Detailed mechanism of uterine cervical cancer progression still remains unclear. Altered programmed cell death (apoptosis) and cellular proliferation are associated with the development of neoplasia. The authors investigated the expressions of bcl-2, which inhibit apoptosis, and caspase-3, which is involved in the induction of apoptosis and has been considered to be correlated with apoptosis, and proliferating activity according to the degree of malignancy in the squamous neoplasia of the uterine cervix. Correlation between bcl-2 and caspase-3 expression and proliferating activity was done. The materials were low grade squamous intraepithelial lesions (LSIL, n=15), high-grade squamous intraepithelial lesions (HSIL, n=15), microinvasive squamous cell carcinoma (n=15), and squamous cell carcinoma (n=15). Immunohistochemical stainings for bcl-2, caspase-3, and MIB-1 were done. bcl-2 and MIB-1 expressions were progressively increased in accordance with the increasing degree of malignancy, but caspase-3 immunoreactivity was higher in LSIL than invasive cancers. There was an inverse relationship between bcl-2 and caspase-3 expression, but the difference did not reach statistical significance. No significant correlation between MIB-1, bcl-2, and caspase-3 expressions was observed. These results suggest that an inhibition of apoptosis and the augmentation of proliferating activity of tumor cells might be separately involved in the development of the cervical squamous neoplasia.
Apoptosis ; Carcinoma, Squamous Cell ; Caspase 3* ; Cell Death ; Cell Proliferation ; Cervix Uteri* ; Female ; Uterine Cervical Neoplasms

Estrogen and progesterone receptors exist in the epithelial and stromal cells of the endometrium. Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions of estrogen and progesterone in epithelial and stromal cells. This study was performed to evaluate the differences estrogen and progesterone receptor(ER/PR) expression in the epithelial and stromal cells of endometrial hyperplasias and adenocarcinomas using immunohistochemical methods. Immunohistochemical analysis of proliferating cell nuclear antigen(PCNA) was done to evaluate a possible correlation between PCNA and hormone receptor expression. Evaluation was based on samples from 31 simple hyperplasias, 30 complex hyperplasias, and 32 adenocarcinomas. The immunohistochemical expression of ER, PR and PCNA in epithelial and stromal cells were examined according to a scoring system based on the percentage of positive cells and the staining intensity. The results were as follows; 1) The expression of ER and PR in epithelial cells showed a graded, significant decreases in simple hyperplasia, complex hyperplasia and endometrial carcinoma, in that order(ER: P=0.008, PR: P= 0.026). 2) PR expression in the stromal cells showed a significant decrease between hyperplasia and adenocarcinoma(P=0.003). The difference in ER expression was not significant. 3) In stromal cells, the decrease in PR expression was more prominent than the decrease in ER expression when complex hyperplasia was compared to simple hyperplasia. 4) The PCNA expression in simple and complex hyperplasia and adenocarcinoma was not higher than the expression of PCNA in nomal proliferative endometrium. There was no significant difference in PCNA expression between simple and complex hyperplasia and adenocarcinoma(P=0.073). 5) A negative correlation between PCNA and ER/PR expression was not demonstrated in simple and complex hyperplasia, or in adenocarcinoma. Endometrial hyperplasia and adenocarcinoma are probably related to a paracrine action of estrogen and progesterone in epithelial and stromal cells. A progressive loss of PR expression in stromal cells may induce abnormal proliferation of endometrium due to a disrupted hormonal balance.
Adenocarcinoma

