Detection of high‐mobility group proteins A1 and A2 represents a valid diagnostic marker in post‐pubertal testicular germ cell tumours

The high‐mobility group A (HMGA) non‐histone chromosomal proteins HMGA1 and HMGA2 are architectural factors. They are abundantly expressed during embryogenesis and in most malignant neoplasias, whereas their expression is low or absent in normal adult tissues. Their over‐expression is known to have a causal role in cellular neoplastic transformation. Previous studies from our group have shown that their expression is restricted to specific germinal cells. In this study we have evaluated, by immunohistochemistry, the expression of HMGA1 and HMGA2 in a series of post‐pubertal testicular tumours of different histological types, including 30 seminomas, 15 teratomas, 15 embryonal carcinomas and 10 mixed germinal tumours with a prominent yolk sac tumour component. HMGA1 protein expression was detected in all seminomas and embryonal carcinomas analysed, but not in teratomas or yolk sac carcinomas. Conversely, HMGA2 was present only in embryonal carcinomas and yolk sac carcinomas, but not in seminomas or teratomas. The immunohistochemical data were further confirmed by Western blot and, at the mRNA level, by RT–PCR analyses. These findings indicate that HMGA1 and HMGA2 are differently expressed with respect to the state of differentiation of testicular germ cell tumours (TGCTs), with over‐expression of both proteins in pluripotential embryonal carcinoma cells and loss of expression of HMGA1 in yolk sac tumours and of both proteins in the mature adult tissue of teratoma areas. Therefore, the different profiles of HMGA1 and HMGA2 protein expression could represent a valuable diagnostic tool in some cases in which the histological differential diagnosis is problematic. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[1]  P. Chieffi.  Molecular targets for the treatment of testicular germ cell tumors. , 2007, Mini reviews in medicinal chemistry.

[2]  A. Fusco,et al.  High-mobility group A1 inhibits p53 by cytoplasmic relocalization of its proapoptotic activator HIPK2. , 2007, The Journal of clinical investigation.

[3]  C. Croce,et al.  HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity. , 2006, Cancer cell.

[4]  G. Viglietto,et al.  Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell lymphomas , 2005, Oncogene.

[5]  T. Ulbright,et al.  Seminoma With Tubular, Microcystic, and Related Patterns: A Study of 28 Cases of Unusual Morphologic Variants That Often Cause Confusion With Yolk Sac Tumor , 2005, The American journal of surgical pathology.

[6]  L. Looijenga,et al.  Testicular germ-cell tumours in a broader perspective , 2005, Nature Reviews Cancer.

[7]  V. Reuter.  Origins and molecular biology of testicular germ cell tumors , 2005, Modern Pathology.

[8]  T. Ulbright.  Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues , 2005, Modern Pathology.

[9]  G. Mead,et al.  Diagnostic pitfalls in the histopathological diagnosis of testicular germ cell tumours , 2004 .

[10]  P. Chieffi,et al.  Phosphorylation of high-mobility group protein A2 by Nek2 kinase during the first meiotic division in mouse spermatocytes. , 2003, Molecular biology of the cell.

[11]  P. Chieffi,et al.  HMGA1 and HMGA2 protein expression in mouse spermatogenesis , 2002, Oncogene.

[12]  C. Croce,et al.  Role of the high mobility group A proteins in human lipomas. , 2001, Carcinogenesis.

[13]  T. Waldmann,et al.  Onset of natural killer cell lymphomas in transgenic mice carrying a truncated HMGI-C gene by the chronic stimulation of the IL-2 and IL-15 pathway , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  L. Resar,et al.  The oncogenic properties of the HMG-I gene family. , 2000, Cancer research.

[15]  G. Chiappetta,et al.  Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Croce,et al.  The expression of a truncated HMGI-C gene induces gigantism associated with lipomatosis. , 1999, Cancer research.

[17]  Xianjin Zhou,et al.  Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C , 1995, Nature.

[18]  M. Santoro,et al.  Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells , 1995, Molecular and cellular biology.

[19]  W. Travis,et al.  Metastatic mature teratoma in lung following testicular embryonal carcinoma and teratocarcinoma. , 1993, Archives of pathology & laboratory medicine.

[20]  Dimitris Thanos,et al.  The High Mobility Group protein HMG I(Y) is required for NF-κB-dependent virus induction of the human IFN-β gene , 1992, Cell.

[21]  R. Reeves,et al.  Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y , 1989, Molecular and cellular biology.