• Journal of Chest Surgery
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• v.39 no.5 s.262
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• pp.376-381
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• 2006

Background: The Ki-67 protein is a biomarker associated with cell proliferation and a valuable negative prognostic factor in non-small cell lung cancer. We investigated the Ki-67 protein expression in resected non-small cell lung cancer to evaluate the impact on clinicopathological characteristics and postoperative prognosis. Material and Method: Using monoclonal antibody Ki-67, we immunohistochemically examined 38 surgically resected non-small ceil lung cancers to determine Ki-67 Labeling Index (LI). We analysed the differences of clinicopathological characteristics and postoperative recurrence and survival between High Ki-67 Group $(LI{\ge}20%)$ and Low Ki-67 Group (LI<20%). Result: The Ki-67 LIs were heterogenous and a mean values was $20.0{\pm}20.05%$. There were no significant differences in age, sex, smoking, TNM stage, and vascular invasion between High Ki-67 Group and Low Ki-67 Group. A High Ki-67 Group was significantly associated with squamous cell type, poor differentiation, and lymphatic invasion $(p{\le}0.05)$. High Ki-67 Group showed a trend of lower survival (median 47.2 vs. 90.5 months, p=0.312) and lower disease-free survival (median 18.2 vs. 72.3 months, p=0.327) than Low Ki-67 Group. Conclusion: These results indicate that increased Ki-67 protein expression may be a negative prognostic factor and showed a trend of shortened survival and disease-free survival. To evaluate the pivotal role of Ki-67 protein expression, a long-term follow-up and further study are required.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.821-825
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• 2012

Purpose: Centromere protein H (CENP-H) and Ki67 are overexpressed in some malignancies, but whether they are predictors of survival after primary resection for hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. Methods: We assessed immunohistochemical expression of CENP-H and Ki67 in 112 HSCC specimens collected between March 2003 and March 2005 for analysis by clinical characteristics. The Kaplan-Meier method was used to analyze relapse-free survival and logistic multivariate regression to determine risk factors of relapse-free survival. Cholecystokinin octapeptide assays and flow cytometry were used to examine cell proliferation and apoptosis after siRNA inhibition of CENP-H in HSCC cells. Results: Overall, 50 (44.6%) HSCC specimens showed upregulated CENP-H expression and 69 (61.6%) upregulated Ki67. An increased CENP-H protein level was associated with advanced cancer stage and alcohol history (P=0.012 and P=0.048, respectively) but an increased Ki67 protein level only with advanced cancer stage (P=0.021). Increased CENP-H or Ki67 were associated with short relapse-free survival (P<0.001 or P=0.009, respectively) and were independent predictors of relapse-free survival (P=0.001 and P=0.018, respectively). siRNA knockdown of CENP-H mRNA inhibited cell proliferation and promoted cancer cell apoptosis in vitro. Conclusions: Upregulated CENP-H and Ki67 levels are significantly associated with short relapse-free survival in HSCC. These factors may be predictors of a relapsing phenotype in HSSC cases.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.73-80
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• 2002

Purpose : Tumor growth in a given neoplasm is the net result of cell proliferation and cell loss, and apoptosis is the most significant component of continuous cell loss in most tumors. In this study, we examined non-Hodgkin's lymphoma (NHL, n=67) immunohistochemically for the presence of Bcl-2 oncoprotein and P53 protein and compared apoptotic indices (Als) and Ki-67 proliferative indices (percentages of Ki-67 positive cells). Materials and Methods : 67 patients with NHL were evaluated : 3 low-grade and 64 intermediate-grade. The phenotype was determined in 65 cases : 47 $(70\%)$ were B cell type and 18 $(27\%)$ were T ceil type. Als and Ki-67 proliferative indices were determined immunohistochemically and the overexpression of P53 and Bcl-2 protein were also evalutated. Results : The overexpressions of Bcl-2 protein and P53 protein were found in $40\%$ (26/65) and $31\%$ (20/65). The Al ranged from $0\%\;to\;15\%$ (mean 2.16, median 1.2). Cellular Bcl-2, which counteracts apoptosis, was significantly (p=0.005) associated with Als. Ki-67 proliferative indices ranged from $1\%\;to\;91\%$ (mean 55.4), and P53 was significantly (p=0.000) associated with Ki-67 proliferative indices. A positive correlation between Als and Ki-67 proliferative indices was revealed (p=0.012) in Bcl-2 positive patients. Conclusion : In NHL, we observed a correlation between Als and Bcl-2 expression, between Ki-67 proliferative indices and P53 expression, and between Als and Ki-67 proliferative indices in Bcl-2 positive patients. Our results suggest that cell apoptosis may be inseparable from cell proliferation during tumor growth.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4815-4818
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• 2013

