced rat ovarian cancer and might be involved in carcinogenesis.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Blotting, Western ; Carcinogenesis* ; Epithelium ; Female ; Immunohistochemistry ; Ovarian Neoplasms ; Ovary ; Rats* ; Rats, Sprague-Dawley ; Retinoblastoma Protein ; Silk

BACKGROUND: Uterine cervical cancer is the most prevalent cancer in Korean women, and the incidence of adenocarcinoma has been increasing. Loss of heterozygosity (LOH) analysis is used to identify regions which harbor a putative tumor suppressor gene. METHODS: DNA was extracted from the microdissected normal and malignant lesions of 34 uterine cervical adenocarcinomas, 2 adenosquamous cell carcinomas, 13 squamous cell carcinomas, and 10 endometrial adenocarcinomas. LOH and microsatellite instability (MSI) analysis were performed using microsatellite markers, D3S4103 (3p14.2), D3S1284 (3p12), D3S1289 (3p21.2-21.1), D3S1307 (3p25-ter), THRB (3p22-24.1), and D11S35 (11q22). The expression of Fhit protein was compared with the genetic abnormalities. RESULTS: Microsatellite alterations at 3p were detected in 37% of cervical adenocarcinomas, 16% of squamous cell carcinomas, and 43% of endometrial adenocarcinomas. The alterations of 11q were found in 17% of cervical adenocarcinomas. Microsatellite alterations of D3S1307 and D11S35 were detected in uterine cervical adenocarcinomas with high frequency. The frequency of FHIT protein loss is higher in the cervical squamous cell carcinoma than in cervical and endometrial adenocarcinomas. CONCLUSION: Tumor suppressor gene of uterine cervical adenocarcinoma may be located in 3p25-ter and 11q22.
Adenocarcinoma* ; Carcinoma, Squamous Cell ; Cervix Uteri ; DNA ; Female ; Genes, Tumor Suppressor ; Humans ; Incidence ; Loss of Heterozygosity ; Microsatellite Instability ; Microsatellite Repeats* ; Uterine Cervical Neoplasms

BACKGROUND: This experiment was designed to study the cell kinetics of hepatocellular carcinoma (HCC) in both hepatitis B virus X (HBx) transgenic mice and humans. METHODS: The immunohistochemical stain of proliferating cell nuclear antigen (PCNA) and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay of apoptosis were used on formalin fixed-paraffin embedded tissues. RESULTS: PCNA labeling indices (PCNA-LI) in the liver of HBx transgenic mice were markedly increased in HCC (11.3%) compare to the dysplastic areas (1.3%) and in the liver of non-transgenic littermates (0.1%). There was no significant difference of PCNA-LI in the dysplastic areas between HCC developed mice and non-HCC developed mice. Apoptosis labeling indices (Apoptosis-LI) in both the dysplastic areas and HCC of HBx transgenic mice were similar to those of non-transgenic littermates. PCNA-LI was markedly increased in human HCC (28.9%) compare to the background of HCC (2.9%) and the control liver (2.9%). Apoptosis-LI was decreased in human HCC (0.3%) compare to the background of HCC (0.4%) and the control liver (1.0%). Conclusion : There is a marked increase of cell proliferating activity in human HCC and in HCC of HBx transgenic mice, and there is a decrease of apoptosis in human HCC, but not in HCC of HBx transgenic mice.
Animals ; Apoptosis* ; Carcinoma, Hepatocellular* ; Formaldehyde ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans* ; Kinetics ; Liver ; Mice ; Mice, Transgenic* ; Proliferating Cell Nuclear Antigen*

