Significance of Intratumoral Fibrosis in Clear Cell Renal Cell Carcinoma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Intratumoral fibrosis (ITF) is a frequent histologic finding in solid organ tumors. Renal cell carcinoma (RCC) is a highly vascularized tumor with different shapes and degrees of ITF and inflammation. ITF is a poor prognostic factor, especially in breast cancer, and is related to intratumoral necrosis (ITN) and intratumoral inflammation (ITI). However, the significance of ITF in RCC has not been fully studied. In this study, we evaluate the relationships between ITF and other clinicopathologic parameters associated with RCC prognosis. Methods: ITF was evaluated in 204 clear cell renal cell carcinoma (CCRCC) specimens according to presence and grade of fibrosis, degree of ITI, and presence of ITN. Lysyl oxidase (LOX) expression in tumor cells was also evaluated with clinicopathologic parameters. Results: Among 204 CCRCC cases, 167 (81.7%) showed ITF, 71 (34.8%) showed ITI, 35 (17.2%) showed ITN, and 111 (54.4%) showed LOX expression. ITF correlated with Fuhrman nuclear grade (p = .046), lymphovascular invasion (LVI) (p = .027), and ITN (p = .036). Patients with ITF had a poor five-year overall survival rate (p = .104). Conclusions: ITF is related to other poor prognostic factors in CCRCC, such as Fuhrman nuclear grade, ITN, and LVI, but ITF itself had no significant correlation with prognosis of CCRCC.
Abstract
Background: Intratumoral fibrosis (ITF) is a frequent histologic finding in solid organ tumors. Renal cell carcinoma (RCC) is a highly vascularized tumor with different shapes and degrees of ITF and inflammation. ITF is a poor prognostic factor, especially in breast cancer, and is related to intratumoral necrosis (ITN) and intratumoral inflammation (ITI). However, the significance of ITF in RCC has not been fully studied. In this study, we evaluate the relationships between ITF and other clinicopathologic parameters associated with RCC prognosis. Methods: ITF was evaluated in 204 clear cell renal cell carcinoma (CCRCC) specimens according to presence and grade of fibrosis, degree of ITI, and presence of ITN. Lysyl oxidase (LOX) expression in tumor cells was also evaluated with clinicopathologic parameters. Results: Among 204 CCRCC cases, 167 (81.7%) showed ITF, 71 (34.8%) showed ITI, 35 (17.2%) showed ITN, and 111 (54.4%) showed LOX expression. ITF correlated with Fuhrman nuclear grade (p = .046), lymphovascular invasion (LVI) (p = .027), and ITN (p = .036). Patients with ITF had a poor five-year overall survival rate (p = .104). Conclusions: ITF is related to other poor prognostic factors in CCRCC, such as Fuhrman nuclear grade, ITN, and LVI, but ITF itself had no significant correlation with prognosis of CCRCC.
