nach oben

Virchows Archiv

Erschienen in:

01.12.2012 | Original Article

BMI1 expression identifies subtypes of Merkel cell carcinoma

verfasst von: Maria Kouzmina, Valtteri Häyry, Junnu Leikola, Caj Haglund, Tom Böhling, Virve Koljonen, Jaana Hagström

Erschienen in: Virchows Archiv | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

Abstract

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma. The aims of this study were to investigate the expression of the transcription factors B-lymphoma Moloney murine leukaemia virus insertion (BMI1), myelocytomatosis viral oncogene homologue (c-Myc) and Snail in MCC tumour specimens and to examine the relationship of these markers to Merkel cell polyoma virus (MCV). The study comprised of 133 patients with primary MCC. The expression of BMI1, Snail and c-Myc protein was assessed by immunohistochemistry and compared with clinical parameters, MCV status and patient survival. The presence of MCV was inversely correlated with the expression of BMI1 protein. Tumours expressing BMI1 protein more often presented with lymph node metastases. Snail protein expression was decreased in cases with metastatic dissemination. This study identified two subgroups of MCC: tumours expressing BMI1 but negative for MCV DNA and tumours negative for BMI1 expression but positive for MCV. Importantly, BMI1-positive cases often presented with lymph node metastases. Combined, these results suggest that subtypes of this malignancy exist.

Szeder V, Grim M, Kucera J et al (2003) Neurotrophin-3 signaling in mammalian Merkel cell development. Dev Dyn 228:623–629PubMedCrossRef

Lucarz A, Brand G (2007) Current considerations about Merkel cells. Eur J Cell Biol 86:243–251PubMedCrossRef

Winkelmann RK (1977) The Merkel cell system and a comparison between it and the neurosecretory or APUD cell system. J Invest Dermatol 69:41–46PubMedCrossRef

Grim M, Halata Z (2000) Developmental origin of avian Merkel cells. Anat Embryol (Berl) 202:401–410CrossRef

Sidhu GS, Chandra P, Cassai ND (2005) Merkel cells, normal and neoplastic: an update. Ultrastruct Pathol 29:287–294PubMedCrossRef

Compton CC, Regauer S, Seiler GR et al (1990) Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts. Lab Invest 63:233–241PubMed

Brown JA, Smoller BR (2009) Merkel cell carcinoma: what is it, what will it do and where will it go? What role should the pathologist play in reporting this information? J Cutan Pathol 36:924–927PubMedCrossRef

Calder KB, Smoller BR (2010) New insights into Merkel cell carcinoma. Adv Anat Pathol 17:155–161. doi:10.1097/PAP.0b013e3181d97836 PubMedCrossRef

Hwang JH, Alanen K, Dabbs KD et al (2008) Merkel cell carcinoma with squamous and sarcomatous differentiation. J Cutan Pathol 35:955–959PubMedCrossRef

10.

Saeb-Lima M, Montante-Montes de Oca D, Albores-Saavedra J (2008) Merkel cell carcinoma with eccrine differentiation: a clinicopathologic study of 7 cases. Ann Diagn Pathol 12:410–414PubMedCrossRef

11.

Cooper L, Debono R, Alsanjari N et al (2000) Merkel cell tumour with leiomyosarcomatous differentiation. Histopathology 36:540–543PubMedCrossRef

12.

Eusebi V, Damiani S, Pasquinelli G et al (2000) Small cell neuroendocrine carcinoma with skeletal muscle differentiation: report of three cases. Am J Surg Pathol 24:223–230PubMedCrossRef

13.

Tan KB, Murali R, Karim RZ et al (2008) Merkel cell carcinoma with fibrosarcomatous differentiation. Pathology 40:314–316PubMedCrossRef

14.

Van Keymeulen A, Mascre G, Youseff KK et al (2009) Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol 187(1):91–100PubMedCrossRef

15.

Vaigot P, Pisani A, Darmon YM et al (1987) The majority of epidermal Merkel cells are non-proliferative: a quantitative immunofluorescence analysis. Acta Derm Venereol 67:517–520PubMed

16.

Moll I, Zieger W, Schmelz M (1996) Proliferative Merkel cells were not detected in human skin. Arch Dermatol Res 288:184–187PubMedCrossRef

17.

Ezeh UI, Turek PJ, Reijo RA et al (2005) Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer 104:2255–2265. doi:10.1002/cncr.21432 PubMedCrossRef

18.

Monk M, Holding C (2001) Human embryonic genes re-expressed in cancer cells. Oncogene 20:8085–8091. doi:10.1038/sj.onc.1205088 PubMedCrossRef

19.

Al-Hajj M (2007) Cancer stem cells and oncology therapeutics. Curr Opin Oncol 19:61–64. doi:10.1097/CCO.0b013e328011a8d6 PubMed

20.

Ailles LE, Weissman IL (2007) Cancer stem cells in solid tumors. Curr Opin Biotechnol 18:460–466. doi:10.1016/j.copbio.2007.10.007 PubMedCrossRef

21.

Abbas O, Bhawan J (2011) Expression of stem cell markers nestin and cytokeratin 15 and 19 in cutaneous malignancies. J Eur Acad Dermatol Venereol 25:311–316. doi:10.1111/j.1468-3083.2010.03791.x PubMedCrossRef

22.

Leung C, Lingbeek M, Shakhova O et al (2004) Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428:337–341. doi:10.1038/nature02385 PubMedCrossRef

23.

