Document Type: Original Research
Post graduate, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, India
Professor, Department of Pathology, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, India
Background and Objective: This study was undertaken to analyze the immunohistochemical expression of fibroblast growth factor receptor (FGFR3) in urothelial carcinoma and correlate its expression with the pathological stage, recurrence and other clinicopathological parameters.
Material and Methods: A retrospective study was undertaken on paraffin blocks of 55consecutiveurothelial carcinoma specimens in 28 months received in Sri Ramachandra Medical College, Chennai, India. Blocks with the sections containing the tumor and adjacent normal epithelium were chosen for the immunohistochemical (IHC) study of FGFR3.
Results: IHC expression of FGFR3 in high grade (HG) invasive urothelial carcinoma was positive in 18% cases, 66.7% of HG non-invasive urothelial and 82.6% of low grade (LG) non-invasive urothelial carcinomas. The FGFR3 expression was presented in 78.1% of non-invasive carcinoma. In case of invasive urothelial carcinoma, the FGFR3 positivity was observed in 18.2% of tumors (P<0.05). FGFR3 expression in LG tumors was positive in 82.6 % of the cases whereas 32.3% of HG cases were positive for FGFR3 (P<0.05). FGFR3 was expressed in 14.3 % of HG invasive tumors which recurred. HG non-invasive tumors were positive for FGFR3 in 80% of the cases. LG non-invasive tumors were positive for FGFR3 in 72.7% of cases (P<0.05).
Conclusion: The expression of FGFR3 is higher in low grade, non-invasive tumors and recurrent non-invasive tumors. The targeted therapy for FGFR3 may be used as one of the modes of treatment for urothelial carcinoma. It can also be used as a marker to determine the grade in difficult cases and the risk of recurrence.
- Jemal A, Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Pathology and genetics of tumors of the urinary system and male genital organs. World Health Organization Classi. 2004.
- Billerey C, Chopin D, Aubriot-Lorton M, Ricol D, Gil Diez de Medina S, Van Rhijn B et al. Frequent FGFR3 Mutations in Papillary Non-Invasive Bladder (pTa) Tumors.
Am J Pathol.2001; 158(6):1955-1959.
- Tomlinson DC, Baldo O, Harnden P, Knowles MA. FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J PATHOL. 2007; 213(1):91-8.
- Maeng YH, Eun SY, Huh JS. Expression of fibroblast growth factor receptor 3 in the recurrence of non-muscle-invasive urothelial carcinoma of the bladder.Korean J Urol. 2010; 51(2):94-100.
- Lee HJ, Kang HJ, Kim KM, Yu ES, Kim KH, Kim SM, Kim TW, Shim JH, Lim YS, Lee HC, Chung YH. Fibroblast growth factor receptor isotype expression and its association with overall survival in patients with hepatocellular carcinoma. ClinMolHepatol. 2015 Mar;21(1):60.
- Lee H, Douglas-Jones AG, Morgan JM, Jasani B. The effect of fixation and processing on the sensitivity of oestrogen receptor assay by immunohistochemistry in breast carcinoma. J ClinPathol. 2002 Mar 1;55(3):236-8
- Rafique M, Javed AA. Clinico-pathological features of bladder carcinoma: experience from a tertiary care hospital of Pakistan.INT UROL NEPHROL. 2006;38(2):247-50.
- El Mawla NG, El Bolkainy MN, Khaled HM. Bladder cancer in Africa: update. SeminOncol 2001; 28(2):174-178.
- Poletajew S, Walędziak M, Fus Ł, Pomada P, Ciechańska J, Wasiutyński A. Urothelial bladder carcinoma in young patients is characterized by a relatively good prognosis.Ups J Med Sci. 2012;117(1):47-51.
- Huang H, Sun M, Li X, Jin J. Urothelial carcinoma of the bladder in patients aged 30 years or younger: clinicopathological analysis and expression of fibroblast growth factor receptor 3 (FGFR3) of 45 cases.Med Oncol. 2015; 32(5):137.
- Mandhani A, Gupta P, Jain M, Kapoor R, Muruganandham K, Srivastava A. Impact of age and gender on the clinicopathological characteristics of bladder cancer. Indian J Urol. 2009; 25(2):207.