BACKGROUND: Hepatocellular cholestasis denotes the alteration of bile secretion by hepatocytes. The causes, degree of hepatocyte injury and concomitant bile duct loss are considered to influence the clinical course. METHODS: The causes and pathological features of hepatocellular cholestasis were analyzed in 62 cases of liver biopsies; and the causes of primary biliary cirrhosis, primary sclerosing cholangitis, and biliary obstruction were not included. RESULTS: The mean age of the patients was 42.2 years, and the ratio of male to female was 1.8:1. Fifty-eight cases (94%) showed cholestatic hepatitis, and 4 cases (6%) showed pure cholestasis without hepatitis activity. The majority of the cases (52 cases, 84%), including 19 cases of herbal medicine, was related to drugs. Loss of bile duct was found in 12 cases (19%), which were all cases of chronic cholestasis. All of them had drug histories, including 9 cases of herbal medicine. Clinical follow-up was performed in 9 out of the 12 cases with bile duct loss, and all of them showed elevated total bilirubin and/or alkaline phosphatase levels for more than 6 months. CONCLUSION: Drugs are the major cause of hepatocellular cholestatic hepatitis/cholestasis; and information about drugs, including herbal medicines, should be considered for proper evaluation of liver biopsy with hepatocellular cholestasis. Bile duct loss should be evaluated in the cases of chronic hepatocellular cholestasis, especially in drug induced cases.
Alkaline Phosphatase ; Bile ; Bile Ducts ; Bilirubin ; Biopsy* ; Cholangitis, Sclerosing ; Cholestasis* ; Female ; Follow-Up Studies ; Hepatitis ; Hepatocytes ; Herbal Medicine ; Humans ; Liver Cirrhosis, Biliary ; Liver* ; Male

BACKGROUND: Resistance to the potent growth inhibitory effects of TGF- (transforming growth factor-) is a characteristic of many malignancies. TGF- insensitivity has been attributed to alterations in the number and function of the TGF- receptors as well as disturbances of downstream signal transduction. The aim of this study was to examine the expression of TGF-1 and its receptors in human colorectal cancer tissue and determine its relationship with cancer growth and with prognostic factors. METHODS: Immunohistochemical staining of TGF-1, TGF-RI, and TGF-RII was performed on 20 human colorectal adenomas, 30 carcinomas and 10 normal mucosas as a control. RESULTS: The staining indices of TGF-1, TGF-RI, and TGF-RII increased in adenomas and carcinomas compared with normal mucosas and adenomas, respectively. In adenomas the staining index of TGF-1 significantly increased with the severity of atypism. The staining index of TGF-RII increased in the carcinomas in the right colon and rectum, compared with those in the left colon. CONCLUSION: The enhanced expression of TGF-1, TGF-RI and II in the colorectal carcinoma suggests an important role of colorectal carcinogenesis and tumor progression.
Adenoma ; Carcinogenesis ; Colon ; Colorectal Neoplasms* ; Humans* ; Immunohistochemistry ; Mucous Membrane ; Rectum ; Signal Transduction ; Transforming Growth Factor beta

BACKGROUND: Microsatellite instability (MSI), which is caused by a deficient mismatch repair system, is seen in most of the hereditary non-polyposis colon cancers and a portion of sporadic colorectal cancers. METHODS: Two hundreds forty-six consecutive sporadic colorectal cancer patients were analyzed for MSI using an ABI 377 automatic sequencer and fluorescent dye-labelled primers (BAT-25 and BAT-26). RESULTS: The overall incidence of MSI in studied cases was 9.8% (24/246). This incidence is lower than most of the reported incidences in western countries. The incidence of MSI tumors in the proximal colon was 29.6%, while that of the distal colon was only 4.2% (p<0.001). MSI in sporadic colorectal cancers was more prevalent in poorly differentiated adenocarcinoma. In contrast to western countries, mucinous carcinoma did not show higher incidence of MSI. CONCLUSION: The results suggest that MSI frequently occurs in cancers of the proximal colon and in tumors with poorly differentiated histology.
Adenocarcinoma ; Adenocarcinoma, Mucinous ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; DNA Mismatch Repair ; Humans ; Incidence ; Microsatellite Instability* ; Microsatellite Repeats* ; Sequence Analysis

BACKGROUND: A practical RNA in situ hybridization method using digoxigenin labeled RNA probes is described in order to evaluate the technical difficulties and problems in RNA in situ hybridization. METHODS: The paraffin sections, routinely processed in the Pathology Laboratory, were tested for the possibility of RNA in situ hybridization instead of the RNase free paraffin sections, fixed in 4% paraformaldehyde and prepared using RNase protection procedures. RESULTS: Most of the paraffin sections, fixed in 10% neutral formalin solution in fresh condition, showed relatively good reaction of RNA in situ hybridization, although the necrotic tissue and autopsy specimens showed poor reaction of RNA in situ hybridization. A refixation procedure using a 4% paraformaldehyde solution was evaluated for optimal expression of mRNA in the paraffin sections. CONCLUSION: The treatment of 4% paraformaldehyde before the treatment of proteinase K showed better in situ hybridization than did the treatment of 4% paraformaldehyde after the treatment of proteinase K. Also a new Polymerase Chain Reaction (PCR)-based method of RNA probe production showed consistently good results.
Autopsy ; Digoxigenin* ; Endopeptidase K ; Formaldehyde ; In Situ Hybridization* ; Paraffin ; Pathology ; Polymerase Chain Reaction ; Ribonucleases ; RNA Probes ; RNA* ; RNA, Messenger