Mihic-Probst D, Kuster A, Kilgus S et al (2007) Consistent expression of the stem cell renewal factor BMI-1 in primary and metastatic melanoma. Int J Cancer 121:1764–1770. doi:10.1002/ijc.22891 PubMedCrossRef

24.

Bracken AP, Dietrich N, Pasini D et al (2006) Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev 20:1123–1136. doi:10.1101/gad.381706 PubMedCrossRef

25.

Ambler CA, Maatta A (2009) Epidermal stem cells: location, potential and contribution to cancer. J Pathol 217:206–216. doi:10.1002/path.2468 PubMedCrossRef

26.

Guney I, Wu S, Sedivy JM (2006) Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16(INK4a). Proc Natl Acad Sci U S A 103:3645–3650. doi:10.1073/pnas.0600069103 PubMedCrossRef

27.

Nakamura M, Tokura Y (2011) Epithelial–mesenchymal transition in the skin. J Dermatol Sci 61:7–13. doi:10.1016/j.jdermsci.2010.11.015 PubMedCrossRef

28.

Feng H, Shuda M, Chang Y et al (2008) Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319:1096–1100PubMedCrossRef

29.

Foulongne V, Kluger N, Dereure O et al (2008) Merkel cell polyomavirus and Merkel cell carcinoma, France. Emerg Infect Dis 14:1491–1493PubMedCrossRef

30.

Becker JC, Houben R, Ugurel S et al (2009) MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol 129:248–250PubMedCrossRef

31.

Sihto H, Kukko H, Koljonen V et al (2009) Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma. J Natl Cancer Inst 101:938–945PubMedCrossRef

32.

Garneski KM, Warcola AH, Feng Q et al (2009) Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol 129:246–248PubMedCrossRef

33.

Shuda M, Feng H, Kwun HJ et al (2008) T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci U S A 105:16272–16277PubMedCrossRef

34.

Alison MR, Lim SM, Nicholson LJ (2011) Cancer stem cells: problems for therapy? J Pathol 223:147–161. doi:10.1002/path.2793 PubMedCrossRef

35.

Edge SB, Byrd DR, Compton CC (eds) (2010) Merkel cell carcinoma. Springer, New York, pp 315–323

36.

Brunner M, Thurnher D, Pammer J et al (2008) Expression of VEGF-A/C, VEGF-R2, PDGF-alpha/beta, c-kit, EGFR, Her-2/Neu, Mcl-1 and Bmi-1 in Merkel cell carcinoma. Mod Pathol 21:876–884PubMedCrossRef

37.

Haga K, Ohno S, Yugawa T et al (2007) Efficient immortalization of primary human cells by p16INK4a-specific short hairpin RNA or Bmi-1, combined with introduction of hTERT. Cancer Sci 98:147–154. doi:10.1111/j.1349-7006.2006.00373.x PubMedCrossRef

38.

Bachmann IM, Puntervoll HE, Otte AP et al (2008) Loss of BMI-1 expression is associated with clinical progress of malignant melanoma. Mod Pathol 21:583–590. doi:10.1038/modpathol.2008.17 PubMedCrossRef

39.

Reinisch CM, Uthman A, Erovic BM et al (2007) Expression of BMI-1 in normal skin and inflammatory and neoplastic skin lesions. J Cutan Pathol 34:174–180. doi:10.1111/j.1600-0560.2006.00587.x PubMedCrossRef

40.

Miller RW, Rabkin CS (1999) Merkel cell carcinoma and melanoma: etiological similarities and differences. Cancer Epidemiol Biomarkers Prev 8:153–158PubMed

41.

Tai PT, Yu E, Winquist E et al (2000) Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. J Clin Oncol 18:2493–2499PubMed

42.

Li J, Gong LY, Song LB et al (2010) Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-kappaB pathway. Am J Pathol 176:699–709. doi:10.2353/ajpath.2010.090502 PubMedCrossRef

43.

Lee K, Adhikary G, Balasubramanian S et al (2008) Expression of Bmi-1 in epidermis enhances cell survival by altering cell cycle regulatory protein expression and inhibiting apoptosis. J Invest Dermatol 128:9–17. doi:10.1038/sj.jid.5700949 PubMedCrossRef

44.

Cohen KJ, Hanna JS, Prescott JE et al (1996) Transformation by the Bmi-1 oncoprotein correlates with its subnuclear localization but not its transcriptional suppression activity. Mol Cell Biol 16:5527–5535PubMed

45.

Becker KF, Rosivatz E, Blechschmidt K et al (2007) Analysis of the E-cadherin repressor Snail in primary human cancers. Cells Tissues Organs 185:204–212. doi:10.1159/000101321 PubMedCrossRef

Titel: BMI1 expression identifies subtypes of Merkel cell carcinoma
verfasst von: Maria Kouzmina
Valtteri Häyry
Junnu Leikola
Caj Haglund
Tom Böhling
Virve Koljonen
Jaana Hagström
Publikationsdatum: 01.12.2012
Verlag: Springer-Verlag
Erschienen in: Virchows Archiv / Ausgabe 6/2012
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-012-1327-7

Springer Medizin

BMI1 expression identifies subtypes of Merkel cell carcinoma

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2012

Bilateral Sertoli cell tumors of the testis—a likely new extracolonic manifestation of familial adenomatous polyposis

The presence of sinusoidal CD163+ macrophages in lymph nodes is associated with favorable nodal status in patients with breast cancer

MicroRNA expression profiles of seminoma from paraffin-embedded formalin-fixed tissue

Metastasis of endometrial adenocarcinoma in a primary lung adenocarcinoma

Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma

Histological characteristics of the human femoral head in patients with femoral neck fracture

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie