• Title, Summary, Keyword: Ki-67

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Assessment of Ki-67 for Predicting Effective Prognosis in Breast Cancer Subtypes

  • Park, Sangjung;Park, Sunyoung;Kim, Jungho;Ahn, Sungwoo;Park, Kwang Hwa;Lee, Hyeyoung
    • Biomedical Science Letters
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    • v.24 no.1
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    • pp.9-14
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    • 2018
  • Ki-67 has been widely performed and become an important biomarker in worldwide clinics, but the standard cut off value of Ki-67 index in breast cancer is still controversy. The objective study was to understand the Ki-67 in breast cancer subtypes and to investigate relative risk of breast cancer subtypes according to Ki-67 cut off value in Korean breast cancer. Immunohistochemical staining (IHC) for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 index was examined from 123 breast cancer patients. Ki-67 index was significantly overexpressed in PR, ER, and HER2 hormone negative groups. Ki-67 index in Triple negative and HER2 subtypes was shown significantly higher than that in Luminal A and Luminal B subtype. Then, we compared the relative risk of each subtype according to 14% and 20% Ki-67 cut off value, which were applied in most clinics. Especially, 20% Ki-67 cut off value in HER2 and Triple negative subtypes was shown 8.41 fold and 2.83 fold higher relative risk than this in Luminal A subtype. Moreover, Ki-67 index in HER2 2+ or 3+ status showed significantly overexpressed than this in HER2 1+ status. At the 20% Ki-67 cut off value, HER2 1+ or 2+ status and 3+ status showed significant difference. Therefore, the 20% Ki-67 cut off value will be useful as a precise prognostic management and helpful for interpreting diverse outcomes of other subtypes in breast cancer patients.

Ki-67 Can Predict the Response to the Gemcitabine, Oxaliplatin And L-asparaginase Regimen (GELOX) and Prognosis in Patients with Nasal Natural Killer/T-cell Lymphoma

  • Zhang, Jing;Jiang, Wei;Wang, Wei-Da;Liu, Cheng-Cheng;Hu, Yan-Ping;Xia, Zhong-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4515-4520
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    • 2015
  • GELOX (gemcitabine, oxaliplatin and L-asparaginase) regimen showed an impressive result in our previous study, but the effect of this new regimen is still dissatisfying for some patients, so it is necessary to identify which patients will benefit from this regimen. A total of fifty-one cases with nasal natural killer/T-cell lymphoma receiving initial GELOX chemotherapy were enrolled in this study. The ki-67 expression detected by immunohistochemistry (IHC) in the specimens ranged from 10% to 90%, with a median value of 70%, so cases higher than the median value (${\geq}70%$) were defined as high ki-67 expression, and the others were designated as low ki-67 expression. The response rate had no statistical difference between low ki-67 expression group and high ki-67 expression group (P=0.291) though the value in the former group was relatively high. After a median follow-up of 18.03 months, the 3-year progression-free survival (PFS) for patients with low ki-67 expression was significantly higher than those with high ki-67 expression (83.8% vs. 47.9%, P=0.038). In the stage I/II subgroup, 3-year PFS and overall survival (OS) were statistically higher in the patients with low ki-67 expression than those with high ki-67 expression. Multivariate analysis revealed high ki-67 expression was an independent prognostic factor for PFS. These results suggest that low ki-67 expression can predict a good response of GELOX in these patients, and the combination of ki-67 expression and early stage is helpful to identify an excellent prognosis subgroup from patients receiving GELOX in this disease.

Clinical Significance of Increased Ki-67 Protein Expression in Non-small Cell Lung Cancers (비소세포폐암 환자에시 Ki-67 단백질 발현증가의 임상적 의의)

  • Lee Gun;Lim Chang-Young;Kim Kwang-Il;Lee Hyeon-Jae
    • The Korean Journal of Thoracic and Cardiovascular Surgery
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    • v.39 no.5
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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.

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

  • Kilickap, Saadettin;Kaya, Yalcin;Yucel, Birsen;Tuncer, Ersin;Babacan, Nalan Akgul;Elagoz, Sahande
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1381-1385
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    • 2014
  • Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of this study was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2 and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathological features of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163 patients with breast cancer were analyzed, with a mean age of $53.4{\pm}12.2$ years. Median Ki67 positivity was 20% and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001), estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymph node positivity (p<0.003). Lower Ki67 levels were significantly associated with longer median relapse-free and overall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated with ER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The level of Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.

Expression of the p16 and Ki67 in Cervical Squamous Intraepithelial Lesions and Cancer

