The Expressions of E2F1 and p53 in Gastrointestinal Stromal Tumors and Their Prognostic Significance
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Background : E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors. Methods : Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate. Results : 1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008). Conclusions : E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.
Abstract
Background : E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors. Methods : Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate. Results : 1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008). Conclusions : E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.
참고문헌 (24)
- Thomas RM, "Gastrointestinal cancer; incidence and prognosis by histologic type, SEER population-based data 1973-1987", Cancer, 75, pp.154~170 (1995)
- Kindblom LG, "Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal", Am J Pathol, 152, pp.1259~1269 (1998)
- Miettinen M, "Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis and differential diagnosis", Arch Pathol Lab Med, 130, pp.1466~1478 (2006)
- Fletcher CD, "Diagnosis of gastrointestinal stromal tumors: a consensus approach", Hum Pathol, 33, pp.459~465 (2002)
- Nakamura N, "Prognostic significance of expressions of cell-cycle regulatory proteins in gastrointestinal stromal tumor and the relevance of the risk grade", Hum Pathol, 36, pp.828~837 (2005)
- Dimova DK, "The E2F transcriptional network: old acquaintances with new faces", Oncogene, 24, pp.2810~2826 (2005)
- Haller F, "Prognostic role of E2F1 and members of the CDKN2A network in gastrointestinal stromal tumors", Clin Cancer Res, 11, pp.6589~6597 (2005)
- Sherr CJ, "The INK4a", ARF network in tumour suppression, 2001, pp.2, 731~737
- Stevens C, "E2F and cell cycle control: a double-edged sword", Arch Biochem Biophys, 412, pp.157~169 (2003)
- Attwooll C, "The E2F Family: specific functions and overlapping interests", EMBO J, 23, pp.4709~4716 (2004)
- LaThangue NB, "The yin and yang of E2F-1: balancing life and death", Nat Cell Biol, 5, pp.587~589 (2003)
- Eymin B, "Distinct pattern of E2F1 expression in humnan lung tumours: E2F1 is up-regulated in small cell lung carcinoma", Oncogene, 20, pp.1678~1687 (2001)
- Zhang SY, "E2F1: a proliferative marker of breast neoplasia", Cancer Epidemiol Biomarkers Prev, 9, pp.395~401 (2000)
- Saiz AD, "Immunohistochemical expression of cyclin D1, E2F1, and Ki-67 in benign and malignant thyroid lesions", J Pathol, 198, pp.157~162 (2002)
- 김지연, "난소 상피 종양에서 G1", S 세포주기 조절단백의 변화, 2006, pp.40(4), 274~281[DOI]
- Zacharators P, "Distinct expression patterns of the transcription factor E2F1 in relation to tumour growth parameters in common human carcinomas", J Pathol, 203, pp.744~753 (2004)
- Rabbani F, "Prognostic significance of transcription factor E2F-1 in bladder cancer: genotypic and phenotypic characterization", J Natl Cancer Inst, 91, pp.874~881 (1999)
- Kononen J, "Tissue microarrays for high-throughput molecular profiling of tumor specimens", Nat Med, 4, pp.844~847 (1998)
- Meara RS, "Prediction of aggressiveness of gastrointestinal stromal tumours based on immunostaining with bcl-2, Ki-67 and p53", Cytopathology, 18, pp.283~289 (2007)
- Dyson N, "The regulation of E2F by pRB-family members", Genes Dev, 12, pp.2245~2262 (1998)
- Sharma N, "Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 Is Essential for G1", S Progression and Cellular Transformation, 2006, pp.281, 36124~36131
- Al-Bozom IA, "p53 overexpresion in gastrointestinal stromal tumors", Pathol Int, 51, pp.519~523 (2001)
- Miettinen M, "Gastrointestinal stromal tumors: pathology and prognosis at different sites", Semin Diag Pathol, 23, pp.70~83 (2006)
- Reth JD, "Extragastrointestinal (soft tissue) stromal tumors. An analysis of 48 cases with emphasis on histological predictors of outcome", Mod Pathol, 13, pp.577~585 (2000)