title: Regenerating I messenger RNA and protein expression in the failing human testis: a potential molecular prognostic marker of seminoma.
abstract: Infertility has been stated as a risk factor for testicular cancer; but currently, there is no prognostic indicator of tumor development from the pathologic testis with impaired spermatogenesis. Regenerating proteins are expressed in many human tissues including the testis, and their role in carcinogenesis has been well documented. In the present work, regenerating I messenger RNA and protein expression and cellular protein localization were studied in testicular biopsies of patients with normal (obstructive azoospermia) or impaired spermatogenesis (nonobstructive azoospermia) and in seminoma testis by quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence analyses. No significant differences in regenerating I transcripts were reported between the 3 groups studied. However, regenerating I protein was highly expressed in pure seminoma and in placental-like alkaline phosphatase-positive seminiferous tubules with in situ carcinoma. Regenerating I protein levels measured by Western blotting increased from the placental-like alkaline phosphatase-negative distal region of the seminoma to the pure placental-like alkaline phosphatase-positive tumoral region. Importantly, although cells localized in seminiferous tubules of obstructive azoospermic patients with normal spermatogenesis were very slightly labeled, persisting germ, Sertoli, and myoid cells and fibrous tissues were strongly regenerating I positive in seminiferous tubules of nonobstructive azoospermia. These results suggest the possibility to use regenerating I as a prognostic marker of tumoral development in the infertile testis.
authors.affiliation: INSERM U 895, C3M, University of Nice Sophia Antipolis, 151 route Saint-Antoine de Ginestière, BP 2 3194, 06204 Nice, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Mauro
authors.forename: David H
authors.initials: DH
authors.lastname: Volle
authors.forename: Daniel
authors.initials: D
authors.lastname: Chevallier
authors.forename: Juliette
authors.initials: J
authors.lastname: Haudebourg
authors.forename: Françoise
authors.initials: F
authors.lastname: Sénégas-Balas
authors.forename: Georges
authors.initials: G
authors.lastname: Pointis
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051847:Lithostathine / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D018239:Seminoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013737:Testis / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051847:Lithostathine; C497617:REG1A protein, human; D012333:RNA, Messenger