Hepatocellular carcinoma (HCC) is malignant tumor frequently occurring in Koreans. There have been few reports regarding the cytologic findings of fine needle aspiration (FNA) of HCC. Most have suggested a diagnostic problem in the cytology distinguishing HCC from some benign hepatic lesions-for example, a regeneration nodule in cirrhosis and liver cell adenoma. In spite of its high frequency in Korea, no cytologic study has been reported, concerning the FNA of HCC. In an attempt to achieve cytologic criteria for the diagnosis of HCC, the authors studied retrospectively cytopathologic findings of 247 cases of HCC. These cases were confirmed either by histologic examination including lobectomy, biopsy, or cell block materiai, or, when tissue diagnosis was unavailable, by a high serum alpha-fetoprotein level (over 400 l. U.). All aspiration smears were stained by the Papanicolaou method. In each case, the smears were analyzed for cell patterns and various cytomorphology of the tumor cells. The smear background was assessed for the presence of tumor cell necrosis and inflammatory components and compared to that of metastatic carcinomas. The cell patterns were classified as trabecular, acinar, dispersed, and irregular. The cytologic parameters analyzed included the degree of nuclear atypia and the presence of mitoses, intranuclear cytoplasmic inclusions, nucleolar prominency, endotheiial lining, multinucleated giant cells, eosinophiic globules, bile, and Mallory body.Most of the FNA of HCC showed markedly cellular smears. The tumor cells were most frequently arranged in a trabecular pattern (80.3%). The irregular (12.6%), the acinar (5.5%), and the dispersed patterns (1.7%) followed in decreasing frequency. Individual hepatoma cells were larger than normal liver cells. However, they had morphologic features characteristic of the hepatic cells: the cells were round or polygonal, their cytoplasm was abundant and granular with eosinophilic or amphophilic stainability, and their nuclei were round to oval, located centrally, and tended to have prominent nucleoli. Anaplasia and pleomorphism of tumor cells were generally mild to moderate. These findings existed even in very well differentiated cases. Mitotic figures were present in about 85% of the cases. Prominent nucleoli were observed only in about half the cases. The frequency of other cytologic features was as follows: intranuclear cytoplasmic inclusion in 86.8%; endothelial lining in 56.1%: bile in 19.8%; and giant cells in 60.1%. Clear cells were often present in11.7%, Most aspiration smears of HCC displayed clean background without necrosis or inflammatory material in contrast to the dirty, necrotic background of metastatic cancers and cholangiocarcinomas. Based on the above mentioned features, it is suqqested that the cytologic critieria most important for the diagnosis of HCC include a markedly cellular smear, trabecular pattern, hepatocytoid appearance of tumor cells, endothelial lining, the presence of bile, giant cells, intranuclear cytoplasmic inclusions, and prominent nucleoli, Among these, trabecular pattern, endothelial lining, giant cells and clean smear background are points to be considered in differentiating HCC from metastatic and cholangiocellular carcinoma.
Adenoma, Liver Cell ; alpha-Fetoproteins ; Anaplasia ; Bile ; Biopsy ; Biopsy, Fine-Needle ; Carcinoma, Hepatocellular ; Child* ; Cholangiocarcinoma ; Cytoplasm ; Diagnosis ; Endothelial Cells ; Eosinophils ; Fibrosis ; Giant Cells ; Glomerulonephritis* ; Hepatocytes ; Humans ; Inclusion Bodies ; Korea ; Liver ; Mitosis ; Necrosis ; Regeneration ; Retrospective Studies

The effect of androgen in the development of the normal prostate and the evolution of benign prostatic hypertrophy (BPH), and prostatic adenocarcinoma has been proven. In addition to androgen, estrogen and progesterone are also thought to play a role in the pathogenesis of BPH and carcinoma. However, their exact roles are not yet known because there is no conclusive evidence. Thirty cases of prostatic adenocarcinoma and 16 cases of BPH were studied. Immunohistochemical staining for estrogen receptor (ER) and progesterone receptor (PR) in epithelial and stromal cells, respectively was performed and the results were assessed semiquantitatively based on the number of positive cells per 100 total cells. Slides were scored as negative; less than 5% of cells, 1 ; 6~15% of cells, 2 ; 16~25% of cells, and 3 ; more than 26% of cells. The relationship between ER and PR expression and the patient's age, histologic grade, and clinical stage was evaluated in prostatic adenocarcinomas. ER was negative in epithelial and in stromal cells for all prostatic adenocarcinomas and BPH cases. The PR expression in epithelial cells and in stromal cells of BPH was noted in 15 (93.8%) and 16 (100.0%) out of 16, respectively. The PR expression of carcinoma cells and stromal cells in prostatic adenocarcinoma was found in 28 (93.3%) and 23 out of 30 (76.7%), respectively. The PR immunoreactivities of stromal cells around carcinoma were 3 in 18 cases, 2 in one case, and 1 in 4 cases, but those of epithelial and stromal cells of BPH and carcinoma cells of prostatic carcinoma were similar to each other with a value of 3 in most cases. The PR expression rate of stromal cells around carcinoma was significantly correlated with the patient's age (p=0.044), but not with histologic grade and clinical stage. In summary, estrogen does not have a direct effect on the biological behavior of BPH and prostatic adenocarcinoma, but progesterone appears to play a role in the pathogenesis of BPH and prostatic adenocarcinoma. Further studies should clarify the biological role of progesterone in the human prostate.
Adenocarcinoma* ; Epithelial Cells ; Estrogens* ; Humans ; Progesterone* ; Prostate ; Prostatic Hyperplasia* ; Receptors, Progesterone* ; Stromal Cells

