Prediction of aggressiveness of gastrointestinal stromal tumours based on immunostaining with bcl‐2, Ki‐67 and p53

Meara, R. S.; Cangiarella, Joan; Simsir, Aylin; Horton, Debra; Eltoum, Isam; Chhieng, David C.

doi:10.1111/j.1365-2303.2007.00505.x

Cited by 28 publications

(19 citation statements)

References 38 publications

(188 reference statements)

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“…However, the majority of these studies, as well as ours, were limited by the fact that most of the statistically significant variables based on univariate statistics are not statistically strong enough to 'surviveʼ a further multivariate analysis, leading to the heretic question of whether IHC does actually provide additional prognostic data in GISTs (18). Furthermore, we were unable to confirm the role of differentiation and cell-cycle regulatory proteins, such as Bcl-2, P16 and P53, as well as CD44, as prognostic factors, similar to previous studies (8,(21)(22)(23)(24). The reasons may be different antibodies, antigen retrieval or inter-observer variations of the immunohistochemical staining (10,11,15).…”

Section: Discussioncontrasting

confidence: 38%

Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors

Klieser

Pichelstorfer

Weyland

et al. 2016

Molecular and Clinical Oncology

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Abstract. The aim of this study was to provide a standardized risk stratification model for gastrointestinal stromal tumors (GISTs) based on tumor localization, tumor size, involved lymph nodes and metastases, as well as mitotic activity and other morphological and molecular markers, in order to improve the risk evaluation scheme for recurrence, metastatic spread and survival for patients with GIST. A total of 201 cases of patients with GIST were investigated according to standardized morphological markers, including nuclear pleomorphism, tumor cell necrosis, mucosal infiltration, ulceration, skeinoid fibers and growth pattern. In addition, all cases were immunohistochemically analyzed using a tissue microarray platform for various markers of differentiation (CD34, CD44, CD117, desmin, discovered on GIST 1, platelet-derived growth factor receptor α, S-100 and smooth muscle actin) and proliferation (B-cell lymphoma 2, P16, P53, phosphohistone H3 and Ki-67). These findings were correlated by uni-and multivariable analyses with clinicopathological characteristics, including recurrence, metastasis and survival. The general clinicopathological parameters of this GIST specimen cohort were comparable to previous studies. While several parameters exhibited clear associations to each other and to the defined clinical endpoints, the multivariate analysis reduced the number of relevant prognostic variables to localization, margin status, growth pattern and hematoxylin and eosin-based mitosis̸Ki-67-based proliferation of GISTs. With the exception of CD34, none of the applied markers of differentiation and proliferation were found to be independent prognostic markers in GIST and the classical risk factors of GIST remain important prognostic factors. Additionally, growth pattern may predict the risk of recurrence and metastasis in GIST patients. Additional independent molecular prognostic markers remain to be identified and validated.

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Section: Discussioncontrasting

confidence: 38%

Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors

Klieser

Pichelstorfer

Weyland

et al. 2016

Molecular and Clinical Oncology

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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%

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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“…37 Indeed, Meara et al go so far as to state that Ki-67 is not useful as a prognostic marker for GIST in FNA specimens. 38 Although tumor size, mitotic count, and Ki-67 index may help identify the malignant potential of GISTs, all GISTs should ultimately be managed as malignant neoplasms because even small GISTs with no observable mitoses have been shown to later acquire malignant characteristics. 11 It is very difficult to assess malignant potential based on cytomorphologic features alone, and this emphasizes the importance of special, ancillary immunochemical stains in making a final diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Endoscopic ultrasonography‐guided fine‐needle aspiration for diagnosing upper gastrointestinal submucosal lesions: A prospective study of 50 cases

Turhan

Aydog

Özın

et al. 2010

Diagnostic Cytopathology

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The objective was to assess EUS-FNA for diagnosing intramural upper GI tract lesions. The subjects were 50 patients (21M/29F) with upper GI submucosal lesions who underwent EUS-FNA at a referral center for GI system over a 12-month period. All cases were followed for 1 year after initial EUS-FNA. Cytologic diagnoses were categorized as benign, malignant, suspicious for malignancy, mesenchymal tumor, endocrine tumor, or nondiagnostic. All tumors were assessed for various cytomorphologic features. The accuracy of the initial FNA diagnoses was evaluated for each patient who also underwent subsequent histopathological examination of a core biopsy and/or surgical biopsy/resection material of the same lesion. According to the site of the lesions; while 84% of all esophageal lesions were diagnosed as mesenchymal; 67% of all gastric lesions were mesenchymal. The sole lesion was nonmesenchymal (benign cyst) in duodenum. The sensitivity, specificity, positive and negative predictive values, and accuracy of EUS-FNA for diagnosing submucosal mesenchymal tumors of the upper GI tract were 82.9, 73.3, 87.9, 64.7, and 80%, respectively. The corresponding values for nonmesenchymal lesions were 100, 85.7, 80, 100, and 90.9%. Our experience confirms that EUS-FNA is an extremely valuable tool for diagnosing submucosal lesions of the upper GI, and is particularly useful in cases where endoscopic forceps biopsy does not lead to diagnosis. Optimal results can be yielded by a close working relationship between the gastroenterologist and pathologist.

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Prediction of aggressiveness of gastrointestinal stromal tumours based on immunostaining with bcl‐2, Ki‐67 and p53

Abstract: According to our observations, p53 immunostaining may be useful in predicting the outcome of GIST diagnosed by FNA; Ki-67 and bcl-2 are not useful as prognostic markers for GIST in FNA specimens.

Cited by 28 publications

References 38 publications

Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors

Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors

Ki67 and p53 in gastrointestinal stromal tumors - GIST

Endoscopic ultrasonography‐guided fine‐needle aspiration for diagnosing upper gastrointestinal submucosal lesions: A prospective study of 50 cases

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