Ki-67 expression score correlates to survival rate in gastrointestinal stromal tumors (GIST)

Neto, Ricardo Artigiani; Logullo, Ângela Flávia; Stávale, João Norberto; Lourenço, Laércio Gomes

doi:10.1590/s0102-86502012000500007

Cited by 21 publications

(8 citation statements)

References 37 publications

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“…For example, Ki67, a nuclear protein associated with cellular proliferation, has been associated with poor outcomes in GIST patients [9], [23], [24], while others have reported contradictory or inconclusive findings with Ki67 labeling [27], [28]. Our results showed that high nuclei Ki67expression correlated with necrosis and high mitotic index, which also reflect cellular proliferation.…”

Section: Discussionsupporting

confidence: 45%

“…Based on both the data features and the ROC curve, p53 was classified into 2 categories, index <10 and index ≥10, and p27 was classified into 3 categories, index <100, index between 100–200, and index >200. Although, different cut-off points for Ki67 have been described, varying from 0.82% to 10%, 3% and 5% have been the cut-offs used most often for GISTs [22], [23]. Here, a 5% cut-off was found to be better than 3% to classify cases using Kaplan-Meier curves.…”

Section: Methodsmentioning

confidence: 87%

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SKP2 High Expression, KIT Exon 11 Deletions, and Gastrointestinal Bleeding as Predictors of Poor Prognosis in Primary Gastrointestinal Stromal Tumors

Tian

et al. 2013

PLoS ONE

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Background and AimsConsidering the indication of adjuvant therapy, the recurrence risk for primary gastrointestinal stromal tumor (GIST) after surgery needs to be accurately estimated. However, current risk stratification schemes may still have room for improvement. This study seeks to analyze prognostic factors for primary GISTs from 3 aspects, including clinicopathological parameters, immunohistochemical biomarkers, and gene mutational status, and attempts to find novel valuable factors predicting the malignancy potential of GISTs.MethodsRetrospective data from 114 primary GIST patients after R0 resection were collected. Clinicopathological data was obtained from medical records and re-evaluated. Immunohistochemical analysis was performed using the Tissue Microarray method for Ki67, p16, p27, p53, SKP2, CD133, and actin. KIT gene exons 9, 11, 13, and 17 and PDGFRα gene exons 12 and 18 were tested for mutations using PCR.ResultsUnivariate analysis revealed the following factors as poor prognostic indicators for relapse-free survival with a median follow-up of 50 months: male gender, gastrointestinal bleeding, mitotic index >5/50HPFs, tumor size >5 cm, non-gastric site, necrosis, epithelioid or mixed cell type, surrounding tissue invasion, Ki67>5%, p16>20%, p53 index >10, SKP2>10%, and KIT exon 11 deletion. Besides mitotic index, tumor size and site, SKP2 high expression (RR = 2.91, 95% CI: 1.41–5.99, P = 0.004) and KIT exon 11 deletion (RR = 2.73, 95% CI: 1.04–7.16, P = 0.041) were also independent risk factors in multivariate analysis, with gastrointestinal bleeding also showing a trend towards significance (RR = 1.88, 95% CI: 0.98–3.64, P = 0.059). In addition, gastrointestinal bleeding and SKP2 high expression showed a good ability to stratify high-risk patients further.ConclusionOur results show that gastrointestinal bleeding, SKP2 high expression, and KIT exon 11 deletions may be useful indicators of high recurrence risk for primary GIST patients.

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Section: Discussionsupporting

confidence: 45%

Section: Methodsmentioning

confidence: 87%

SKP2 High Expression, KIT Exon 11 Deletions, and Gastrointestinal Bleeding as Predictors of Poor Prognosis in Primary Gastrointestinal Stromal Tumors

Tian

et al. 2013

PLoS ONE

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“…[ 40 ] Current publications also suggest that a high Ki67 index may indicate metastasis and recurrence. [ 41 , 42 ] Wong et al found that Ki67 was less reliable than the mitotic count, although it proved useful in assessing the proliferation rate of the tumor cells in GIST. [ 43 ] The study suggested that the 1-, 3-, and 5-year survival rates of the Ki67 + GIST group were lower than those of the Ki67 group.…”