BACKGROUND: Malignant cell nuclei, in general, have increased amounts of heterochromatin and decreased electron densities of euchromatin, making the chromatin pattern coarser than that of benign cell nuclei. The chromatin pattern in benign and malignant cells, however, is barely explained in terms of molecular structure. In this study, the chromatin pattern of metaplastic and carcinomatous squamous cells of the uterine cervix was correlated with transcriptional activity by ultrastructural autoradiography. METHODS: Punch-biopsied tissues were cultured with 3H-uridine for 5 minutes and processed for electron microscopy. Thin sections of the tissues on nickel grids were covered with photosensitive emulsion and kept cold in a dark room for 10 to 16 weeks. After development and staining, the tissues were observed by electron microscopy. RESULTS: The nuclei of the metaplastic squamous cells consisted mostly of euchromatin. A few silver grains were observed, mainly at the periphery of the nuclei. The nuclei of the carcinomatous cells had increased amounts of heterochromatin along the nuclear membrane, and also in the euchromatin area. Silver grains were observed mainly at the boundary between the heterochromatin and euchromatin. CONCLUSION: These findings suggest that an increased amount of heterochromatin in carcinomatous cells results in an increase of the boundary area between the heterochromatin and euchromatin, an area which may be a transcriptionally active site.
Autoradiography ; Catalytic Domain ; Cell Nucleus ; Edible Grain ; Cervix Uteri ; Chromatin ; Euchromatin* ; Female ; Heterochromatin* ; Microscopy, Electron ; Molecular Structure ; Nickel ; Nuclear Envelope ; RNA, Messenger* ; Silver

Smooth muscle cell metaplasia is an extremely rare form of stromal differentiation in fibroadenomas. We describe a case of fibroadenoma with exuberant smooth muscle cells in a 72-year-old woman. The mass was located in the upper central portion of the left breast. It was well circumscribed and its greatest dimension was 3 cm. Histologically, the glandular elements resembled the appearance of fibroadenoma, but the stromal elements were composed of spindle cell bundles with abundant eosinophilic cytoplasm and elongated cigar-shaped nuclei. Neither mitotic activity nor cellular atypia was seen. The stromal cells were immunohistochemically positive for smooth muscle actin, calponin, desmin, and estrogen receptor-beta, but negative for CD34, S-100 protein, p63, CD10, estrogen receptor-alpha, progesterone receptor and cytokeratin. These results proved that the stromal cells showed features of smooth muscle cells.
Actins ; Aged ; Breast ; Calcium-Binding Proteins ; Cytoplasm ; Desmin ; Eosinophils ; Estrogens ; Female ; Fibroadenoma ; Humans ; Keratins ; Metaplasia ; Microfilament Proteins ; Muscle Cells ; Muscle, Smooth ; Myocytes, Smooth Muscle ; Receptors, Progesterone ; S100 Proteins ; Stromal Cells

Myofibrillar myopathies (MFMs) are a genetically or clinically heterogeneous group of diseases that are characterized by focal myofibrillar dissolution associated with accumulation of myofibrillar degradation products and ectopic expression of multiple proteins. Since MFMs show morphologically distinct features but consist of genetically and clinically heterogeneous diseases, muscle biopsy is important for the diagnosis. A 20-year-old man complained of progressive weakness and atrophy of both legs for two years. He had a dysmorphic face and short stature. The light microscopic examination of his muscle biopsy showed mixed myopathic and neurogenic changes. Many myofibers with multiple clusters of blue red rod-like structures and cytoplasmic inclusions were noted. Immunohistochemistry showed a focal positive reaction in sarcoplasm to desmin and myotilin antibodies. An electron microscope study revealed variable abnormalities of myofibrillar structures. To the best of our knowledge, this is the first reported case of MFM with pathology findings in Korea.
Antibodies ; Atrophy ; Biopsy ; Desmin ; Electrons ; Humans ; Immunohistochemistry ; Inclusion Bodies ; Korea ; Leg ; Light ; Muscles ; Muscular Diseases ; Proteins ; Young Adult