Low ING4 protein expression detected by paraffin-section immunohistochemistry is associated with poor prognosis in untreated patients with gastrointestinal stromal tumors

Abstract

Background Inhibitor of growth 4 (ING4) has deserved attention as a tumor suppressor gene in many malignant tumors. In our study, we investigated ING4 immunoexpression in gastrointestinal stromal tumors (GISTs) and its prognostic value. Method The expression of ING4 and Ki67 was investigated in 41 samples of various risk gastrointestinal stromal tumors by immunohistochemical technique. The associations of ING4 expression and clinicopathological parameters, and prognosis of the patients, were analyzed by multivariate Cox regression analysis. Results ING4 expression showed a decreased trend from lower-risk to high-risk gastrointestinal stromal tumors, and an opposite trend for Ki67 expression. In lower-risk tumors, it was found the expression level of ING4 was 78.95 % ± 27.90 % and that of Ki67 was 4.42 % ± 3.75 %. However, in high-risk tumors, the expression level of ING4 was 9.23 % ± 7.66 % and that of Ki67 was 18.50 % ± 9.09 %. There was a strongly negative correlation between the expression levels of ING4 and Ki67. A significant difference was observed in the expression of ING4 between invasion and non-invasion (p \ 0.001). The expression of ING4 was markedly correlated with tumor size (p \ 0.001), mitotic index (p \ 0.001), tumor necrosis (p = 0.021), invasion (p \ 0.001), recurrence and metastasis (p = 0.021), and mortality (p \ 0.001). Conclusion The low expression level of ING4 protein was correlated with high-risk GISTs. ING4 might be involved in the progression of GISTs and inhibit its invasion. ING4 might be one of the prognostic indicators in GISTs.

ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer

“…The reduced expression of tumor suppressor ING4 has been reported in various malignancies, and down-regulation of ING4 is correlated with increased tumor metastasis, advanced TMN stages and poor patients survival in melanoma [18], gastric cancer [19] and breast cancer [20]. In the present study, we showed that both ING4 mRNA and protein expressions were lower in CRC tissues when compared with paired normal colon tissues.…”

The diagnostic and prognostic utility of dog1 expression on gastrointestinal stromal tumors

“…The clinicopathological features [age, gender, risk group, mitotic count in 50 high power fields (HPFs), tumor size, tumor location, growth pattern, cellularity, nuclear pleomorphism, ulceration, hemorrhage, necrosis, cell type, surgical/biopsy procedure type, and ki-67 proliferation index] were achieved from the original pathology reports. risk-groups had been established and adopted according to the criteria of Fletcher et al (16) based on tumor size and mitotic count in 50 HPFs. In the present study, the cases were divided into two groups as the "lower-risk group" and "high-risk group" to predict the prognosis of GISTs.…”

Keep‐ING balance: Tumor suppression by epigenetic regulation

“…ING4 is mainly lost or downregulated at the RNA level in human cancers. These include astrocytic tumors of the central nervous system [171,172], breast cancer [75,168,173–175], malignancies of the gastrointestinal tract [176–178], HNSCC [179,180], HCC [181,182], melanoma [75,183], lung [75], ovarian [75] and prostate cancer [75]. Like ING1 [80], ING4 downregulation correlates with higher WHO grades of malignancy in astrocytoma [172], with unfavorable prognosis of breast cancer patients [89,173,184] and with angiogenesis in multiple cancer types [106,184–190] and other diseases [191].…”