Abstract
BackgroundGerm cell neoplasia in situ (GCNIS), is preinvasive stage of testicular germ cell tumours (TGCTs). Fibrillins, which are integral components of microfibrils are suggested to be involved in cancer pathogenesis and maintenance of embryonic stem cells pluripotency. The aim of this study was to examine fibrillin-1 (FBN-1) expression in TGCTs patients.MethodsSurgical specimens from 203 patients with TGCTs were included into the translational study. FBN-1 expression was evaluated in the tumour tissue, in GCNIS and in adjacent non-neoplastic testicular tissue in all available cases. Tissue samples were processed by the tissue microarray method. FBN-1 was detected by immunohistochemistry using goat polyclonal antibody and the expression was evaluated by the multiplicative quickscore (QS).ResultsThe highest FBN-1 positivity was detected in GCNIS (mean QS = 11.30), with overexpression of FBN-1 (QS >9) in the majority (77.1 %) of cases. Expression of FBN-1 in all subtypes of TGCTs was significantly lower in comparison to expression in GCNIS (all p <0.001). Seminoma had significantly higher expression compared to EC, ChC and TER (all p <0.05), but not to YST (p = 0.84). In non-neoplastic testicular tissue the FBN-1 positivity was very low (mean QS = 0.02). Sensitivity, specificity, positive and negative predictive value of FBN-1 expression for diagnosis of GCNIS were 97.1, 98.8, 98.6 and 97.7 %.ConclusionsFBN-1 is overexpressed in TGCTs and especially in GCNIS when compared to non-neoplastic testicular tissue in patients with germ cell tumors and could be involved in germ cell neoplasia in situ development.
Highlights
Germ cell neoplasia in situ (GCNIS), is preinvasive stage of testicular germ cell tumours (TGCTs)
Babal share last authorship. 22nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia 3Translational Research Unit, Faculty of Medicine, Comenius University, Bratislava, Slovakia Full list of author information is available at the end of the article (GCNIS) is a precursor lesion for invasive TGCTs of the adult testis [5] with the exceptions of prepubertal type teratomas which are rare in adults and spermatocytic tumours typical for elderly men and infantile germ cell tumours [6, 7]
Cancer cells in GCNIS as well as in TGCTs exhibit several similarities with embryonic stem cells; in this translational study we investigated expression of FBN-1 in patients with TGCTs
Summary
Germ cell neoplasia in situ (GCNIS), is preinvasive stage of testicular germ cell tumours (TGCTs). Germ cell neoplasia in situ (GCNIS) is a precursor lesion for invasive TGCTs of the adult testis [5] with the exceptions of prepubertal type teratomas which are rare in adults and spermatocytic tumours typical for elderly men and infantile germ cell tumours [6, 7]. GCNIS under term carcinoma in situ was first described in 1972 by Skakkebaek et al, in men who developed embryonal carcinoma of the testis, as atypical germ cells in seminiferous tubules suggested to represent a carcinoma in situ [8]. Germ cell neoplasia in situ is present adjacent to the invasive tumours in 72–98 % of the cases, in contralateral testis in 4.9–6.6 % of cases and sporadic finding in 0.4–0.8 % of the testes of otherwise healthy males [9]. If left untreated the risk of development of invasive testicular cancer is 70 % after 7 years [6]
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