Background: Atrophic epithelium of cervix sampled from postmenopausal women may mimic high-grade cervical intraepithelial neoplasia in Papanicolaou-stained (Pap) smears. Ki-67 (MIB-1) protein presents on proliferating cells, and percentage of cells with positive nuclei provides a reliable tool for rapid evaluation of the growth fraction. The aim of this study was to determine the diagnostic value of protein Ki67 staining in atypical pap smears of postmenopausal women. Methods: In a case-control setting, pap smears of 75 women with an atypical pap smear (case group) and 75 with normal pap smears (controls) were obtained before and after estrogen treatment. Afterward, samples were exposed to the monoclonal antibody Ki-67 (MIB-1) and the immunohistochemically demonstrated Ki-67+ cells were compared. Results: Mean ages of cases and controls were $60.4{\pm}4.5$ and $59.9{\pm}4.3$ years respectively (P=0.50). There was one (2.7%) positive Ki-67 specimen in the case group, without any positive Ki-67 specimen in the control group (P=0.50). Conclusions: Measurement of proliferative activity index in Pap smears restrained with MIB1 is a simple, reliable, and cost-effective method for excluding negatives. This would imply that it might allow a substantial reduction of diagnostic estrogen courses and subsequent Pap smears in postmenopausal women with atypical findings.

• Journal of Chest Surgery
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• v.38 no.12 s.257
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• pp.835-843
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• 2005

Background: Cancer of the esophagus is one of the most malignant tumors with poor prognosis. The p53 gene alteration, over expression of Cyclin D1, and Ki67 index were thought to be the prognostic factors. However, their clinical significances in esophageal squamous cell carcinoma are controversial and p53 accumulation may not correlate with genetic mutation. The current study investigates their prognostic significance in squamous cell carcinoma of the esophagus. Material and Method: The Subjects studied were 124 esophageal squamous cell carcinoma patients who underwent esophagectomy. The mutation of p53, over expression of Cyclin D1, Ki67 labelling index, mitotic index were examined by using an immunohistochemical staining. We compared the results and investigated the correlation with the mutation of p53, overexpression of Cyclin D1, Ki67 labelling index, mitotic index and tumor size, and duration of survival. Result: There was no correlation between the results in immunohistochemical staining according to age, sex, tumor size, Iymph node status, and clinical stage of the disease. Mutant p53 protein was found in 69 cases (55.6$\%$). Median survival time was 21 months in cases with negative for mutant p53 protein and 22 months in positive cases. There was no significant difference in survival (p=0.46). Median survival time was 22 months in cases with negative for Cyclin D1 and 16 months in positive cases (p=0.18). Median and mean survival time was 22 months and 36 months when Ki67 labeling index was 40 or less (102 cases). Median and mean survival was 16 months and 23 months, when Ki67 labeling index was more than 40 (22 cases). There was significant difference in survival rate (p=0.011). Conciusion: Positivity of p53 and cyclin D1 was not useful in predicting the prognosis in our study. There was no significant correlation among mutant p53 protein accumulation, Cyclin D1 over expression, and Ki67 labeling index. However, in several studies, PCR single strand conformational polymorphism analysis of p53 showed a correlation to the prognosis. We thought that there was a significant discordance between p53 gene mutation and mutant p53 protein accumulation. When Ki67 labeling index was more than 40, prognosis was poorer, Ki67 seems to be a prognostic factor in our study. Therefore, we confirmed the possibility of using molecular markers as prognostic factors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1605-1608
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• 2015

Purpose: To investigate the expression of Ki67 protein in papillary thyroid microcarcinoma(PTMC), and to analyze its clinical significance. Materials and Methods: Ki67 protein expression was evaluated in the tissues of 108 human PTMC and 50 other benign papillary hyperplasia of thyroid specimens using immunohistochemistry. Results: The expression intensity of Ki67 in PTMC and benign papillary hyperplasia of thyroid specimens were $1.45{\pm}1.83%$ and $0.46{\pm}0.46%$.The positive expression rates were 46.3% and 14%. There were significant differences between these two groups (p<0.01). There was no significant variation of the expression intensity and positive expression rates of Ki67 in PTMC with gender, age, position of the tumor and the level of TSH pre-operation (p>0.05), but these parameters varied with tumor size, invasion by membrane and cervical lymph node metastasis (p<0.05 or p<0.01). Conclusions: The expression of Ki67 in PTMC was related to tumor size, invasion by membrane and cervical lymph node metastasis, and could be the important indicator for judging clinical progress and estimating prognosis.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.178-184
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• 2004

