• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5319-5323
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• 2015

Background: The purpose of this study was to evaluate the prognostic significance of Ki-67 and subjective microvascular density (SMVD) indexes together with other factors in patients with oligodendroglioma. Materials and Methods: In this retrospective study, oligodendroglioma specimens obtained from twenty-five consecutive patients were evaluated for Ki-67 and SMVD indices to help determine histological grading and investigate the fidelity of these markers in clinical prognosis. Other potentially prognostic factors were Karnofsky performance scale, tumor histological grade, and adjuvant radiotherapy. Results: The Ki-67 proliferation index appeared to have a strong correlation with the grade of the tumor and the survival. Age, gender, adjuvant radiotherapy, surgical resection type (complete versus incomplete) did not have any influence on recurrence. The SMVD index correlated significantly with the 3 to 5-year survival. Conclusions: Ki-67 and MVD indexes are important and useful markers in estimating the prognosis of oligodendrogliomas.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2559-2564
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• 2016

Purpose: To compare Ki-67 index and microvessel density MVD) in multiple myeloma and non-myeloma patients and their correlation with each other and other prognostic markers. Materials and Methods: Forty patients were enrolled in this study between 2011-2013, 30 with multiple myelomas and 10 with non-malignant disease as controls. Proliferative activity was analyzed by Ki-67 and microvessel density (MVC) was assessed by CD34 and compared between two groups. In myeloma patients, correlation between Ki-67, MVD and other prognostic factors was assessed by Pearson correlation coefficient. Results: According to Durie Salmon staging criteria, 13 patients were of stage 1, 5 of stage II and 12 of stage III. Ki-67 expression showed a positive correlation with MVD (r=0.729, p<0.001) and was significantly higher (p<0.0001) in myeloma patients (range 35-80%, mean 60.1 %) as compared to controls (range 8-25%, mean 18.1%). $MVD/mm^2$ was also significantly (p<0.0001) higher in myeloma patients (range $62-237/mm^2$, mean $178.0/mm^2$) than controls (range $5.2-50/mm^2$, mean $18.3/mm^2$). Ki-67 and MVD, both increased progressively with increasing stage of myeloma. Ki-67 showed significant positive correlation with blood urea and lactate dehydrogenase and a significant negative correlation with serum albumin. MVD showed a significant positive correlation with blood urea, lactate dehydrogenase, serum creatinine, ${\beta}2$ microglobulin and skeletal lesions. Conclusions: Ki-67 and MVD are indicators of aggressiveness and poor prognosis having significant correlation with each other and other prognostic markers of multiple myeloma. Routine assessment of these markers may help to identify high risk patients, who may benefit from with more aggressive therapy.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.91-96
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• 2006

Purpose: Cancer is a genetic disease caused by alterations in key regulators of cell growth and cell turnover, We investigated apoptotic cell death and cell proliferation in gastric adenomas and adenocarcinomas. Materials and Methods: The TdT-mediated dUTP-biotin nick end labelling (TUNEL) method and immunohistochemistry for Ki-67 were peformed, using paraffin-embedded tissues of 41 gastric adenomas and 100 gastric adenocarcinomas. These results were compared with histopathologic parameters. Results: The Ki-67 labelling index was higher in adenocarcinomas than in adenomas and the apoptotic index was higher in adenomas than in adenocarcinomas. There were no significant difference between the apoptotic index/Ki-67 labelling index and clinicopathological parameters. Conclusion: We propose that cell proliferation is more closely associated with gastric adenocarcinomas than apoptosis is, but that neither has any clinical significance as a prognostic factor in gastric adenocarcinomas. (J Korean Gastric Cancer Assoc 2006;6:91-96)

• 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.

• Journal of Korean Neurosurgical Society
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• v.30 no.7
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• pp.861-869
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• 2001

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.

