IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes. Methods: We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed. Results: Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with diseasespecific survival. Conclusions: IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.
Abstract
Background: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes. Methods: We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed. Results: Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with diseasespecific survival. Conclusions: IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.
참고문헌 (29)
- Eble JN, "Pathology and genetics of tumours of the urinary system and male genital organs", pp.9~87 (2004), IARC Press
- Jiang Z, "Combination of quantitative IMP3 and tumor stage: a new system to predict metastasis for patients with localized renal cell carcinomas", Clin Cancer Res, 14, pp.5579~5584 (2008)
- Jiang Z, "Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study", Lancet Oncol, 7, pp.556~564 (2006)
- Jiang Z, "Oncofetal protein IMP3: a novel molecular marker that predicts metastasis of papillary and chromophobe renal cell carcinomas", Cancer, 112, pp.2676~2682 (2008)
- Annual report of cancer statistics in Korea in 2009, "The Korea Central Cancer Registry, National Cancer Center", Ministry of Health and Welfare, ~ (2011)
- Bostwick DG, "Urologic surgical pathology" (2008), Mosby
- Visapaa H, "Correlation of Ki-67 and gelsolin expression to clinical outcome in renal clear cell carcinoma", Urology, 61, pp.845~850 (2003)
- Hoffmann NE, "External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma", Cancer, 112, pp.1471~1479 (2008)
- Jeng YM, "RNA-binding protein insulin-like growth factor II mRNA-binding protein 3 expression promotes tumor invasion and predicts early recurrence and poor prognosis in hepatocellular carcinoma", Hepatology, 48, pp.1118~1127 (2008)
- Nielsen J, "A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development", Mol Cell Biol, 19, pp.1262~1270 (1999)
- Yaniv K, "The involvement of a conserved family of RNA binding proteins in embryonic development and carcinogenesis", Gene, 287, pp.49~54 (2002)
- Li C, "Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations", Mod Pathol, 20, pp.1263~1268 (2007)
- Li L, "Expression of RNA-binding protein IMP3 (KOC) in benign urothelium and urothelial tumors", Hum Pathol, 39, pp.1205~1211 (2008)
- Riener MO, "IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas", Hum Pathol, 40, pp.1377~1383 (2009)
- Yuan RH, "Diffuse expression of RNA-binding protein IMP3 predicts high-stage lymph node metastasis and poor prognosis in colorectal adenocarcinoma", Ann Surg Oncol, 16, pp.1711~1719 (2009)
- 송대현, "Insulin-like Growth Factor II mRNA-Binding Protein 3 Expression in Benign and Premalignant Lesions and Carcinomas of the Stomach", Journal of Pathology and Translational Medicine, 45(4), pp.379~385 (2011), 대한병리학회
- Shvarts O, "p53 is an independent predictor of tumor recurrence and progression after nephrectomy in patients with localized renal cell carcinoma", J Urol, 173, pp.725~728 (2005)
- Zigeuner R, "Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: a systematic analysis of primary and metastatic tumor tissue", Urology, 63, pp.651~655 (2004)
- Noon AP, "p53 and MDM2 in renal cell carcinoma: biomarkers for disease progression and future therapeutic targets?", Cancer, 116, pp.780~790 (2010)
- Escudier B, "Sorafenib in advanced clear-cell renal-cell carcinoma", N Engl J Med, 356, pp.125~134 (2007)
- Bukowski RM, "Prognostic factors for survival in metastatic renal cell carcinoma: update 2008", Cancer, 115(10 Suppl), pp.2273~2281 (2009)
- Fisher R, "Current and future systemic treatments for renal cell carcinoma", Semin Cancer Biol, 23, pp.38~45 (2013)
- Noubissi FK, "Wnt signaling stimulates transcriptional outcome of the Hedgehog pathway by stabilizing GLI1 mRNA", Cancer Res, 69, pp.8572~8578 (2009)
- Vikesaa J, "RNA-binding IMPs promote cell adhesion and invadopodia formation", EMBO J, 25, pp.1456~1468 (2006)
- Haitel A, "mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters", Clin Cancer Res, 6, pp.1840~1844 (2000)
- Dudderidge TJ, "Mcm2, Geminin, and KI67 define proliferative state and are prognostic markers in renal cell carcinoma", Clin Cancer Res, 11, pp.2510~2517 (2005)
- Hao S, "The oncofetal protein IMP3: a novel molecular marker to predict aggressive meningioma", Arch Pathol Lab Med, 135, pp.1032~1036 (2011)
- Chen LT, "The correlation between insulin-like growth factor II mRNA binding protein 3 expression in hepatocellular carcinoma and prognosis", Hepatogastroenterology, 60, pp.553~556 (2013)
- Hartmann EM, "Increased tumor cell proliferation in mantle cell lymphoma is associated with elevated insulin-like growth factor 2 mRNA-binding protein 3 expression", Mod Pathol, 25, pp.1227~1235 (2012)
