Skip to main content
Log in

Heterogeneity of expression of immunohistochemical tumour markers in testicular carcinoma in situ: pathogenetic relevance

  • Original Articles
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Testicular carcinoma in situ (CIS) is the precursor of germ cell tumours in adults, except for spermatocytic seminoma. The mechanism of the progression from premalignant CIS to invasive and overt tumours is largely unknown. There are currently two main hypotheses: one is that CIS can progress directly to either seminoma or nonseminoma; according to the other, seminoma is the intermediate stage between CIS and nonseminoma. CIS cells express several tumour antigens, such as placental-like alkaline phosphatase (PLAP), TRA-1-60, or the c-kit proto-oncogene protein product (Kit), which are present to varying degrees in the invasive germ cell tumours. In this study, CIS cells adjacent to either pure or combined tumours were examined by double immunohistochemical staining for simultaneous expression of TRA-1-60 (typical for embryonal carcinoma) and either Kit (expressed by seminomas) or PLAP (found mainly in seminomas, but also in some cases of nonseminoma). Marked differences in the expression of these antigens were found among CIS cells, especially those adjacent to mixed tumours. We conclude that CIS is a phenotypically heterogeneous lesion, and that the CIS cells, despite identical morphology and close spatial localization, may be in different stages of progression. The results lend support to the hypothesis that CIS can progress directly to both seminomatous and nonseminomatous tumours.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Andrews PW, Banting GS, Damjanov I, Arnaud D, Avner P (1984) Three monoclonal antibodies defining distinct differentiation antigens associated with different high molecular weight polypeptides on the surface of human embryonal carcinoma cells. Hybridoma 3:347–361

    Google Scholar 

  2. Coffin CM, Ewing S, Dehner CP (1985) Frequency of intratubular germ cell neoplasia with invasive testicular germ cell tumors: histologic and immunocytochemical features. Arch Pathol Lab Med 109:555–559

    Google Scholar 

  3. Czaja J, Ulbright TM (1992) Evidence for the transformation of seminoma to yolk sac tumor, with histogenetic considerations. Am J Clin Pathol 97:468–477

    Google Scholar 

  4. Damjanov I (1989) Is seminoma a relative or a precursor of embryonal carcinoma? (Editorial). Lab Invest 60:1–3

    Google Scholar 

  5. Damjanov I (1991) Pathobiology of human germ cell neoplasia. Recent Results Cancer Res 123:1–16

    Google Scholar 

  6. Eble N (1994) Spermatocytic seminoma. Hum Pathol 25:1035–1042

    Google Scholar 

  7. Egan MJ, Crocker J (1992) Nucleolar organizer regions in pathology. Br J Cancer 65:1–7

    Google Scholar 

  8. Gillis AJ, Looijenga LH, Jong B de, Oosterhuis JW (1994) Clonality of combined testicular germ cell tumors of adults. Lab Invest 71:874–878

    Google Scholar 

  9. Giwercman A, Cantell L, Marks A (1991) Placental-like alkaline phosphatase as a marker of carcinoma-in-situ of the testis. Comparison with monoclonal antibodies M2A and 43–9F. APMIS 99:586–594

    Google Scholar 

  10. Giwercman A, Andrews PW, Jørgensen N, Müller J, Græm N, Skakkebæk NE (1993) Immunohistochemical expression of embryonal marker TRA-1–60 in carcinoma in situ and germ cell tumors of the testis. Cancer 72:1308–1314

    Google Scholar 

  11. Giwercman A, Lenz S, Skakkebæk NE (1993) Carcinoma in situ in atrophic testis: biopsy based on abnormal ultrasound pattern. Br J Urol 72:118–120

    Google Scholar 

  12. Graaf W de, Oosterhuis JW, Jong B de, Dam A, Putten WLJ van, Castedo SMMJ, Sleijfer DT, Schraffordt Koops H (1992) Ploidy of testicular carcinoma in situ. Lab Invest 66:166–168

    Google Scholar 

  13. Grégoire M, Schopperle WM, DeWolf CW (1995) Distinct glycoforms of a tumor specific glycoprotein, gp 200, in human testis and testicular tumors. J Urol 154:275–277

    Google Scholar 

  14. Grigor KM (1993) A new classification of germ cell tumours of the testis. Eur Urol 23:93–103

    Google Scholar 

  15. Gurp RJLM van, Oosterhuis JW, Kalscheuer V, Mariman ECM, Looijenga LHJ (1994) Human testicular germ cell tumours show biallelic expression of the H19 and IGF2 gene. J Natl Cancer Inst 86:1070–1077

    Google Scholar 

  16. Hofmann M-C, Jeltsch W, Brecher J, Walt H (1989) Alkaline phosphatase isozymes in human testicular germ cell tumors, their precancerous stage, and three related cell lines. Cancer Res 49:4696–4700

    Google Scholar 

  17. Jong B de, Oosterhuis JW, Castedo SMMJ, Vos AM, Meerman GJ te (1990) Pathogenesis of adult testicular germ cell tumors. A cytogenetic model. Cancer Genet Cytogenet 48:143–167

    Google Scholar 

  18. Jørgensen N, Rajpert-De Meyts E, Græm N, Müller J, Giwercman A, Skakkebæk NE (1995) Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells. Lab Invest 72:223–231

    Google Scholar 

  19. Krag Jacobsen G, Nørgaard-Pedersen B (1984) Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma-in-situ of the testis. APMIS 92:323–329