Section: Discussionmentioning

confidence: 99%

Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors

Zhou

Chen

et al. 2017

Medicine

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Background:Ki67 is a good marker of cell proliferation in a variety of tumors. High ki67 levels are usually associated with poor prognosis. However, the relationship between Ki67 expression and the risk of malignancy of gastrointestinal stromal tumors (GISTs) is still poorly defined. The current meta-analysis was initiated to address this issue.Methods:Studies reporting Ki67 expression and the risk of malignancy in GIST were found by searching Cochrane Library, PubMed, Medline, and Embase until October 31, 2016. A total of 9 studies involving 982 patients were included. Pooled odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated using a fixed-effect model.Results:Meta-analysis showed no significant difference in the incidence of Ki67 overexpression between the very low NIH group and the low NIH group (OR: 0.66, 95% CI: 0.25–1.76; P = .41, Pheterogeneity = .25). However, the incidence of Ki67 overexpression gradually increased from the low NIH group to the high NIH group (OR: 0.46, 95% CI: 0.27–0.80; P = .005, Pheterogeneity = .13) and (OR: 0.22, 95% CI: 0.15–0.34; P < .00001, Pheterogeneity = .33).Conclusions:There were more GIST patients with Ki67 overexpression in the intermediate and high NIH groups than in the low NIH group. Ki67 overexpression may be a useful marker of the risk of malignant GIST transformation.

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“…Certain studies have demonstrated that Ki-67 + expression is closely associated with the aggressive biological behavior of tumor cells in GISTs (17). The marker represents a good prognostic predictor for GISTs (30). However, the significance of Ki-67 in predicting the prognosis of GISTs remains in dispute.…”

Section: Discussionmentioning

confidence: 99%

CD133 and Ki-67 expression is associated with gastrointestinal stromal tumor prognosis

Liu

et al. 2013

Oncology Letters

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CD133+ tumor cells have a greater potential ability for tumorigenesis, proliferation, invasion and metastasis compared with CD133− tumor cells. Ki-67 is associated with cell proliferation in various tumors and has a markedly positive correlation with the prognosis of patients. However, there are a limited number of studies that have investigated the association between the prognosis of gastrointestinal stromal tumors (GISTs) and the two markers. The present study aimed to investigate CD133 and Ki-67 expression in GISTs and to explore their clinicopathological significance in the prognosis of patients with GISTs. A total of 111 GIST patients from the Chinese People’s Liberation Army (PLA) General Hospital were retrospectively followed up and immunohistochemistry was used to detect CD133, Ki-67 and CD117 expression in the tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. The log-rank test, χ2 test and Cox’s proportional hazards model were used to determine the association between CD133, Ki-67, CD117 expression and the prognosis of GIST. The 1-, 3- and 5-year survival rates were 93.0, 89.0 and 82.0%, respectively, in all the patients. However, in the patients with CD133+ or Ki-67+, the 1-, 3- and 5-year survival rates were 81.0, 61.5 and 50.0% and 83.0, 66.6 and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were statistically lower (CD133 log-rank, P=0.028; Ki-67 log-rank, P=0.002). The multivariate Cox analysis revealed that CD133 and Ki-67 expression were considerable factors in the prognosis of GIST patients (CD117, P=0.495; CD133, P=0.036; Ki-67, P=0.003). In conclusion, the positive expression of CD133 and Ki-67 was associated with a poor prognosis of GIST.

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Ki-67 expression score correlates to survival rate in gastrointestinal stromal tumors (GIST)

Cited by 21 publications

References 37 publications

SKP2 High Expression, KIT Exon 11 Deletions, and Gastrointestinal Bleeding as Predictors of Poor Prognosis in Primary Gastrointestinal Stromal Tumors

SKP2 High Expression, KIT Exon 11 Deletions, and Gastrointestinal Bleeding as Predictors of Poor Prognosis in Primary Gastrointestinal Stromal Tumors

Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors

CD133 and Ki-67 expression is associated with gastrointestinal stromal tumor prognosis

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