• 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.

• 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.

• 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.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.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.104-109
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• 1998

Purpose : The proliferative nuclear antigen Ki-67, present in all cell cycle phases except G0, is a useful marker for the detection of proliferative cells in vivo. MIB I has been found to recognize an antigen in formalin-fixed and wax-embedded material. The aim of this study was to assess the efficacy of MIB-1 expression as a marker of representing the status of mesangial cell proliferation in renal tissues. Methods : Immunohistochemical staining for Ki-67 Ag using monoclonal antibody MIB-1 (Immunotech,505) were performed in 41 renal tissuses which were obtained by percutaneous renal biopsy done between January 1994 and December 1996. Results : In both glomeruli and renal tubules, MIB-1 expression was observed only in 2 of 18 ($11.1\%$) cases of IgA nephropathy, in 2 of the 4 ($50\%$) cases of mebranoproliferative glomerulonephritis, in 4 of the 5 ($80\%$) cases of poststreptococcal glomerulonephritis. But MIB-1 expression was not detected in all cases of minimal lesion and membranous nephropathy. Renal tubules In another 7 cases of IgA nephropathy were MIB-1 positive. Conclusion : MIB-1 expression in renal tissues may relate to the cell proliferation in glomeruli and renal tubules. But the efficacy of MIB-1 expression as a marker of mesangial cell proliferation may reveal a limited value because of it's lower positive rate in IgA nephropathy.

• 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.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.

• Imaging Science in Dentistry
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• v.34 no.2
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• pp.75-79
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• 2004

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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3595-3600
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• 2016

Background: To investigate the association between preoperative pathological Ki-67 labeling index and serum tumor marker cancer antigen 15-3 (CA 15-3) with clinic-pathological parameters and treatment outcomes in early breast cancer. Materials and Methods: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 6-8 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). Results: A total of 280 pts was included. The median age was 49 years (38-66 y) and median overall survival was 35 (20-38) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki-67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki-67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki-67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki-67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. Conclusions:Preoperative Ki-67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.11-17
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• 2002

Objectives: Expression of HMGI(Y), a nucleoprotein that binds to A/T rich sequences in the minor groove of the DNA helix, is observed in neoplastically transformed cells but not in normal cells. We have analyzed HMGI(Y), p53 expression and Ki-67 labelling index in squamous cell carcinomas of the head and neck, and evaluated its clinicopathologic significance. Materials and Methods: 40 cases of squamous cell carcinoma of the head and neck were entered on the study of immunohistochemical stains for HMGI(Y), p53 and Ki-67. We analyzed the relationship between HMGI(Y), p53, Ki-67 expression and age, sex, primary tumor site, stage, survival rate, recurrence. Results: HMGI(Y) expression evidenced by immunohistochemical staining was observed in 35 of 40 (87.5%) squamous cell carcinoma of the head and neck. But no significant correlation was observed between HMGI(Y) expression and other clinical factors such as primary site, tumor stage, differenciation, cervical lymph node, metastasis, recurrence and immunohistochemical status of p53. The Ki-67 labelling index was significantly correlated with recurrence and HMGI(Y) expression (p<0.05). Conclusion: This results suggest the Ki-67 is a good prognostic factor and the HMGI(Y) expression plays some roles in carcinogenesis and cellular proliferation of squamous cell carcinoma of the head and neck. HMGI(Y) gene can be used as a cancer marker, the correlation between the gene expression and the prognosis of the cancer patient should be proved in the future studies.