    Google Scholar 

  20. Looijenga LHJ (1994) Pathobiology of germ cell tumors of the adult testis; views and news. Doctoral thesis, Erasmus University Rotterdam

    Google Scholar 

  21. Looijenga LHJ, Gillis AJM, Putten WLJ van, Oosterhuis JW (1993) In situ numeric analysis of centromeric regions of chromosome 1, 12, 15 of seminomas, non-seminomatous germ cell tumors and carcinoma in situ of human testis. Lab Invest 68:211–219

    Google Scholar 

  22. Loy V, Dieckmann KP (1990) Carcinoma in situ of the testis: intratubular germ cell neoplasia or testicular intraepithelial neoplasia? Hum Pathol 21:457

    Google Scholar 

  23. Manivel JC, Jessurun J, Wick MR, Dehner LP (1987) Placental alkaline phosphatase immunoreactivity in testicular germ cell neoplasms. Am J Surg Pathol 11:21–29

    Google Scholar 

  24. Meng FJ, Giwercman A, Skakkebæk NE (1996) Quantification of argyrophylic nucleolar organizer region associated proteins (AgNORs) in the carcinoma-in-situ cell of the testis by computer-aided image analysis. J Pathol (Lond) (in press)

  25. Müller J, Skakkebæk NE, Lundsteen C (1981) Aneuploidy as a marker for carcinoma-in-situ of the testis. Acta Pathol Microbiol Scand [A] 89:67–68

    Google Scholar 

  26. Müller J, Skakkebæk NE, Constance Parkinson M (1987) The spermatocytic seminoma: views on pathogenesis. Int J Androl 10:147–156

    Google Scholar 

  27. Nistal M, Codesal J, Paniagua R (1989) Carcinoma in situ of the testis in infertile men. A histological, immunocytochemical, and cytomorphometric study of DNA content. J Pathol (Lond) 159:205–210

    Google Scholar 

  28. Oliver RTD (1987) HLA phenotype and clinicopathological behaviour of germ cell tumours: possible evidence for clonal evolution from seminomas to nonseminomas. Int J Androl 10:85–93

    Google Scholar 

  29. Oosterhuis JW, Castedo SMMJ, Jong B de, Cornelisse CJ, Dam A, Sleijfer DT, Schraffordt Koops H (1989) Ploidy of subtypes of primary germ cell tumors of the testis. Pathogenetic and clinical relevance. Lab Invest 60:14–21

    Google Scholar 

  30. Oosterhuis JW, Gillis AJM, Putten WLJ van, Jong B de, Looijenga LHJ (1993) Interphase cytogenetics of carcinoma in situ of the testis. Eur Urol 23:16–22

    Google Scholar 

  31. Pierce GB Jr, Abell MA (1970) Embryonal carcinoma of testes. Pathol Annu 5:27–60

    Google Scholar 

  32. Pugh RCB (ed) (1976) Pathology of the testis. Blackwell, Oxford London Edinburgh

    Google Scholar 

  33. Raghavan D, Sullivan AL, Peckham MJ, Neville AM (1982) Elevated serum alpha-fetoprotein and seminoma: clinical evidence for a histologic continuum? Cancer 50:982–989

    Google Scholar 

  34. Rajpert-De Meyts E, Skakkebæk NE (1994) Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours. Int J Androl 17:85–92

    Google Scholar 

  35. Skakkebæk NE (1972) Possible carcinoma-in-situ of the testis. Lancet II:516–517

    Google Scholar 

  36. Skakkebæk NE, Berthelsen JG (1981) Carcinoma-in-situ of the testis and invasive growth of different types of germ cell tumours. A revised germ cell theory. Int J Androl 4 [Suppl]:26–34

    Google Scholar 

  37. Skakkebæk NE, Berthelsen JG, Giwercman A, Müller J (1987) Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int J Androl 10:19–28

    Google Scholar 

  38. Srigley JR, Mackay B, Toth P, Ayala A (1988) The ultrastructure and histogenesis of male germ cell neoplasia with emphasis on seminoma with early carcinomatous features. Ultrastruct Pathol 12:67–86

    Google Scholar 

  39. Strohmeyer T, Peter S, Hartmann M, Munemitsu S, Ackermann R, Ullrich A, Slamon DJ (1991) Expression of the hst-1 and c-kit protooncogenes in human testicular germ cell tumors. Cancer Res 51:1811–1816

    Google Scholar 

  40. Treré D, Farabegoli F, Cancellieri A, Ceccarelli C, Eusebi V, Derenzini M (1991) AgNORs area in interphase nuclei of human tumours correlates with the proliferative activity evaluated by bromodeoxyuridine labelling and Ki-67 immunostaining. J Pathol (Lond) 165:53–59

    Google Scholar 

  41. Walt H, Arrenbrecht S, Delozier-Blanchet CD, Keller PJ, Nauer R, Hedinger CE (1986) A human testicular germ cell tumor with borderline histology between seminoma and embryonal carcinoma secreted beta-human chorionic gonadotropin and alpha-fetoprotein only as a xenograft. Cancer 58:139–146

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rajpert-De Meyts, E., Kvist, M. & Skakkebæk, N.E. Heterogeneity of expression of immunohistochemical tumour markers in testicular carcinoma in situ: pathogenetic relevance. Vichows Archiv A Pathol Anat 428, 133–139 (1996). https://doi.org/10.1007/BF00200655

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00200655

Key words

Navigation