The Cyclin-Dependent Kinase Inhibitor, p27kip1, Has No Correlation with the Malignant Potential of GIST

Abstract

Background: Tumor size and mitotic activity are characteristically associated with the malignant potential and prognosis of gastrointestinal stromal tumors (GIST). However, since neither small tumor size nor low mitotic activity can rule out malignancy, additional factors that may predict malignant behavior have been suggested. Aim: To evaluate the correlation between the cyclin-dependent kinase inhibitor (CDI), p27^kip1, expression and the malignant potential of GIST. Methods: Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67 in surgical material obtained from 36 patients with GIST. p27^kip1 staining intensity and the percentage of positive cells were investigated for association with the malignancy risk, pathological features, overall survival, and disease-free survival. Histologic grade was assigned by spindle vs. epithelioid cell histology, mucosal invasion, tumor cell necrosis or atypia and the number of mitoses. Results: In the multivariate model, p27^kip1 expression was not significantly associated with any of the variables examined except Kit protein-CD117 (r = 0.37, p = 0.03). Comparative evaluation of p27^kip1 expression in GIST cells revealed higher levels of p27^kip1 in patients who died compared to those who survived (2.04 ± 0.54 vs. 1.3 ± 0.99, p = 0.1). Conclusion: The CDI p27^kip1 was not associated with malignancy of GISTs and did not serve as a predictor of survival.

Stage and histological grade of gastrointestinal stromal tumors based on a new approach are strongly associated with clinical behaviors

“…There is a strong need for a practical and reliable classification system that can be used to predict the clinical course of GIST patients and facilitate the design of treatment regimen. On the basis of previous investigations and our preliminary work, [10][11][12][13][14][15][16][17][18] we collected the pathological and clinical data of a large number of GIST patients and assessed a simple and new grading and staging system. Patients from multiple hospitals were analyzed because it is expected to be more likely free of selection bias, which could occur in different hospitals or treatment trials.…”

“…Clinically, some patients with malignant GIST are highly aggressive, developing recurrence within short time after surgical removal of the primary tumor, whereas others can be treated effectively by surgical resection alone or had a long latency to develop recurrence. Many investigators made efforts to grade [10][11][12][13][14][15] and/or stage GISTs. 11,[16][17][18] On the basis of these previous reports and our preliminary study, we selected 12 parameters that not only had predictive value for malignancy, but also had value to stage and grade GISTs effectively.…”

Roles of mTOR and p-mTOR in Gastrointestinal Stromal Tumors

“…The deletion of PTEN protein has the close relationship with the occurrence and development of GIST (Tamguney and Stokoe, 2007;Carracedo and Pandolfi, 2008). P27 can block transitions of the G1/S phase in the cell cycle and can inhibit cell proliferation; thus, the deletion or reduction of P27 protein expression can result in the occurrence of tumor (Shirin et al, 2007;Wang et al, 2010). mTOR can enhance the expression of hypoxia inducible factor HIF-1a and promote the expression of VEGF, which is closely related to tumor proliferation and metastasis (Benjamin et al, 2011).…”

Sporadic Pediatric GIST With Novel Gene Mutation

“…Imatinib and newer tyrosine kinase inhibitors have successfully been used for medical management of malignant or recurrent disease and debulking before resection [13]. Risk assessment is based upon tumor size and mitotic count [14] and is vital for follow-up strategy as given below: 1) Very low risk (size less than 2 cm, mitotic count less than 5/50 high power field HPF): No follow-up imaging is required 2) Low risk (size 2-5 cm, mitotic count less than 5/50 HPF): CT at 3 months after resection then clinical follow-up 3) Intermediate risk (size less than 5 cm, count 6-10 HPF or size 5-10 cm, count less than 5/50 HPF): CT at 3 months post resection, followed by every 6 months for 2 years, then annually up to 5 years 4) High risk (size greater than 5 cm, count more than 5/50 HPF or size 10 irrespective of count or count more than 10/50 PHF irrespective of size): CT every 3 months for 2 years, followed by 6 months for 2 years and then annually.…”