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Stem cell factor as a novel diagnostic marker for early malignant germ cells

Stoop , H and Honecker, F and van de Geijn, G. J. M. and Gillis, A. J. M. and Cools, M. C. and de Boer, Meint J. and Bokemeyer, C and Wolffenbuttel, K. P. and Drop, S. L. S. and de Krijger, R. R. and Dennis, N and Summersgill, B and McIntyre, A and Shipley, J and Oosterhuis, J. W. and Looijenga, L. H. J. (2008) Stem cell factor as a novel diagnostic marker for early malignant germ cells. JOURNAL OF PATHOLOGY, 216 (1). pp. 43-54.

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Abstract

Carcinoma in situ (CIS) of the testis is the pre-invasive stage of type 11 testicular germ cell tumours (TGCTs) of adolescents and adults. These tumours are the most frequently diagnosed cancer in Caucasian adolescents and young adults. In dysgenetic gonads, the precursor of type II GCTs can be either CIS or a lesion known as gonadoblastoma (GB). CIS/GB originates from a primordial germ cell (PGC)/gonocyte, ie an embryonic cell. CIS can be cured by local low-dose irradiation, with limited side effects on hormonal function. Therefore, strategies for early diagnosis of CIS are essential. Various markers are informative to diagnose CIS in adult testis by immunohistochemistry, including c-KIT, PLAP, AP-2 gamma, NANOG, and POU5F1 (OCT3/4). OCT3/4 is the most informative and consistent in presence and expression level, resulting in intense nuclear staining. In the case of maturational delay of germ cells, frequently present in gonads of individuals at risk for type 11 (T)GCTs, use of these markers can result in overdiagnosis of malignant germ cells. This demonstrates the need for a more specific diagnostic marker to distinguish malignant germ cells from germ cells showing maturation delay. Here we report the novel finding that immunohistochemical detection of stem cell factor (SCF), the c-KIT ligand, is informative in this context. This was demonstrated in over 400 cases of normal (fetal, neonatal, infantile, and adult) and pathological gonads, as well as TGCT-derived cell lines, specifically in cases of CIS and GB. Both membrane-bound and soluble SCIF were expressed, suggestive of an autocrine loop. SCIF immunohistochemistry can be a valuable diagnostic tool, in addition to OCT3/4, to screen for precursor lesions of TGCTs, especially in patients with germ cell maturation delay. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Item Type:Article
Uncontrolled Keywords:stem cell factor; carcinoma in situ; gonadoblastoma; type II (testicular) germ cell tumours; OCT3/4; maturational delay; immunohistochemistry; diagnostic marker; primordial germ cells; pathogenesis
Subjects:Biomedical Science > Nanomedicine
ID Code:715
Deposited By:SPI
Deposited On:20 Jan 2009 10:33
Last Modified:26 Mar 2009 12:57

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