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http://dx.doi.org/10.7314/APJCP.2013.14.1.15

c-KIT Positive Schistosomal Urinary Bladder Carcinomas are Frequent but Lack KIT Gene Mutations

Shams, Tahany M. (Department of Pathology, Faculty of Medicine, Suez Canal University)
Metawea, Mokhtar (Department of Urology, Faculty of Medicine, Suez Canal University)
Salim, Elsayed I. (Department of Zoology, Faculty of Science, Tanta University)

Publication Information

Asian Pacific Journal of Cancer Prevention / v.14, no.1, 2013 , pp. 15-20 More about this Journal

Abstract

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

Keywords

c-KIT; immunostaining; gene mutation; schistosomiasis; squamous cell carcinoma; urinary bladder;

Citations & Related Records

Reference

1	Natali PG, Nicotra MR, Sures I, et al (1992b). Breast cancer is associated with loss of the c-KIT oncogene product. Int J Cancer, 52, 713-7. DOI
2	Pan CX, Yang XJ, Lopez-Beltran A, et al (2005). c-KIT expression in small cell carcinoma of the urinary bladder: prognostic and therapeutic implications. Mod Pathol, 18, 320-3. DOI ScienceOn
3	Pardanani A, Elliott M, Reeder T, et al (2003). Imatinib for systemic mast-cell disease. Lancet, 362, 535-6. DOI ScienceOn
4	Sabah M, Leader M, Kay E (2003). The problem with KIT: clinical implications and practical difficulties with CD117 immunostaining. Appl Immunohistochem Mol Morphol, 11, 56-61.
5	Savage DG, Antman KH (2002). Imatinib mesylate—a new oral targeted therapy. N Engl J Med, 346, 683-93. DOI ScienceOn
6	Sela GB, Kuten A, ELiezer SB, Ari EG, Izhak OB (2003) expression of HER2 and c-KIT in nasopharyngeal carcinoma: Implication for a new therapeutic approach. Mod Pathol, 16, 1035-40. DOI ScienceOn
7	Swellam M, Abd El-Aal AA, AbuGabel Kh M (2004). Deletions of p15 and p16 in schistosomal bladder cancer correlate with transforming growth factor- $\alpha$ expression. Clinical Biochemistry, 37, 1098-104. DOI ScienceOn
8	Tian Q, Frierson Jr HF, Krystal GW, et al (1999). Activating c-KIT gene mutations in human germ cell tumors. Am J Pathol, 154, 1643-7. DOI ScienceOn
9	Tsuura Y, Hiraki H, Watanabe K, et al (1994). preferential localization of c-KIT product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human:immunohistochemical study on formalin-fixed, paraffinembedded tissues. Virchows Arch, 424, 135-41.
10	Turner AM, Zsebo KM, Martin F, et al (1992). Nonhematopoietic tumor cell lines express stem cell factor and display c-KIT receptors. Blood, 80, 374-81.
11	Ullrich A, Schlessinger J (1990). Signal transduction by receptors with tyrosine kinase activity. Cell, 61, 203-12. DOI ScienceOn
12	Vliagoftis H, Worobec AS, Metcalfe DD (1997). The protooncogene c-KIT and c-KIT ligand in human disease. J Allergy Clin Immunol, 100, 435-40. DOI ScienceOn
13	Warren W, Biggs PJ, EI-Baz M, et al (1995). Mutations in the p53 gene in schistosomal bladder cancer: a study of 92 tumours from Egyptian patients and a comparison between mutational spectra from schistosomal and non-schistosomal urothelial tumours. Carcinogenesis, 16, 1181-9. DOI ScienceOn
14	Went PT, Dirnhofer S, Bundi M, et al (2004). Prevalence of KIT expression in human tumors. J Clin Oncol, 22, 4514-22. DOI ScienceOn
15	Heinrich MC, Blanke CD, Druker BJ, Corless CL (2002).Inhibition of KIT tyrosine kinase activity: a novel molecularapproach to the treatment of KIT-positive malignancies. JClin Oncol, 20, 1692-703. DOI ScienceOn
16	Yarden Y, Kuang WJ, Yang-Feng T, et al (1987). Human protooncogene c-KIT: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J, 6, 3341-51.
17	Zsebo KM, Williams DA, Geissler EN, et al (1990). Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-KIT tyrosine kinase receptor. Cell, 63, 213-24. DOI ScienceOn
