Exon 11 mutations, Ki67, and p16INK4A as predictors of prognosis in patients with GIST

Cerski, Marcelle Reesink; Pereira, Fernanda dos Santos; Matte, Úrsula; Oliveira, Francine Hehn de; Crusius, Felipe L.; Waengertner, Luiz Eduardo; Osvaldt, Alessandro Bersch; Fornari, Fernando; Meurer, Luíse

doi:10.1016/j.prp.2011.09.008

Cited by 16 publications

(8 citation statements)

References 50 publications

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“…In documented research, different cut-off points have been suggested: 0.82% [25], 2.7% [26], 3% [27], 5% [15,23], 6% [28], or 10% [29]; however few of these cut-off points were established based on ROC analysis. In our series, a 1% LI was confirmed as the best threshold value for relapse in ROC analysis, with 71.7% sensitivity and 64.5% specificity.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of gastrointestinal bleeding and expression of PTEN and Ki-67 on primary gastrointestinal stromal tumors

et al. 2014

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BackgroundPrognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation. The latest risk classification criteria may still have room for improvement. This study aims to investigate prognostic factors for primary GISTs from three aspects, including clinicopathological parameters, immunohistochemical (IHC) expression of PTEN, and Ki-67 labeling index (LI), and attempts to find valuable predictors for the malignancy potential of primary GISTs.MethodsTumor samples and clinicopathological data from 84 patients with primary GISTs after R0 resection were obtained. Immunohistochemical analysis was performed based on tissue microarray (TMA) to estimate expression of PTEN and Ki-67 in tumor cells.ResultsThe cut-off point of Ki-67 LI was determined as 1%, using a receiver operator characteristic test with a sensitivity of 71.7% and a specificity of 64.5%. Univariate analysis demonstrated the following factors as poor prognostic indicators for relapse-free survival (RFS) against a median follow-up of 40.25 months: gastrointestinal (GI) bleeding (P = 0.009), non-gastric tumor location (P = 0.001), large tumor size (P = 0.022), high mitotic index (P < 0.001), high cellularity (P = 0.012), tumor rupture (P = 0.013), absent or low expression of PTEN (P = 0.036), and Ki-67 LI >1% (P = 0.043). Gastrointestinal bleeding (hazard ratio, 3.85; 95% confidence interval, 1.63 to 9.10; P = 0.002) was a negative independent risk predictor in multivariate analysis, in addition to tumor size (P = 0.023), and mitotic index (P = 0.002). In addition, GI bleeding showed a good ability to predict recurrence potential, when included in our re-modified risk stratification criteria.ConclusionsThis study suggests that GI bleeding is an independent predictor of poor prognosis for RFS in primary GISTs. Expression of PTEN and Ki-67 are correlated with high risk potential and may predict early recurrence in univariate analysis.

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Section: Discussionmentioning

confidence: 99%

Prognostic impact of gastrointestinal bleeding and expression of PTEN and Ki-67 on primary gastrointestinal stromal tumors

et al. 2014

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“…A scoring index was then calculated by multiplying staining intensity by the percentage of positively stained cells [21]. In previous studies, the cut-off point of continuous variables was determined by receiver–operator characteristic (ROC), using recurrence as a basis [22]. However, the postoperative recurrence time varied dramatically in the present study (4 to 108 months), which may reflect differences in the biological behavior of the tumors.…”

Section: Methodsmentioning

confidence: 82%

“…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%

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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“…It has been shown that abnormal expression of p16 is associated with several cancers, such as lung, laryngeal, and tonsillary carcinomas [29][30][31]. Various scoring methods have been used in studies comparing p16 expression and prognostic parameters in various neoplasms [32][33][34]. In bladder cancer, there is no consensus about the regarding the p16 staining pattern.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of different p16 immunostaining methods and the prognostic role of p16/Ki-67 combined expression in non-muscle invasive bladder cancers

Özyalvaçlı¹,

Özyalvaçlı²,

Astarci³

et al. 2015

pjp

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Exon 11 mutations, Ki67, and p16INK4A as predictors of prognosis in patients with GIST

Cited by 16 publications

References 50 publications

Prognostic impact of gastrointestinal bleeding and expression of PTEN and Ki-67 on primary gastrointestinal stromal tumors

Prognostic impact of gastrointestinal bleeding and expression of PTEN and Ki-67 on primary gastrointestinal stromal tumors

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

Evaluation of different p16 immunostaining methods and the prognostic role of p16/Ki-67 combined expression in non-muscle invasive bladder cancers

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