TY - JOUR

T1 - CDH1 (E-cadherin) in testicular germ cell neoplasia: suppressed translation of mRNA in pre-invasive carcinoma in situ but increased protein levels in advanced tumours

AU - Sonne, Si B

AU - Hoei-Hansen, Christina E

AU - Nielsen, John E

AU - Herlihy, Amy S

AU - Andersson, Anna-Maria

AU - Almstrup, Kristian

AU - Daugaard, Gedske

AU - Skakkebaek, Niels E

AU - Leffers, Henrik

AU - Rajpert-De Meyts, Ewa

AU - Sonne, Si Brask

AU - Hoei-Hansen, Christina E

AU - Nielsen, John E

AU - Herlihy, Amy S

AU - Andersson, Anna-Maria

AU - Almstrup, Kristian

AU - Daugaard, Gedske

AU - Skakkebaek, Niels E

AU - Leffers, Henrik

AU - Rajpert-De Meyts, Ewa

N1 - Keywords: Adult; Animals; Cadherins; Carcinoma in Situ; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Precancerous Conditions; RNA, Messenger; Rabbits; Testicular Neoplasms

PY - 2006

Y1 - 2006

N2 - E-cadherin (CDH1) is a transmembrane glycoprotein involved in cellular adhesion. In our recent microarray studies of testicular germ cell tumours (TGCTs) and the common precursor carcinoma in situ (CIS), CDH1 mRNA was highly expressed in CIS and embryonal carcinoma. It has previously been reported that the CDH1 protein is not expressed in CIS. To resolve the discrepancy, we performed a detailed analysis of the expression of CDH1 mRNA and protein in a series of normal and neoplastic testes. High expression of CDH1 mRNA in CIS was confirmed by real-time PCR and in situ hybridisation. At the protein level, however, CDH1 was only detected with one of three tested antibodies, but Western blotting analysis with this antibody showed additional bands, suggesting unspecific staining. The levels of a CDH1 protein fragment in serum samples from 58 patients with TGCTs were analysed by ELISA; we found significantly higher levels in patients with advanced disease (stage II/III) when compared to healthy individuals and patients with stage I TGCT. In conclusion, despite high mRNA levels, the CDH1 protein is not expressed in CIS, suggesting translational suppression of CDH1 protein expression. CDH1 serum levels may be a serological marker for staging of TGCT patients.

AB - E-cadherin (CDH1) is a transmembrane glycoprotein involved in cellular adhesion. In our recent microarray studies of testicular germ cell tumours (TGCTs) and the common precursor carcinoma in situ (CIS), CDH1 mRNA was highly expressed in CIS and embryonal carcinoma. It has previously been reported that the CDH1 protein is not expressed in CIS. To resolve the discrepancy, we performed a detailed analysis of the expression of CDH1 mRNA and protein in a series of normal and neoplastic testes. High expression of CDH1 mRNA in CIS was confirmed by real-time PCR and in situ hybridisation. At the protein level, however, CDH1 was only detected with one of three tested antibodies, but Western blotting analysis with this antibody showed additional bands, suggesting unspecific staining. The levels of a CDH1 protein fragment in serum samples from 58 patients with TGCTs were analysed by ELISA; we found significantly higher levels in patients with advanced disease (stage II/III) when compared to healthy individuals and patients with stage I TGCT. In conclusion, despite high mRNA levels, the CDH1 protein is not expressed in CIS, suggesting translational suppression of CDH1 protein expression. CDH1 serum levels may be a serological marker for staging of TGCT patients.

U2 - 10.1111/j.1600-0463.2006.apm_445.x

DO - 10.1111/j.1600-0463.2006.apm_445.x

M3 - Journal article

C2 - 16907861

VL - 114

SP - 549

EP - 558

JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

SN - 0903-4641

IS - 7-8

ER -