Many epidemiologic and clinical studies have indicated that the frequency of breast cancer was lower in parous women than in nulliparous women. Moreover, the incidence of breast cancer has been reported to be lower in women with early childbirth than in women with late childbirth. To verify the effect of childbirth and the age at first childbirth on carcinogenesis and progression of breast cancer, we induced breast cancer by 7,12-dimethylbenanthracene (DMBA) in 120 female Sprague-Dawley (SD) rats, and divided them into control or experimental (DMBA-treated) nulliparous, early childbirth, and late childbirth groups to observe the incidence, latency, and size of breast cancer. Argyrophilic nucleolar organizer regions (AgNOR) count and the expression of C-erbB-2, proliferating cell nuclear antigen (PCNA), Ki-67, and minichromosome maintenance protein 2 (MCM2) in breast cancer tissues were detected by immunohistochemistry. The breast cancer incidences were 95.0%, 16.7%, and 58.8% in the experimental nulliparous, early childbirth, and late childbirth groups, respectively (all P < 0.05). Between any two of these groups, the latency was significantly different, but tumor size was similar. AgNOR count and the expression of C-erbB-2, PCNA, Ki-67, and MCM2 were significantly higher in the experimental nulliparous group than in the experimental early or late childbirth groups (P < 0.05), but no significant differences were observed between the latter two groups. Taken together, the results suggest that childbirth, especially early childbirth, can reduce the incidence and postpone the onset of DMBA-induced breast cancer.
9,10-Dimethyl-1,2-benzanthracene ; Animals ; Antigens, Nuclear ; metabolism ; Carcinogens ; Cell Transformation, Neoplastic ; Female ; Ki-67 Antigen ; metabolism ; Mammary Neoplasms, Experimental ; chemically induced ; metabolism ; pathology ; physiopathology ; Minichromosome Maintenance Complex Component 2 ; Nuclear Proteins ; metabolism ; Parity ; Pregnancy ; Proliferating Cell Nuclear Antigen ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, ErbB-2 ; metabolism ; Tumor Burden

The proliferative activity of gastric adenomas from 18 patients (42 endoscopic procedures) was compared with follow-up results. These cases were gastric adenomas proven by follow-up with repeated endoscopic procedures for more than 2 years, or were confirmed as gastric adenocarcinoma thereafter by histopathologic examination. Among the eighteen cases, nine showed carcinoma in the subsequent biopsies (group 1) and the remaining nine did not result in carcinoma (group 2). The proliferating cell nuclear antigen (PCNA) positivity rates of the two groups were significantly different (P < 0.01). The average PCNA positivity in group 1 was 33.1%, while it was 10.0% in group 2. The risk of developing carcinoma increased as the PCNA positivity increased: 0% in the low PCNA positivity group, 41% in the mid-positivity group and 89% in the high positivity group. We concluded that growth fraction could be taken into account as one of the most important prognostic factors for gastric adenoma, and accordingly repeated endoscopic biopsies with close follow-up should be carried out especially in the high PCNA positivity group.
Adenoma/*immunology ; Antigens, Neoplasm/immunology/*metabolism ; Carcinoembryonic Antigen/metabolism ; Cell Cycle ; Follow-Up Studies ; Gastroscopy ; Humans ; Nuclear Proteins/*metabolism ; Prognosis ; Proliferating Cell Nuclear Antigen ; Stomach Neoplasms/*immunology

OBJECTIVE: In this study, we investigated the relationship between the histologic grading of meningiomas and proliferative potentials determined by the Ki-67, proliferating cell nuclear antigen(PCNA) and flow cytometry (FCM) with the aim of determining whether these potentials can be used as a parameter to the proliferative activity, in particular of atypical and malignant meningiomas. METHODS: This study consisted of 47 meningiomas(6 malignant, 14 atypical, and random sampled 27 benign meningiomas). By immunohistochemical staining of Ki-67 and PCNA on formalin-fixed, paraffin-embedded sections, the anti-human rabbit polyclonal antibody against Ki-67 antigen and anti-PCNA monoclonal antibody(PC10) scores were counted. FCM was also performed on paraffin-embedded tissue using a selective staining technique for DNA. DNA ploidy, S-phase fraction, and proliferative index(PI)) were determined. RESULTS: The results are summarized as follows; 1) Proliferation rates as assessed by Ki-67 and PCNA closely correlated with the degree of anaplastic histologic features. 2) Proliferative potentials determined by FCM(S-phase fraction and PI) were not able to distinguish between benign and atypical/malignant meningiomas. 3) DNA ploidy was not a useful indicator of histologic grade in these tumors. 4) Proliferative potentials such as Ki-67 staining index(SI) and PCNA SI did not correlate with the ploidy pattern. 5) There was a linear correlation between Ki-67 SI and PCNA SI, but we could not find a correlation between Ki-67 SI and S-phase fraction or PI. Our results also did not show a statistically signficant correlation between PCNA SI and S-phse fraction or PI. CONCLUSIONS: We conclude that evaluation of the proliferative potentials with Ki-67 and PCNA is important as an additional factor for the prediction of malignancy in meningiomas. A dual study of Ki-67 and PCNA SIs on the same tissue might improve the accuracy with which the proliferative potential of a tumor can be predicted. We demonstrated that FCM in meningiomas is not valuable in predicting the behavior of these neoplasms, but we did observe a trend toward more malignancy with higher percent S-phase fraction and higher PI. Analysis of the S-phase fraction and PI might therefore be a useful tool to discriminate among histologic grades of meningiomas.
DNA ; Flow Cytometry* ; Ki-67 Antigen ; Meningioma* ; Ploidies ; Proliferating Cell Nuclear Antigen*