• The Korean Journal of Nuclear Medicine
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• v.34 no.6
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• pp.465-477
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• 2000

Purpose: Thallim-201 ($^{201}Tl$) brain SPECT and proton ($^1H$) magnetic resonance spectroscopy (MRS) have been used to evaluate tumor grade and viability of glioma. We assessed the correlations between $^{201}Tl$ brain index or spectrum of metabolites of $^1H$ MRS and grade of glioma or histopathologic findings. Materials and Methods: We studied 17 patients (4 astrocytoma, 7 anaplastic astrocytoma and 6 glioblastoma). On $^{201}Tl$ Brain SPECT, $^{201}Tl$ index was measured as the ratio of average counts for region of interest to those for the contralateral normal brain. On $^1H$ MRS, we calculated choline (Cho) /creatine (Cr) ratio and N-acetylaspartate (NAA)/Cr ratio in ROI defined as tumor center. Histopathologic findings were graded by Ki-67 index, cellularity, mitosis, pleomorphism, necrosis and endothelial proliferation. An unpaired t test and statistical correlations were performed to evaluate these data. Results: Tl-index showed the best correlation with Ki-67 index (p<0.01), less correlations with cellularity, mitosis, and endothelial proliferation, but no correlation with results of MRS, pleomorphism, or necrosis. The findings of MRS did not correlate with all of the above. The cases of glioblastoma demonstrated a higher Tl-index, Cho/cr ratio, Ki-67 index and lower NAA/Cr ratio, albeit without statistical significance. Conclusion: Even though $^{201}Tl$ brain SPECT did not correlate directly with grade of malignancy, it may still be useful in determining biological aggressiveness of tumor and prognosis of patients because it correlated well with Ki-67 index, a growth fraction of glioma, cellularity, mitosis and endothelial proliferation.

• Journal of Gastric Cancer
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• v.11 no.3
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• pp.173-179
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• 2011

Purpose: It is difficult to obtain biopsies from gastrointestinal stromal tumors (GISTs) prior to surgery because GISTs are submucoal tumors, despite being the most common nonepithelial neoplasms of the gastrointestinal tract. Unlike anatomic imaging techniques, PET-CT, which is a molecular imaging tool, can be a useful technique for assessing tumor activity and predicting the malignant potential of certain tumors. Thus, we aimed to evaluate the usefulness of PET-CT as a pre-operative prognostic factor for GISTs by analyzing the correlation between the existing post-operative prognostic factors and the maximum SUV uptake (SUVmax) of pre-operative 18F-fluoro-2-deoxyglucose (FDG) PET-CT. Materials and Methods: The study was conducted on 26 patients who were diagnosed with gastric GISTs and underwent surgery after being examined with pre-operative FDG PET-CT. An analysis of the correlation bewteen (i) NIH risk classification and the Ki-67 proliferation index, which are post-operative prognostic factors, and (ii) the SUVmax of PET-CT, which is a pre-operative prognostic factor, was performed. Results: There were significant correlations between (i) SUVmax and (ii) Ki-67 index, tumor size, mitotic count, and NIH risk group (r=0.854, 0.888, 0.791, and 0.756, respectively). The optimal cut-off value for SUVmax was 3.94 between "low-risk malignancy" and "high-risk malignancy" groups. The sensitivity and specificity of SUVmax for predicting the risk of malignancy were 85.7% and 94.7%, respectively. Conclusions: The SUVmax of PET-CT is associated with Ki-67 index, tumor size, mitotic count, and NIH classification. Therefore, it is believed that PET-CT is a relatively safe, non-invasive diagnostic tool for assessing malignant potential pre-operatively.

• Journal of Korean Neurosurgical Society
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• v.49 no.1
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• pp.26-30
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• 2011