참고문헌 (33)
- Siegel RL, "Cancer statistics, 2016", CA Cancer J Clin, 66, pp.7~30 (2016)[DOI]
- 정재영, "Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea", Cancer Research and Treatment, 49(3), pp.607~615 (2017), 대한암학회
- Srigley JR, "The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia", Am J Surg Pathol, 37, pp.1469~1489 (2013)[DOI]
- Gerlinger M, "Intratumor heterogeneity and branched evolution revealed by multiregion sequencing", N Engl J Med, 366, pp.883~892 (2012)[DOI]
- Beksac AT, "Heterogeneity in renal cell carcinoma", Urol Oncol, 35, pp.507~515 (2017)[DOI]
- Hiley C, "Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine", Genome Biol, 15, pp.453~ (2014)[DOI]
- Palsdottir HB, "Incidental detection of renal cell carcinoma is an independent prognostic marker: results of a long-term, whole population study", J Urol, 187, pp.48~53 (2012)[DOI]
- Steeg PS, "Tumor metastasis: mechanistic insights and clinical challenges", Nat Med, 12, pp.895~904 (2006)[DOI]
- Cox TR, "LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis", Cancer Res, 73, pp.1721~1732 (2013)[DOI]
- Bissell MJ, "Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment?", Cancer Cell, 7, pp.17~23 (2005)
- Paszek MJ, "Tensional homeostasis and the malignant phenotype", Cancer Cell, 8, pp.241~254 (2005)[DOI]
- Cox TR, "Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer", Dis Model Mech, 4, pp.165~178 (2011)[DOI]
- Lucero HA, "Lysyl oxidase: an oxidative enzyme and effector of cell function", Cell Mol Life Sci, 63, pp.2304~2316 (2006)[DOI]
- Chang HM, "Activin A-induced increase in LOX activity in human granulosa-lutein cells is mediated by CTGF", Reproduction, 152, pp.293~301 (2016)[DOI]
- Mujtaba SS, "Fibrotic focus in breast carcinomas: relationship with prognostic parameters and biomarkers", Ann Surg Oncol, 20, pp.2842~2849 (2013)[DOI]
- Hasebe T, "Prognostic significance of fibrotic focus in invasive ductal carcinoma of the breast: a prospective observational study", Mod Pathol, 15, pp.502~516 (2002)[DOI]
- Wynn TA, "Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases", J Clin Invest, 117, pp.524~529 (2007)[DOI]
- Keeley EC, "Fibrocytes: bringing new insights into mechanisms of inflammation and fibrosis", Int J Biochem Cell Biol, 42, pp.535~542 (2010)[DOI]
- Butcher DT, "A tense situation: forcing tumour progression", Nat Rev Cancer, 9, pp.108~122 (2009)[DOI]
- Geissler K, "Immune signature of tumor infiltrating immune cells in renal cancer", Oncoimmunology, 4, pp.e985082~ (2015)[DOI]
- Fang LY, "Infiltrating macrophages promote prostate tumorigenesis via modulating androgen receptor-mediated CCL4-STAT3 signaling", Cancer Res, 73, pp.5633~5646 (2013)[DOI]
- Minarik I, "Regulatory T cells, dendritic cells and neutrophils in patients with renal cell carcinoma", Immunol Lett, 152, pp.144~150 (2013)[DOI]
- Yang Z, "Infiltrating macrophages increase RCC epithelial mesenchymal transition (EMT) and stem cell-like populations via AKT and mTOR signaling", Oncotarget, 7, pp.44478~44491 (2016)
- Hasebe T, "New prognostic histological parameter of invasive ductal carcinoma of the breast: clinicopathological significance of fibrotic focus", Pathol Int, 50, pp.263~272 (2000)[DOI]
- Delahunt B, "Histological indicators of prognosis", Pathology, 19, pp.258~263 (1987)[DOI]
- Frank I, "An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score", J Urol, 168, pp.2395~2400 (2002)[DOI]
- Kagan HM, "Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell", J Cell Biochem, 88, pp.660~672 (2003)[DOI]
- Egeblad M, "Dynamic interplay between the collagen scaffold and tumor evolution", Curr Opin Cell Biol, 22, pp.697~706 (2010)[DOI]
- Ma XJ, "Gene expression profiling of the tumor microenvironment during breast cancer progression", Breast Cancer Res, 11, pp.R7~ (2009)[DOI]
- Ramaswamy S, "A molecular signature of metastasis in primary solid tumors", Nat Genet, 33, pp.49~54 (2003)[DOI]
- Calvo A, "Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis", Oncogene, 27, pp.5373~5384 (2008)[DOI]
- Qiu TH, "Global expression profiling identifies signatures of tumor virulence in MMTV-PyMT-transgenic mice: correlation to human disease", Cancer Res, 64, pp.5973~5981 (2004)[DOI]
- Jensen BV, "Extracellular matrix building marked by the N-terminal propeptide of procollagen type I reflect aggressiveness of recurrent breast cancer", Int J Cancer, 98, pp.582~589 (2002)[DOI]