To characterize cellular responses during hepatic regeneration, we examined 13 explant livers and 5 liver allografts by immunohistochemistry for cytokeratin 7, HepPar1, CD68, alpha-smooth muscle actin (alpha-SMA) and proliferating cell nuclear antigen as well as reticulin and Masson-trichrome staining. Within a week after liver damage, elongated CD68-positive cells were detected along the border of necrotic area. The number of alpha-SMA-positive cells was slightly increased along the sinusoids. Ductular proliferation or fibrosis was negligible. After one or two weeks, the size and number of CD68-positive cells were markedly increased. alpha-SMA-positive cells increased in number within lobules and portal tracts. Ductular proliferation occurred predominantly at the limiting plate or along the border of necrotic areas. After one month, necrotic parenchyma was replaced by many ductules, CD68-positive cells, alpha-SMA-positive cells. Nodules of regenerating hepatocytes and irregular fibrosis were diffusely present. Other nonparenchymal cells were not significantly changed. These observations indicate that chronological interaction between nonparenchymal and parenchymal cells occur during the course of human hepatic regeneration and suggest extensive porto-periportal fibrosis more than a few months after the onset of fulminant hepatitis is a major indicator of chronic functional impairment necessitating liver transplantation.
Actins/analysis ; Antigens, CD/analysis ; Antigens, Differentiation, Myelomonocytic/analysis ; Human ; Immunohistochemistry ; Keratin/analysis ; Liver/*cytology ; *Liver Regeneration ; Proliferating Cell Nuclear Antigen/analysis

BACKGROUND: CD44 is a polymorphic family of transmembrane glycoproteins generated by alternative splicing of messenger RNA and is involved in the mechanism of tumor invasion and metastasis. METHODS: The expression of selected CD44 molecules (CD44s, CD44v5, and CD44v6) was determined immunohistochemically in 84 cases of non small cell lung carcinomas (NSCLCs). The results were compared with PCNA index, microvessel density (MVD), and clinicopathological parameters including patient? survival. RESULTS: CD44s showed a positive reaction in 61.9% (52/84) of NSCLCs, CD44v5 in 73.8% (62/84), and CD44v6 in 39.3% (33/84). Squamous cell carcinomas (SCCs) displayed preferential expression of all CD44 molecules in comparison with adenocarcinomas (ACs) (p<0.001). As a whole, the expression of CD44 molecules was not correlated with clinical parameters (stage, TNM-T, and TNM-N), PCNA index, or MVD. For ACs only, however, CD44v5 expression was negatively correlated with PCNA index (p<0.05). Poor survival was correlated with CD44v5 expression in ACs and CD44v6 in SCCs (both, p<0.05). CONCLUSIONS: These findings suggest that CD44 molecule in NSCLC could be a distinctive phenotypic marker for SCC, and the possibility that CD44v5 and CD44v6 are in some way instrumental in conditioning the biologic behavior of NSCLC according to major histologic types.
Adenocarcinoma ; Alternative Splicing ; Antigens, CD34 ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Glycoproteins ; Humans ; Microvessels ; Neoplasm Metastasis ; Proliferating Cell Nuclear Antigen ; RNA, Messenger

To better understand the relationship between specific chromosome changes found in human lung tumors and their phenotypic consequences a the tissue level, an in situ hybridization (ISH) procedure of chromosome 17 and immunohistochemistry of proliferating cell nuclear antigen (PCNA) were done. The deparaffinized sections were stained with pericentromeric probes for chromosome 17 and an immunohistochemical study of a monoclonal antibody against PCNA were performed. The numbers of chromosome signals were than compared with the positivity of PCNA expression. The mean numbers of chromosome were 1.62 in normal lymphocytes and 2.48 in lung cancer cells. Tumors showed a high mean positivity of PCNA of 43.4%. Mean PCNA expression was higher in squamous carcinomas than in adenocarcinomas (p<0.05). A linear correlation between numbers of ISH signals and PCNA expression was not demonstrated, but there was a tendency of increasing PCNA positivity according to increasing numbers of ISH signals in adenocarcinomas of the lung and the tumor tissues which were over 50% positive PCNA expression. There was no linear correlation between numbers of ISH signals, PCNA positivity and tumor stages, and keratinization of squamous cell lung cancer. These results suggest that ISH will prove to bo an important tool for determining the underlying genetic basis for tissue phenotypic heterogeneity by allowing genetic determinations to be made on paraffin-embedded tissue sections where histologic architecture is preserved, and immunohistochemical nuclear staining with anti-PCNA on routinely processed tissue is a simple technique for the assessment of proliferation in non-small cell lung carcinoma.
Antigens, Neoplasm/analysis ; Cell Differentiation/physiology ; Cell Division/physiology ; Chromosome Aberrations/*physiology ; *Chromosomes, Human, Pair 17 ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lung Neoplasms/*genetics/pathology ; Neoplasm Staging ; Nuclear Proteins/analysis ; Phenotype ; Proliferating Cell Nuclear Antigen