Objective: The primary objective of this study was to perform a retrospective evaluation of the radiological and pathological features influencing the formation of peritumoral brain edema (PTBE) in meningiomas. Methods: The magnetic resonance imaging (MRI) and pathology data for 86 patients with meningiomas, who underwent surgery at our institution between September 2003 and March 2009, were examined. We evaluated predictive factors related to peritumoral edema including gender, tumor volume, shape of tumor margin, presence of arachnoid plane, the signal intensity (SI) of the tumor in T2-weighted image (T2WI), the WHO histological classification (GI, GII/GIII) and the Ki-67 antigen labeling index (LI). The edema-tumor volume ratio was calculated as the edema index (EI) and was used to evaluate peritumoral edema. Results: Gender (p=0.809) and pathological finding (p=0.084) were not statistically significantly associated with peritumoral edema by univariate analysis. Tumor volume was not correlated with the volume of peritumoral edema. By univariate analysis, three radiological features, and one pathological finding, were associated with PTBE of statistical significance: shape of tumor margin (p=0.001), presence of arachnoid plane (p=0.001), high SI of tumor in T2WI (p=0.001), and Ki-67 antigen LI (p=0.049). These results suggest that irregular tumor margins, hyperintensity in T2WI, absence of arachnoid plane on the MRI, and high Ki-67 LI can be important predictive factors that influence the formation of peritumoral edema in meningiomas. By multivariate analysis, only SI of the tumor in T2WI was statistically significantly associated with peritumoral edema. Conclusion: Results of this study indicate that irregular tumor margin, hyperintensity in T2WI, absence of arachnoid plane on the MRI, and high Ki-67 LI may be important predictive factors influencing the formation of peritumoral edema in meningiomas.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3903-3909
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• 2016

Purpose: To evaluate the expression of Her2/neu and Ki-67 in benign and malignant gallbladder lesions, and to establish correlations with clinico-pathologic parameters. Materials and Methods: A retrospective analysis was conducted on formalin fixed paraffin embedded (FFPE) benign (n=25) and malignant gallbladder (n=25) tissue samples. Hematoxylin and eosin stained slides of each case were reviewed for: type of malignancy (whether adenocarcinoma, squamous cell carcinoma, or any other type), grade (well, moderate, and poor), depth of invasion, pre-neoplastic changes in adjacent mucosal epithelium like metaplasia and dysplasia. Immunohistochemistry for Her 2 neu and Ki-67 was performed and data analysis was conducted using SPSS 17 software. Chi-square test was used to compare categorical/dichotomous variables. P value of ${\leq}0.05$ was considered significant. Results: The difference of Her 2 neu expression and Ki67 index between benign and malignant groups was found to be statistically significant. Her2/neu positivity did not have any significant correlation with various clinicopathological parameters other than liver involvement. 5 cases of gallbladder cancer showed both Her2/neu and Ki67 positivity. Ten cases were Ki67 positive but Her2/neu negative while one case was Her2/neu positive but Ki67 negative. Conclusions: The present study demonstrated overexpression of Her2/neu and Ki67 in gallbladder cancer. A trend of decreasing Her2/neu expression with increasing grade of tumor was observed. Furthermore, greater Ki67 positivity was found in cases with lymph node metastasis and distant metastasis. Future studies with a larger number of patients will be required to precisely define the correlation of Her2/neu expression and Ki67 positivity with clinicopathological parameters. The results however are encouraging and suggest evaluation of Her2/neu as a candidate for targeted therapy.

• Korean Journal of Bronchoesophagology
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• v.16 no.1
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• pp.39-46
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• 2010

Background and Objectives Various tumor markers have been studied in an attempt to evaluate and decide the optimal treatment of the patients with head and neek squamous cell carcinoma (HNSCC). A nuclear antigen Ki-67 is a proliferative marker of tumor cells in all phases of cell cycle except G0. c-met gene, the tyrosine kinase receptor for hepatocyte growth tactor, may play various roles in malignant transformation. The authors evaluated the prognostic significance of Ki-67 and c-Met in surgical specimens of HNSCC to determine the relationship with the various clinicopathological characteristics. Materials and Methods Formatin-fixed paraffin-embedded surgical specimens were obtained from 54 patients with HNSCC. Ki-67 and c-Met expressions were analyzed by immunohistochemical staning and were compared with the clinicopathological characteristics such as, pathologic differentiation, tumor stage, clinical stage and lymph node metastasis. Results Ki-67 and c-Met over-expression was detected in 66.7% and 90.7% in HNSCC. There was positive correlation of increased expression of Ki-67 with tumor stage. and clinical stage, increased expression of e-Met with tumor stage, clinical stage, and nodal status. The expression of c-Met had a significant positive relationship with Ki-67 index (p<0.05). Conclusion Therefore, Ki-67 and c-Met are useful markers of tumor progression, aggressiveness and prognosis in HNSCC.