18	Greene F, Page D, Fleming I, et al (2002). AJCC Cancer Staging Manual, 6th ed, Springer-Verlag, New York, NY,
19	Hirota S, Isozaki K, Moriyama Y, et al (1998). Gain-of-function mutations of c-KIT in human gastrointestinal stromal tumors. Sci, 279, 577-80. DOI ScienceOn
20	Holst VA, Marshall CE, Moskaluk CA, et al (1999). KIT protein expression and analysis of c-KIT gene mutation in adenoid cystic carcinoma. Mod Pathol. 12, 956-60.
21	Hornick JL, Fletcher CD (2002). Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution. Am J Clin Pathol, 117, 188-93. DOI ScienceOn
22	Hsu SM, Raine L, Fanger H (1981). Use of avidin-biotinperoxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem, 29, 577-80. DOI ScienceOn
23	Ingram DA, Yang FC, Travers JB, et al (2000) Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo. J Exp Med, 191, 181-8. DOI
24	Johnson BE, Fischer T, Fischer B (2003). Phase II study of imatinib in patients with small cell lung cancer. Clin Cancer Res, 9, 58807.
25	Lev S, Givol D, Yarden Y (1991). A specific combination of substrates is involved in signal transduction by the kitencoded receptor. EMBO J, 10, 647-54.
26	Kemmer K, Corless C, Fletcher C (2004). KIT mutations are common in testicular seminomas. Am J Pathol, 164, 30513.
27	Kindler T, Breitenbuecher F, Marx A (2004). The efficacy and safety of imatinib in adult patients with c-kit-positive acute myeloid leukemia. Blood, 103, 3644-54. DOI ScienceOn
28	Krystal GW, Hines SJ, Organ CP (1996). Autocrine growth of small cell lung cancer mediated by co-expression of c-KIT and stem cell factor. Cancer Res, 56, 370-6.
29	Lonardo F, Pass HI, Lucas DR (2003). Immunohistochemistry frequently detects c-KIT expression in pulmonary small cell carcinoma and may help select clinical subsets for a novel form of chemotherapy. Appl Immunohistochem Mol Morphol, 11, 51-5.
30	Longley BJ, Reguera MJ, Ma Y (2001). Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy. Leuk Res, 25, 571-6. DOI ScienceOn
31	Makhlouf HR, Remotti HE, Ishak KG (2002). Expression of KIT (CD117) in angiomyolipoma. Am J Surg Pathol, 26, 493-7. DOI ScienceOn
32	Mokhtar N, Gouda I, Adel I (2007). Cancer pathology registry 2003-2004 and time trend analysis; Ch. 3, 24-39.
33	Mostofi FK, SobinLH, Torloni H (1973). International histological typing of urinary bladder tumors. Geneva.
34	Natali PG, Nicotra MR, Sures I, et al (1992a). Expression of c-KIT receptor in normal and transformed human nonlymphoid tissues. Cancer Res, 52, 6139-43.
35	Aydin O, Yildiz L, Kefeli M, et al (2008). CD117 expression in normal,neoplastic, inflammatory, and reactive lesions of the thyroid. Pathology Res and Practice 204: 359-65. DOI ScienceOn
36	Demetri GD, von Mehren M, Blanke CD, et al (2002). Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med, 347, 472-80. DOI ScienceOn
37	Badr KM, Nolen JD, Derose PB, Cohen C (2004). Muscle invasive schistosomal squamous cell carcinoma of the urinary bladder: frequency and prognostic significance of p53, BCL-2, HER2/neu, and proliferation (MIB-1). Hum Pathol. 35 184-9. DOI ScienceOn
38	Blume-Jensen P, Claesson-Welsh L, Siegbahn A, et al (1991). Activation of the human c-KIT product by ligand-induced dimerization mediates circular actin reorganization and chemotaxis. EMBO J, 10, 4121-8.
39	Dawson B, Trapp R editors (2000). Basic and clinical biostatistics, 3rd ed. Oxford. London and Boston Lange Medical Books, 87-93.
40	DiPaola RS, Kuczynski WI, Onodera K, et al (1997). Evidence for a functional kit receptor in melanoma, breast, and lung carcinoma cells. Cancer Gene, 4, 176-82.
41	Elmore LW, Domson K, Moore JR, et al (2001). Expression of c-KIT (CD117) in benign and malignant human endometrial epithelium. Arch Pathol Lab Me, 125, 146-51.
42	Gambacorti-Passerini C (2008). Part I: Milestones in personalised medicine--imatinib. Lancet Oncology, 9, 600. DOI ScienceOn