The glandular lesions of the uterine cervix can be classified into endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and adenocarcinoma, but the diagnostic criteria and the continuity of endocervical glandular lesions are still controversial. The aim of this study was to evaluate the significance of immunohistochemical findings of p53 and MIB-1 in the discrimination and the continuity of EGD, AIS and adenocarcinoma. The materials for the study included 11 cases of adenocarcinoma, 7 cases of AIS, 12 cases of high grade EGD, and 19 cases of low grade EGD. Also included were eleven benign glandular lesions (5 cases of tuboendometrial metaplasia, 3 cases of mesonephric remnant, 3 cases of microglandular hyperplasia). A strong reaction of more than 5% of the glandular epithelial nuclei was interpreted as positive for p53 protein. MIB-1 expression was analyzed semiquantitatively as negative, 1 , 2 , 3 , depending on the percentage of positive nuclei (less than 1%, 1~9%, 10~39%, > or = 40%, respectively). p53 protein expression was found in 3 (27.3%) out of 11 cases of adenocarcinoma, and 2 (28.6%) out of 7 cases of AIS. But all of high and low grade EGD cases were negative. High MIB-1 labelling index (> or =10%) was found in all adenocarcinoma cases and in 3 (42.9%) out of 7 cases of AIS. But only 2 (17.7%) out of 12 cases of high grade EGD showed high MIB-1 labelling index, and all of low grade EGD and benign lesions showed negligible MIB-1 positivities. In summary, MIB-1 labelling index might be valuable in the discrimination of malignant glandular lesions and endocervical glandular dysplasia from benign lesions, but p53 expression could be a useful parameter in the discrimination of malignant glandular lesions from endocervical glandular dysplasia and benign lesions.
Adenocarcinoma ; Cervix Uteri* ; Discrimination (Psychology) ; Female ; Metaplasia

This study was aimed to elucidate the relationship between combinations of treadmill speed-grade and oxygen consumption(Vo2). Twenty athetic and 20 non-athletic male college students aged 19-24yr were employed to exercise on a treadmill using 4 speeds(4.02, 5.47, 6.76 and 8.05km/h) and 5 grades(0, 8, 12, 16 and 20%). A fixed speed was selected for each session with the grade increased every 3 min. The Vo2, heart rate, stride frequency and stride length were measured during the last min of each 3-min stage. Vo2increased linearly with increasing speed and grade showing significant multiple correlations in nonathletes(Vo2=3.64x+0.831y+0.031xy-7.03, R=0.98, P<0.01) and athletes(Vo2=3.48x+0.324y+0.112xy-5.74, R=0.99, P<0.01). Stride frequency and length tended to increase with increasing speed except for the transition from walking to runnig at 8.05Km/h at which the stride frequency ran up much higher with the stride length getting lower than at 6.76Km/h. Heart rate increased linearly with increasing Vo2. The rate of increase was higher during walking than during running. These results indicate that athletes have higher rate of increase in Vo2than nonathletes at near-maximal exercise and may be used as a guideline in predicting maximum oxygen comsumption and in prescribing exercise intensity.
Athletes* ; Heart Rate ; Humans ; Male ; Oxygen Consumption* ; Oxygen* ; Running ; Walking

Heat shock protein of 72 kDa (HSP70) has a role in the functional modulation of sex steroid hormone receptors and in p53-associated oncogenesis and inhibits apoptosis associated with bcl-2. However, the exact role of HSP70 in the development of endometrial adenocarcinoma has not been well established. The aim of this study is to evaluate the role of HSP70 in relation with ER, PR, p53 and bcl-2 expressions and apoptosis in benign and malignant endometrial lesions. Immunohistochemical studies for HSP70, ER, PR, p53, bcl-2 and TUNEL method for apoptosis were performed in 30 cases of adenocarcinoma and 30 cases of benign endometrial lesions consisted of each 10 cases of disordered proliferative endometrium (DP), simple or complex hyperplasia (HP), and atypical hyperplasia (AH). There were no significant differences of HSP70 and bcl-2 expression rates and apoptotic index (AI) between DP, HP, AH, and adenocarcinoma. p53 expression rate in adenocarcinoma was 36.7%, but no p53 expression was identified in DP, HP and AH (p<0.05). In adenocarcinoma, HSP70 expression rate was higher in ER and PR negative adenocarcinoma (p<0.05), and p53 expression rate was higher in nonendometrioid type and FIGO grade II and III (p<0.05), but no significant difference of bcl-2 expression rate according to the histological type and FIGO grade. AI was higher in nonendometrioid type (p<0.05). There was no correlation between HSP70, p53 and bcl-2 expressions, and no significant difference of AI according to HSP70, ER, PR, p53, and bcl-2 expressions. In conclusion, higher HSP70 expression rate in poorly differentiated and ER and PR negative adenocarcinoma suggests that HSP70 inhibits ER and PR expression and may be involved in the development of poorly differentiated endometrial adenocarcinoma.
Adenocarcinoma* ; Apoptosis* ; Carcinogenesis ; Endometrium ; Female ; Heat-Shock Proteins ; Hyperplasia ; In Situ Nick-End Labeling