This research focuses on the overall evaluation of tumor protein (p53) and cell growth marker (Ki-67) in their functions as carcinogenic factors in both a HPV-infected group and in a HPV-noninfected group with the precancerous dysplasia of uterine cervix. Histological grades were determined by the H&E staining and the expression level of p53 and Ki-67 were tested by the immunohistochemistry method. The results were as follows. Among the total of 66 cases, p53 (+) was observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values correlate with the increase of dysplasia intensity in HPV-noninfected group and showed significant correlation (p<0.05), but there were no significant difference from the HPV-infected group. Among a total of 66 cases, the mitotic index of Ki-67 (+) were observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values were significantly different against dysplasia intensity (p<0.05), but showed no significant difference from HPV infection. After cross comparing the statistical parameters of p53 and ki-67 in their significance, p53 was shown to be statistically significant with Ki-67 while there was no statistically significant difference with Ki-67 (p<0.05). Taken together, tumor protein (p53) and an index of Ki-67 observed in cervical dysplasia and in HPV related dysplasia of cervix uterine did not have any notable significance with HPV infection. The incidence rate of p53, however, had some significant correlation with dysplasia while Ki-67 had no particular statistical significance. As a result, p53 and Ki-67 can be considered as effective diagnostic markers in predicting the disease progression of dysplasia to cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2133-2137
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• 2012

Objective: To investigate the prognostic role of antigen KI-67 (Ki-67) and G1/S-specific cyclin-D1 (cyclin-D1) in patients with laryngeal squamous cell carcinoma (LSCC). Methods: Immunohistochemical staining (IHS) was used to determine the protein expression of Ki-67 and cyclin-D1 in LSCC tissues. Kaplan-Meier survival curves was calculated with reference to Ki-67 and cyclin-D1 levels. Results: Cyclin-D1 and Ki67 were expressed in the nuclei of cancer cells. Among the total of 92 cancer tissues examined by immunohistochemistry, 60 (65.22%) had cyclin-D1 overexpression and 56 (60.87%) had Ki67 overexpression. Cyclin-D1 overexpression is associated with the advanced stage of the cancer (P=0.029), but not with gender, age, stage of cancer, histological differentiation, anatomical site, smoking history and alcohol consumption history. Ki67 overexpression is not associated with the advanced stage, gender, age, histological differentiation, anatomical site, smoking history and alcohol consumption history. A statistically significant correlation was found between lymph node status and the expression of Ki67 (p = 0.025). Overexpression of cyclin-D1 was correlated to shorter relapse-free survival period (P<0.001). Conclusions: Overexpression of cyclin-D1 can be used as a marker to predict relapse in patients with LSCC after primary curative resection.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.241-248
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• 2007

To clarify the growth mechanisms of thyroid tumors, we investigated apoptotic cells in 88 thyroid tumors, consisting of 24 adenomas, 58 papillary thyroid carcinomas, and 6 undifferentiated carcinoma, using terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate digoxigenin-nick end labeling (TUNEL). The cell proliferating marker was also evaluated immunohistochemically using the monoclonal antibody to Ki-67 antigen (MIB-1) in the same tumors. The apoptosis was expressed as a percentage of the TUNEL-positive cells in the tumor cells, and a proliferating marker, being the percentage of Ki-67 positive cells, was counted up each tumor. The statistical analysis were used analysis of variance (ANOVA) and student's t-test that were analyze the differences in the rate of each histological types of the thyroid tumors. The overall level of apoptosis was extremely low in all histological types of the thyroid tumors analyzed, the mean apoptosis being $0.31{\pm}0.40$ in adenoma, $0.55{\pm}0.48 $in papillary thyroid carcinoma, and $4.60{\pm}3.27$ in undifferentiated carcinoma. The Ki-67 protein in the thyroid tumor subtypes was significantly lower in adenoma and papillary carcinoma, at $2.45{\pm}2.99$ and $6.27{\pm}4.42$, respectively, than that in undifferentiated carcinoma at $26.47{\pm}23.88$ (p<0.0001). There was no correlation between clinicopathological factors and apoptosis or Ki-67 in papillary thyroid carcinoma. In conclusion, our findings suggest that apoptosis occurs infrequently in thyroid tumor, and that cell proliferating maker Ki-67 markedly differs according to the thyroid tumor subtypes. Moreover, the ratio between proliferating cells and apoptotic cells may reflect thyroid tumor progression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4897-4902
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• 2014

Purpose: To investigate the anticancer effects and underlying mechanisms of parthenolide on HepG2 human hepatocellular carcinoma cells. Materials and Methods: Cell viability was assessed by MTT assay and cell apoptosis through DAPI, TUNEL staining and Western blotting. Monodansylcadaverin(MDC) and AO staining were used to detect cell autophagy. Cell proliferation was assessed by Ki67 immunofluorescence staining. Results: Parthenolide induced growth inhibition in HepG2 cells. DAPI and TUNEL staining showed that parthenolide could increase the number of apoptotic nuclei, while reducing the expression of the anti-apoptotic protein Bcl-2 and elevating the expression of related proteins, like p53, Bax, cleaved caspase9 and cleaved caspase3. Parthenolide could induce autophagy in HepG2 cells and inhibited the expression of proliferation-related gene, Ki-67. Conclusions: Parthenolide can exert anti-cancer effects by inducing cell apoptosis, activating autophagy and inhibiting cell proliferation.