Cyclin H expression is increased in GIST with very-highrisk of malignancy

Abstract

BackgroundRisk estimation of gastrointestinal stromal tumours (GIST) is based on tumour size and mitotic rate according to the National Institutes of Health consensus classification. The indication for adjuvant treatment of patients with high risk GIST after R0 resection with small molecule inhibitors is still a controversial issue, since these patients represent a highly heterogeneous population. Therefore, additional prognostic indicators are needed. Here, we evaluated the prognostic value of cyclin H expression in GIST.MethodsIn order to identify prognostic factors of GIST we evaluated a single centre cohort of ninety-five GIST patients. First, GISTs were classified with regard to tumour size, mitotic rate and localisation according to the NIH consensus and to three additional suggested risk classifications. Second, Cyclin H expression was analysed.ResultsOf ninety-five patients with GIST (53 female/42 male; median age: 66.78a; range 17-94a) risk classification revealed: 42% high risk, 20% intermediate risk, 23% low risk and 15% very low risk GIST. In patients with high risk GIST, the expression of cyclin H was highly predictive for reduced disease-specific survival (p = 0.038). A combination of cyclin H expression level and high risk classification yielded the strongest prognostic indicator for disease-specific and disease-free survival (p ≤ 0.001). Moreover, in patients with tumour recurrence and/or metastases, cyclin H positivity was significantly associated with reduced disease-specific survival (p = 0.016) regardless of risk-classification.ConclusionOur data suggest that, in addition to high risk classification, cyclin H expression might be an indicator for "very-high risk" GIST.

Positive cyclin T expression as a favorable prognostic factor in treating gastric gastrointestinal stromal tumors

“…Along with the factors of large tumor size and high mitotic rate presented in the NIH consensus, several studies have defined other poor prognostic factors, Cyclin T1 such as epithelioid type, increased expression of cytoplasmic HuR and cyclin A, and a high Ki67 ratio (24)(25)(26)(27). Increased expression of cyclin H was also a poor prognostic factor in high-risk GIST patients (23). The present results showed that cyclin T1 may be another potential prognostic predictor for gastric GIST patients.…”

“…The expression of cyclins A, B, D and E appear to be associated with high-grade disease but not with the clinical outcome (20-22). In addition, cyclin H-positive patients have a poor prognosis when they have high-risk GIST and when they exhibit metastasis or recurrent disease (23). However, there are few effective clinical predictors for gastric GIST.…”

The role of FBXW7, a cell-cycle regulator, as a predictive marker of recurrence of gastrointestinal stromal tumors

“…Recent reports showed that cyclin H and p16 are indicators of high-risk GIST [24,25]. Most recently, Ihle et al [11] revealed that expression of cell-cycle regulators, such as cyclin D1, CDK4, p21, and p16, was associated with recurrence in 400 high-risk patients with GISTs.…”

Cyclins and Cell Cycle Control in Cancer and Disease

“…89 Elevated cyclin H is associated with very high-risk gastrointestinal stromal tumors, and reduced or absent cyclin H expression correlates with lower proliferation in B-cell lymphoma. 90,91 The transcriptional regulation elicited by the CAK complex (cyclin H-CDK7-Mat1) impacts embryonic stem (ES) cell differentiation. The complex activates CDK1, CDK2, CDK4, and CDK6 through phosphorylation of the T-loop.…”