Prognostic significance of expressions of cell-cycle regulatory proteins in gastrointestinal stromal tumor and the relevance of the risk grade

Nakamura, Norimoto; Yamamoto, Hidetaka; Yao, Takashi; Nishiyama, Ken Ichi; Imamura, Masakazu; Yamada, Tomomi; Nawata, Hajime; Tsuneyoshi, Masazumi

doi:10.1016/j.humpath.2005.03.012

Cited by 123 publications

(135 citation statements)

References 33 publications

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“…The expression of Ki67 changes widely from one study to another, probably by the variety of the cut-offs accepted by each author. We accepted the cut-off of 10% as described by TOQUET et al (34) and NAKAMURA et al (30) .These authors have defined the mean level as the cut-off of the GISTs tumors studied (4.92) and MEARA et al (24) as 5%. In this research the median of the Ki67LI obtained was 9.57 and the mean value was 12.34.…”

Section: Discussionmentioning

confidence: 99%

“…The sections were judged positive for p53 when 5% or more of the nucleus of tumor cells were stained as described by MEARA et al (24) and NAKAMURA et al (30) . Ki67 labelling index was determined by observing 1000 nuclei in areas of the section with the highest labelling rates, and was considered positive when 10% or more of tumor cells were stained.…”

Section: Imunohistochemistrymentioning

confidence: 99%

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Ki67 and p53 in gastrointestinal stromal tumors - GIST

Neves¹,

Oshima²,

Neto³

et al. 2009

Arq. Gastroenterol.

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-Context -Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor. Cellular proliferation and apoptosis is gaining importance for predicting prognosis in several cancers. Objective -To investigate the Ki67 and p53 immunostaining in GISTs. Methods -Specimens from 40 patients with GIST were assessed for immunohistochemical expression of Ki67 and p53. The tumors were divided according the risk of recurrence in two groups: I with high or intermediate risk and; II with low or very low risk. Results -Among the 40 patients, 21 were men, the mean age was 56 years, 16 occurred in the small intestine and 13 in the stomach, 5 in the retroperitonium, 4 in the colon or rectum and 2 in the mesenterium. Thirty two tumors were from group I and 8 from group II. Half of the patients developed recurrence, being 90% of the group I (P = 0.114). The tumor Ki67 labelling index ranged from 0.02 to 0.35 (mean level 0.12). This index was marginally higher in the group I patients with recurrence (P = 0.09) compared to the patients of the same group without recurrence. p53 staining was expressed in 65% of the GISTs. A higher frequency of p53 and Ki67 had been found in the group I tumors when compared to the other group (P = 0.022; OR = 8.00 -IC 95%: 1.32-48.65). Conclusion -The most common site was the small intestine and 80% had a malignant potential justifying the high recurrence observed. No significant correlation was found between p53 and overall outcome of the patients. In group I patients, the evaluation Ki67LI may be a marker of prognosis. The positivity of both markers is higher among the patients with worst prognosis than in the others. HEADINGS -Gastrointestinal stromal tumors. Ki-67 antigen. Tumor suppressor protein p53.

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Section: Discussionmentioning

confidence: 99%

Section: Imunohistochemistrymentioning

confidence: 99%

Ki67 and p53 in gastrointestinal stromal tumors - GIST

Neves¹,

Oshima²,

Neto³

et al. 2009

Arq. Gastroenterol.

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“…In GIST, Ki-67 expression has been previously associated to morphological variables and also survival, but results are hardly comparable due to methodological different approach 19,20,23,31 .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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PURPOSE: To evaluate the immunohistochemical expression of p16, Ki-67, p53 and Bcl-2 proteins in gastrointestinal stromal tumors (GIST); to assess the possible association between these variables and clinical and histopathological factors of cancer; and to check for prognostic value of these variables (survival and recurrence). METHODS: A sample of 55 patients treated surgically for GIST in three hospitals was studied. The surgically excised tumors were confirmed as GIST by KIT, vimentin, desmin S100 protein, CD117, 1A4 and CD34 assessment in paraffin blocks. RESULTS: Only 9 (16%) cases of GIST were positive for p53, p16 was positive among 43.6%; 80% of GISTs showed staining for Bcl-2. The proliferative index (expressed as the proportion of positive cells) assessed by immunohistochemical expression of Ki-67 was high in 49% of cases. Elevated Ki-67 scores were associated to high histological grade (p=0.0026) and mitosis index, MI (p=0.0001). High Ki-67 index was associated to death. Expression of p53, p16 and Bcl-2 did not correlate to morphological or clinical variables. CONCLUSIONS: Ki-67 immunohistochemical evaluation should be included in preoperative evaluation of GIST biopsies or surgical specimens as a prognostic tool for clinical staging; and all other proteins studied (Bcl-2, p53 and p16) did not play a role in GIST metabolic or carcinogenic process, remaining without prognostic value.

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“…Previous studies have reported the prognostic significance of tumor size, mitotic counts, tumor grade, Ki-67 labeling index (LI), 7 KIT mutation type, 4,8,9 p16 inactivation 10 and overexpression of cell-cycle regulators such as cyclin A, cyclin B1 and cdc2. 11 Angiogenesis is one of the key steps in the growth and metastasis of solid tumors. 12,13 Angiogenesis is induced by the paracrine release of angiogenic molecules from tumor cells and stromal cells.…”

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confidence: 99%

Prognostic significance of angiogenesis in gastrointestinal stromal tumor

et al. 2007

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Angiogenesis is important in the growth and metastasis of various kinds of solid tumors. To investigate the potential role of angiogenesis in gastrointestinal stromal tumor (GIST), an immunohistochemical analysis was performed in 95 cases of GISTs for microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression. MVD was evaluated with immunohistochemical staining for CD31. A high level of MVD was significantly correlated with overexpression of VEGF, tumor location (intestine4stomach), tumor size (Z5 cm), tumor grade (high4intermediate4low grade) (P ¼ o0.0001, 0.0422, 0.0006, 0.0359, respectively). Of the 70 GISTs analyzed, KIT exon 11 mutations were detected in 45 cases (64.3%) and KIT exon 9 mutations in two cases (2.9%). No mutations were found in KIT exons 13 and 17, and platelet-derived growth factor receptor-alpha exons 12 and 18. Interestingly, VEGF expression level was significantly higher in the non-KIT exon 11 mutant group than in the KIT exon 11 mutant group (P ¼ 0.0266). In univariate analysis, tumor grade (high grade), tumor size (Z5 cm), mitotic count (Z5/50 high-power fields), Ki-67 labeling index (Z4.6%), MVD (Z7.0/0.95 mm 2 ) and VEGF expression (high) were significantly associated with a shorter period of disease-free survival (P ¼ o0.0001, 0.0199, 0.0055 0.0027, 0.0028 and 0.0302, respectively). In multivariate analysis, tumor grade and MVD were identified as independent worse prognostic factors (P ¼ 0.0007, 0.0152, respectively). In conclusion, our results suggest that the evaluation of MVD and VEGF expression is useful for predicting the aggressive biologic behavior of GIST, and that angiogenesis associated with VEGF may play an important role, at least in part, in the progression of GIST. Modern Pathology (2007) 20, 529-537.

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Prognostic significance of expressions of cell-cycle regulatory proteins in gastrointestinal stromal tumor and the relevance of the risk grade

Cited by 123 publications

References 33 publications

Ki67 and p53 in gastrointestinal stromal tumors - GIST

Ki67 and p53 in gastrointestinal stromal tumors - GIST

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

Prognostic significance of angiogenesis in gastrointestinal stromal tumor

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