Angiogenesis is essential for tumor growth and metastasis, however, the prognostic value of neovascularization is undetermined. The aim of this study is to evaluate the prognostic significance of microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in breast carcinomas. An immunohistochemical stains for CD 31 (DAKO) to estimate MVD and VEGF (Santa Cruz) were done on 40 cases of invasive breast carcinoma. MVD was calculated as an average count of vessels per 200 power field in the most vascularized areas. VEGF expression was interpreted according to staining intensity and number of positive cells. Mean MVD was 35, and MVD was not correlated with lymph node metastasis or histologic grade, but high MVD (mean MVD>35) showed an increasing tendency in cases with larger size, negative ER/PR, and positive cathepsin D. All of the cases showed VEGF expression, but VEGF expression was not correlated with tumor size, histologic grade, lymph node metastasis, ER/PR status, and cathepsin D expression. These results suggest that MVD and VEGF expressions are not reliable prognostic factors.
Breast Neoplasms* ; Breast* ; Cathepsin D ; Coloring Agents ; Lymph Nodes ; Microvessels* ; Neoplasm Metastasis ; Vascular Endothelial Growth Factor A*

It is known that the activity of tumor cells correlates with the malignant potential of tumors. Nucleolar organizer regions(NORs) are loops of DNA which occur in nucleoli and which possess ribosomal DNA genes. Ribosomal DNA genes transcribe to ribosomal RNA by RNA polymerase I and are of vital significance in the ultimate synthesis of protein. Proteins associated with the NORs are stained with silver nitrate(Ag-NORs). Ag-NORs were studied in various tumors and might reflect the activity of cells and might be and indicator of the degree of malignancy in tumors. 0.05 % N-Butyl-N(4-hydroxybutyl) nitrosamine(BBN) in drinking water was given for 8 and 14 weeks to induce pre-neoplastic and neoplastic vesical epithelial lesions in female Wister rats. Ag-NORs were stained by the simple one-step silver colloid staining in routine processed, formalin-fixed paraffin sections of bladder lesions induced by N-butyl-N(4-hydroxybutyl) nitrosamine(BBN) in rat. The mean number of silver stained NORs(Ag-NORs) was as follows : normal transitional epithelium was 1.64+/-0.25(mean+/-SD; n=10), simple hyperplasia was 2.24+/-0.24(n=7). nodular hyperplasia was 2.63+/-0.12 (n=6), transitional cell papilloma was 3.24+/-0.28(n=6) and transitional cell carcinoma was 4.52+/-0.32(n=10). Based on the above results, we concluded that the mean number of Ag-NORs showed a stepwise increase from normal transitional epithelium through simple hyperplasia and nodular hyperplasia to papilloma and carcinoma of bladder epithelium induced by BBN in rat and may reflect proliferative activity of cells. Further investigations may be needed to confirm whether the number or quantification of Ag-NORs is a useful method for evaluating proliferative activity of neoplastic lesions or another indicator of prognosis in human bladder cancer.
Animals ; Butylhydroxybutylnitrosamine* ; Carcinoma, Transitional Cell ; Colloids ; DNA ; DNA, Ribosomal ; Drinking Water ; Epithelium ; Female ; Humans ; Hyperplasia ; Nucleolus Organizer Region* ; Papilloma ; Paraffin ; Prognosis ; Rats* ; RNA Polymerase I ; RNA, Ribosomal ; Silver ; Urinary Bladder Neoplasms ; Urinary Bladder*

OBJECTIVE: Diurnal preference is an attribute reflecting whether people are alert and preferring to be active either early or late in the day. It also referred to as chronotype or morningness-eveningness trait. The PER3 genes have been known to influence diurnal preference. In this study, we have investigated the associations between the PER3 gene polymorphisms and diurnal preference in a healthy young population, controlling for the social and environmental confounding factors. METHODS: The participants in this experiment included 299 unrelated medical college students (M=191, F=108), with a mean age of 22.9 years. Diurnal preference was measured by a single administration of the 13-item Composite Scale for Morningness (CSM). Genotyping of the PER3 VNTR (rs57875989) was performed using polymerase chain reaction. A two-tailed alpha of 0.05 was chosen. RESULTS: The mean+/-SD score on the CSM scale for all subjects was 31.90+/-6.39. There was no significant difference in total CSM score between gender groups, although females showed a trend towards higher morningness score. Although PER3 5R/5R showed the tendency towards high CSM scores, there were no significant differences on CSM scores among genotypes and allele status of PER3 VNTR (rs57875989). CONCLUSIONS: We could not confirm that the PER3 VNTR is associated with diurnal preference in a Korean healthy young population. The future studies need to investigate the association between diurnal preference and other polymorphisms of PER3 gene in larger sample of Korean young healthy population.
Alleles ; Female ; Genotype ; Humans ; Polymerase Chain Reaction