- Biswas RR, Mangal S, Guha D, Basu K, Karmakar D. An epidemiological study of cases of urothelial carcinoma of urinary bladder in a tertiary care centre. J Krishna Institute of Med Sci. 2013; 2(1):82-.
- Spruck CH, Rideout WM, Olumi AF, Ohneseit PF, Yang AS, Tsai YC et al. Distinct pattern of p53 mutations in bladder cancer: relationship to tobacco usage. Cancer Res. 1993; 53(5):1162-6.
- Gómez-Román JJ, Saenz P, González JC, Escuredo K, Santa Cruz S, Junquera C et al. Fibroblast growth factor receptor 3 is overexpressed in urinary tract carcinomas and modulates the neoplastic cell growth. Clin Cancer Res. 2005; 11(2):459-65.
- Poyet C, Hermanns T, Zhong Q, Drescher E, Eberli D, Burger M et al. Positive fibroblast growth factor receptor 3 immunoreactivity is associated with low-grade non-invasive urothelial bladder cancer. Oncol Lett. 2015; 10(5):2753-60.
- Matsumoto M, Ohtsuki Y, Ochii K, Seike Y, Iseda N, Sasaki T et al. Fibroblast growth factor receptor 3 protein expression in urothelial carcinoma of the urinary bladder, exhibiting no association with low-grade and/or non-invasive lesions. Oncol Rep. 2004; 12(5):967-71.
- Bodoor K, Ghabkari A, Jaradat Z, AlKhateeb A, Jaradat S, Al-Ghazo MA et al. FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population. Cancer Epidemiol. 2010; 34(6):724-32.
- Guancial EA, Werner L, Bellmunt J, Bamias A, Choueiri TK, Ross R et al. FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder. Cancer Med. 2014; 3(4):835-44.
- Tavakkoly-Bazzaz J, Salami SA, Pourmand MR, Mansouri F, Mashahdi R, Pourmand G. Differential expression of FGFRs signaling pathway components in bladder cancer: A step toward personalized medicine. Balkan J Med Genet. 2017 Dec 29;20(2):75-81.
- Kobayashi H, Kikuchi E, Mikami S, Maeda T, Tanaka N, Miyajima A, Nakagawa K, et al. Long term follow-up in patients with initially diagnosed low grade Ta non-muscle invasive bladder tumors: tumor recurrence and worsening progression. BMC urol. 2014; 14(1):5.
- Mhawech-Fauceglia P, Cheney RT, Fischer G, Beck A, Herrmann FR. FGFR3 and p53 protein expressions in patients with pTa and pT1 urothelial bladder cancer.Eur J SurgOncol. 2006; 32(2):231-7.
- vanOers JM, Wild PJ, Burger M, Denzinger S, Stoehr R, Rosskopf E et al. FGFR3 mutations and a normal CK20 staining pattern define low-grade noninvasive urothelial bladder tumors.Eur Urol. 2007; 52(3):760-8.
- Ahmad F, Mahal V, Verma G, Bhatia S, Das BR. Molecular investigation of FGFR3 gene mutation and its correlation with clinicopathological findings in Indian bladder cancer patients. Cancer Rep.2018 ;1(3):e1130.
- . van Rhijn BW, Lurkin I, Radvanyi F, Kirkels WJ, van der Kwast TH, Zwarthoff EC. The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer research. 2001 Feb 2;61(4):1265-8.
- Hernández S, López-Knowles E, Lloreta J, Kogevinas M, Amorós A, TardónA et al. Prospective study of FGFR3 mutations as a prognostic factor in nonmuscle invasive urothelial bladder carcinomas. J ClinOncol. 2006; 24(22):3664-71.
- Turo R, Harnden P, Thygesen H, Fleischmann A, Thalmann GN, Seiler R et al. FGFR3 expression in primary invasive bladder cancers and matched lymph node metastases. J Urol. 2015; 193(1):325-30.
- Rotterud R, Fossa SD, Nesland JM. Protein networking in bladder cancer: immunoreactivity for FGFR3, EGFR, ERBB2, KAI1, PTEN, and RAS in normal and malignant urothelium. HistolHistopathol. 2007; 22(4-6):349-64.
- Burry RW. Controls for immunocytochemistry: an update. J HistochemCytochem 2011;59(1):6-12.