• Journal of Chest Surgery
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• 제39권5호
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• pp.376-381
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• 2006

배경: Ki-67 단백질은 세포의 증식활성도를 나타내는 생물표식자로, 비소세포폐암 환자에서 Ki-67 단백질의 증가는 예후에 나쁜 영향을 미치는 것으로 알려져 있다. 이 연구는 비소세포폐암으로 폐절제술을 실시한 환자에서 Ki-67 단백질의 발현정도를 조사하여, 단백질의 발현증가가 환자의 임상적 병리적 양상과 술 후 재발과 생존기간에 미치는 영향을 알아보기 위해 시행되었다. 대상 및 방법: 근치적 폐절제술을 실시한 38명의 비소세포폐암 조직에서 단클론항체 Ki-67로 면역조직화학염색을 실시하여 Ki-67 Labeling Index (LI)를 구하였다. 환자를 Ki-67 증가군$(LI{\ge}20%)$과 Ki-67 비증가군(LI<20%)으로 분류하여, 두 군의 술 전 임상적 병리적 특성, 술 후 생존기간 및 무병생존기간을 비교하였다. 결과: Ki-67 LI는 불균질한 분포를 보였고 평균 LI는 $20.0{\pm}20.1%$였다. Ki-67 증가군과 비증가군 간에나이, 성별, 흡연, TNM 병기, 혈관침윤은 유의한 차이가 없었다. 그러나 증가군은 비증가군에 비해 편평상피암이 많고, 분화도가 나쁘며, 임파침윤이 많았다$(p{\le}0.05)$. 증가군은 중앙 생존기간(47.2 vs. 96.5개월)과 중앙 무병생존기간(18.2 vs. 72.3개월)이 비증가군보다 짧았으나 통계적 유의성은 없었다(각각 p=0.312, p=0.327). 결론: 이상의 연구를 통해 비소세로폐암 환자에서의 Ki-67 단백질 발현증가는 수술 후 환자의 예후에 나쁜 인자로 작용하여 생존기간과 무병생존기간이 짧아지는 경향을 보였으나 통계적 유의성이 부족하여 향후 지속적인 연구가 필요할 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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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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• 제20권1호
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• pp.73-80
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• 2002

목적 : 종양의 성장은 세포의 증식과 소실의 순수한 결과이며, 대부분의 종양들에서 아포프토시스는 계속되는 세포 소실의 가장 중요한 부분을 차지하고 있다. 본 연구에서는 비호지킨림프종 환자들을 REAL 분류에 따라 재분류한 다음 면역조직화학 염색을 이용하여 아포프토시스 지수, Ki-67 세포증식지수, Bcl-2 단백 발현, P53 단백 발현을 관찰하여 종양의 성장에 영향을 주는 여러 인자들의 관련 양상을 알아보고자 하였다. 대상 및 방법 : 비호지킨림프종 환자 67명을 대상으로 하였다. Working Formulation을 이용하여 분류하였을 때 저등급이 3명, 중등급이 64명이었다. 세포 표현형은 전체 67명의 환자 중 47명$(70\%)$이 B세포 표현형이었고, 18명$(27\%)$이 T세포 표현형이었으며, 2명에서는 분류할 수 없었다. 환자의 파라핀 포매 조직을 이용하여 면역조직화학 염색을 실시하여 아포프토시스 지수와 Ki-67 세포증식지수, Bcl-2 단백발현, P53 단백발현을 관찰하였다. 결과 : Bcl-2 단백의 발현은 $40\%$ (26/65)에서 양성 반응을 보였다. P53 단백의 발현은 $31\%$ (20/65)에서 보였다. 아포프토시스 지수는 $0\%$와 $15\%$사이의 범위에 있었으며 평균은 2.16이고 중앙값은 1.2이었다. 아포프토시스 지수는 세포 표현형이나 P53 단백발현 여부에 따라 의미 있는 차이를 보이지 않았으나, Bcl-2 단백발현 여부에 따라서는 통계학적으로 의미 있는 차이를 보였다(p=0.005). Bcl-2 단백발현이 양성이면 아포프토시스 지수가 낮았다. Ki-67 세포증식지수는 $1\%$와 $91\%$ 사이의 범위에 있었으며 평균은 $55.4\%$이었다. Ki-67 세포증식지수는 세포표현형이나 B치-2 단백발현 여부에 따라 의미 있는 차이를 보이지 않았으나, P53 단백발현 여부에 따라서는 통계학적으로 의미있는 차이를 보였다(p=0.000). 전체 환자군에서는 아포프토시스 지수와 Ki-67 세포증식지수 사이에 관련이 없었으나, Bcl-2 단백발현 양성인 환자에서는 아포프토시스 지수가 증가하면 Ki-67 세포증식지수가 증가하는 경향이 있었다(p=0.012). 결론 : Bcl-2 단백발현이 양성이면 아포프토시스 지수가 낮았고, P53 단백발현이 양성이면 Ki-67 세포증식지수는 높았다. 또한 Bcl-2 양성인 환자에서는 아포프토시스 지수와 Ki-67 세포증식지수사이의 양성 연관성을 보였는데 이는 아포프토시스가 종양의 성장에 있어서 세포의 증식과 별도로 분리하여 생각할 수 없는 것임을 시사해준다고 본다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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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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• 제38권12호
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• pp.835-843
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• 2005

배경: 분자학적 표지자들과 식도암과의 관련성에 대해서 아직 뚜렷하게 밝혀진 바가 없다. 본 연구에서는 먼저 p53, Cyclin D1과 Ki67 지수 등 종양 표식자가 국내 식도암 환자에서 수술 후 얻어진 식도암 조직의 병기, 악성도, 임파선 전이 여부 등과 어떠한 관련성이 있는가를 알아보고 이를 이용해 향후 국내 식도암 환자에 대한 예후 분석 및 치료방침 결정 그리고 조기발견에 이용할 수 있는지 알아보았다. 또한 본 연구는 분자학적 표지자들의 임상적용의 기초를 마련하고자 하는 목적으로 시행하였다. 대상 및 방법: 1992년 3월부터 수술 후 조직절편이 보존된 124명의 환자를 대상으로 하였다. 조직절편의 파라핀을 제거한 뒤에 p53 변이, Cyclin D1의 과발현, Ki67 지수에 대한 면역조직화학 염색법을 시행하였으며 조직슬라이드상에서 세포분열지수를 구하였다. 이 결과와 임상적인 변수들과의 상관관계를 분석하였고, 환자의 생존 및 재발 결과와 비교하였다. 결과: 환자의 성별, 나이, 병기, 종양 크기, 타장기 전이 여부, 국소적인 재발 여부와 p53의 변이, Cyclin D1의 과발현, Ki67 지수, 세포분열 지수에 따른 통계적으로 유의한 차이는 없었다. Ki67 지수는 40 미만인 경우와 40 이상인 경우로 나누었을 경우 통계적으로 유의하게 생존기간에 있어서 차이가 나는 것으로 나타났으나(p=0.011) 다른 표지자들은 생존기간에 유의한 차이를 보이지 않았다. 결론: 높은 Ki67지수는 식도의 편평상피암의 예후에 나쁜 영향을 미치는 것으로 나타났으나 다른 표지자들은 영향을 미치지 않았다 이번의 연구를 통해 분자학적인 지표들이 임상적으로 가치 있는 인자가 될 수 있다고 판단되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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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.

• 대한임상검사과학회지
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• 제36권2호
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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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• 제13권5호
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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.

• 대한임상검사과학회지
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• 제39권3호
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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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• 제15권12호
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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.