  • Kanthiya, Kanjana;Khunnarong, Jakkapan;Tangjitgamol, Siriwan;Puripat, Napaporn;Tanvanich, Sujitra
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3201-3206
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    • 2016
  • Purpose: To evaluate the expression of p16 and Ki67 in cervical intraepithelial neoplasia (CIN) and cancer. Materials and Methods: We performed a immunohistochemical study of p16 and Ki67 in 243 cervical tissues - 53 non-dysplastic lesions, 106 CIN1, 61 CIN2/3 and 23 squamous cell carcinomas. The expression of p16 and Ki67 was interpreted independently by 2 researchers and the sensitivity and specificity to detect clinically significant lesions (${\geq}CIN2$) were determined. Results: The overall agreement results of positive or negative immunostaining of intra-inter observer variability were 0.659 for p16 and 0.808 for Ki67. p16 expression was demonstrated in 91.3% of invasive carcinomas, 78.7% of CIN2/3, 10.4% of CIN1 and 9.4% of non-dysplasic lesions. The corresponding Ki67 expression was: 100% of all invasive carcinomas, 75.4% of CIN2/3, 22.6% of CIN1, and 11.3% with non-dysplasia. The expression was significantly different between CIN2/3 vs CIN1 for both p16 and Ki67 (p-values <0.001 both), and cancer vs CIN2/3 for Ki67 (p-value 0.008). The differences were not significant between CIN1 vs non-dysplasia (p-values 1.000 for p16 and 0.130 of Ki67), and cancer vs CIN2/3 for p16 (p value 0.219). The sensitivity and specificity to detect > CIN2 were 84.5% and 90.5% by p16 and 82.1% and 88.6% by Ki67. Conclusions: The rates for 16 and Ki67 expression were directly associated with the severity of cervical lesions. Significant differences in these markers expression may be useful in cases with equivocal histologic features among cervical intraepithelial lesions, but not between CIN1 and non-dysplastic lesions. The two markers had high sensitivity and specificity in determining >CIN2.

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

  • Haroon, Saroona;Hashmi, Atif Ali;Khurshid, Amna;Kanpurwala, Muhammad Adnan;Mujtuba, Shafaq;Malik, Babar;Faridi, Naveen
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4353-4358
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    • 2013
  • Introduction: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, which can be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO do not recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We therefore aimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymph node metastasis, ER, PR and HER2neu status. Methods: A total of 194 cases of newly diagnosed breast cancer were included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed by the DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated both as continuous and categorical variables. Results: Mean age of the patients was 51.7 years (24-90). Mean Ki67 index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%) and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade, PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size. There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen with HER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as compared to intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. Conclusion: Our study indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognostic markers because we found that tumors with Ki67 higher than 30% have better prognostic profile compared to tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis and HER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate and low groups when considering adjuvant chemotherapy and prognostic stratification.

CORRELATION BETWEEN P53, PCNA AND KI-67 EXPRESSION IN HEAD NECK SQUAMOUS CELL CARCINOMA (두경부 편평상피세포암의 p53단백과 PCNA 및 Ki-67의 발현양상)

  • Lee, Eun-Jin;Lee, Sang-Han;Sohn, Yoon-Kyung
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.2
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    • pp.142-149
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    • 2001
  • To investigate the correlation between the clinical features and the expression of p53, PCNA, and Ki-67 of the head neck squamous cell carcinoma, immunohistochemicalstaining of p53, PCNA, and Ki-67 on the paraffin embedded tissue blocks of 116 surgically removed specimens were done. The staining intensity was divided as grade 1 to grade 3 and the results were statistically analysed. 1. The positive reation rates of cell proliferation markers (PCNA and Ki-67) were higher than that of p53. There was significant correlations of the PCNA and Ki-67 expression but there was no significant correlations between p53 and PCNA or p53 and Ki-67. 2. There were no significant correlation between the expression of p53, PCNA and Ki-67 and tumor site or tumor size. 3. There was no significant differences in the positive response according to the nodal status. The node metastasis groups revealed that higher proportion of grade 3 staining of PCNA and Ki-67 than node negative group. From the above results it is concluded that p53 and cell proliferation markers PCNA and Ki-67 might have their unique mechanism involving in the growing and progression of tumor. Overexpression of p53 does not appear to represent an independent prognostic marker in head neck squamous cell carcinoma.

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Expression of Human Epidermal Growth Factor Receptor (Her 2/neu) and Proliferative Marker Ki-67: Association with Clinicopathological Parameters in Gallbladder Carcinoma

  • Pujani, Mukta;Makker, Isha;Makker, Annu;Goel, Madhu Mati;Jetley, Sujata
    • 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.

Ki-67 is a Valuable Prognostic Factor in Gliomas: Evidence from a Systematic Review and Meta-analysis

  • Chen, Wen-Jie;He, De-Shen;Tang, Rui-Xue;Ren, Fang-Hui;Chen, Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.411-420
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    • 2015
  • Ki-67 has been widely used as an indicator of cell proliferation in gliomas. However, the role of Ki-67 as a prognostic marker is still undefined. Thus, we conducted a meta-analysis of the published literatures in order to clarify the impact of Ki-67 on survival in glioma cases. Eligible studies were identified in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, Science Direct and Wiley Online Library with the last search updated on August 31, 2014. The clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with Ki-67 expression at different time points were extracted. A total of 51 studies, covering 4,307 patients, were included in the current meta-analysis. The results showed that overexpression of Ki-67 can predict poor OS (HR=1.66, 95%CI: 1.53-1.80; Z=11.87; p=0.000) and poor PFS (HR=1.67, 95%CI: 1.47-1.91; Z=7.67; p=0.000) in gliomas. Moreover, subgroup analyses also indicated that high level of Ki-67 expression was related to poor OS and PFS in glioma patients regardless of region, pathology type, cut-off value and statistical method. In conclusion, the current meta-analysis revealed that Ki-67 expression might be a predicative factor for poor prognosis of glioma patients, emphasizing its importance as a predictor.

The Significance of c-Met and Ki-67 Expression in the Head and Neck Squamous Cell Carcinoma (두경부 편평세포암에서 c-Met 단백과 Ki-67 발현의 의의)

  • Kim, Jun;Do, Nam-Yong;Park, Jun-Hee;Choi, Ji-Yun;Lim, Sung-Chul
    • 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.

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