The proliferative activity of human gastric carcinoma was measured by means of in vitro incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), into the newly-synthesized DNA of fresh tumors and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) using avidin-biotin peroxidase method. Eighty-two cases of surgically resected human gastric carcinomas consisting of 18 various histologic types were subjected to study. The mean BrdU labelling index (LI) and PCNA LI were 22.9% and 39.1%, respectively. The correlation between BrdU LI and PCNA LI was statistically significant (correlation coefficient mu = 0.61334, p = 0.0001). We concluded that immunohistochemical staining for PCNA may become a practical method instead of in vitro or in vivo BrdU labeling to assess the proliferation fraction of the gastric cancer patient.
Antibodies, Monoclonal ; Antigens, Neoplasm/*metabolism ; Bromodeoxyuridine/*metabolism ; Carcinoma/*metabolism/pathology ; Cell Division ; DNA Replication ; DNA, Neoplasm/biosynthesis ; Humans ; Immunoenzyme Techniques ; Nuclear Proteins/*metabolism ; Proliferating Cell Nuclear Antigen ; Stomach Neoplasms/*metabolism/pathology ; Tumor Cells, Cultured

Various methods were used to estimate the proliferative activity of tumor cells, including the Ki-67 labeling index, proliferating cell nuclear antigen the Brdurd labeling technique, the mitotic index, and flow cytometric analysis. Several recent reports have indicated that these parameters of cellular proliferation may be of some prognostic significance. In this study, cellular proliferative activities in 105 gastric cancer patients were analyzed with various clinicopathologic factors by using the ki-67 labeling index. The monoclonal antibody to the Ki-67 antigen detects a nuclear antigen expressed in all phases of the cell cycle except G0, and has been widely used to determine the proliferative activity of neoplastic tissues. The Ki-67 labeling index (the number of Ki-67 positive tumor cells divided by the sum of Ki-67 positive and negative tumor cells) was derived by counting 1,000 cells in each case. A significant difference was noted between advanced and early gastric cancer. Advanced gastric cancer lesions showed a mean value of 32.15, about 1.7 times greater than that of the early gastric cancer lesions, 18.32 (p=0.001). The presence or absence of lymph node metastasis also showed a significant difference. The mean value of Ki-67 with lymph node metastasis was 31.78 whereas that without metastasis was 19.48 (p=0.001). There was also a significant difference in Ki-67 LI between each stage (p=0.010). However, no statistically significant differences were noted in age, sex, tumor location, histological differentiation, lauren type, and tumor size. Conclusion : High Ki-67 LI may suggest active cellular proliferation and increased risk of advanced cancer and lymph node metastasis. Ki-67 LI may be used as a possible independent parameter to predict the outcome of gastric cancer treatment.
Cell Cycle ; Cell Proliferation ; Humans ; Ki-67 Antigen ; Lymph Nodes ; Mitotic Index ; Neoplasm Metastasis ; Proliferating Cell Nuclear Antigen ; Stomach Neoplasms*

PURPOSE: To compare the proliferation potential of the epithelial cells between unicystic ameloblastoma (UA), dentigerous cyst (DC), and odontogenic keratocyst (OKC) and to correlate this proliferation potential with the radiographic features of these three pathoses. MATERIALS AND METHODS: Immunohistochemical expression of PCNA, Ki-67, and cytokeratin as a proliferation marker were assessed for 15 cases of UA, 15 cases of DC, and 15 cases of OKC. The degree of immunochemical expression of three proliferation markers were correlated with the radiographic features, especially cortical expansion (negative and positive) and shape of border (scalloped and round). RESULTS: Using PCNA and Ki-67, OKC showed the highest proliferation potential and UA the lowest. Statistically significant differences were found between the OKC and the UA (p< 0.05). However, no statistically significant difference was present according to the radiographic features in all pathoses. Using cytokeratin, there was no significant differences of proliferation potential among three pathoses. CONCLUSIONS: OKC epithelium has the most intense proliferation potential, followed by the dentigeous cyst and then unicystic ameloblastoma. There is no significant relation between the radiographic features and the proliferation potential of epithelium of these three pathoses.
Ameloblastoma* ; Dentigerous Cyst* ; Epithelial Cells ; Epithelium ; Keratins* ; Ki-67 Antigen ; Odontogenic Cysts* ; Odontogenic Tumors ; Proliferating Cell Nuclear Antigen*

Animals ; Epstein-Barr Virus Nuclear Antigens ; immunology ; Immunization ; Mice ; Mice, Inbred BALB C ; Viral Matrix Proteins ; immunology ; Viral Vaccines