title: Merkel cell carcinoma: mitoses, expression of Ki-67 and bcl-2 correlate with disease progression.
abstract: BACKGROUND
  There are conflicting data on markers of disease progression and outcome of Merkel cell carcinoma.
  
  
  OBJECTIVE
  We suggest to review histological and various immunohistochemical features of Merkel cell carcinoma specimens, in order to identify prognostic markers of clinical relevance.
  
  
  METHODS
  We collected paraffin-embedded blocks from primary tumours from 26 patients diagnosed with Merkel cell carcinoma and determined the following: type and size of the tumour, number of mitoses, proliferation rate (Ki-67 antibody), (anti)-apoptosis rate (bcl-2, p53, p63 antibodies) and lymphatic vessel invasion (D2-40 antibody for podoplanin). Two authors blinded to clinical outcome, independently assessed and scored all samples. The findings were correlated with tumour progression, which was determined by local recurrence, lymph node- or distant metastases.
  
  
  RESULTS
  During the average follow-up period of 63.4 months 12 (46%) patients had disease progression. Statistical analysis revealed Ki-67-staining (P = 0.005) as a marker of disease progression, high number of mitoses (P = 0.026) correlated with lymph node metastasis, while a tendency for increased Bcl-2 expression (P = 0.064) was found in patients with local recurrence. A higher number of invaded lymphatic capillaries showed a tendency in correlation with metastases (P = 0.072).
  
  
  CONCLUSIONS
  The findings indicate that high numbers of mitoses, proliferation and survival of tumour cells as marked by Ki-67- and Bcl-2-staining, and infiltration of lymphatic vessels, might correlate with the biological behaviour of Merkel cell carcinoma.
authors.affiliation: University of California San Francisco, San Francisco, CA, USA; Department of Dermatology, Rudolfstiftung Hospital, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Vujic
authors.forename: M
authors.initials: M
authors.lastname: Marker
authors.forename: C
authors.initials: C
authors.lastname: Posch
authors.forename: D
authors.initials: D
authors.lastname: Mühlehner
authors.forename: B
authors.initials: B
authors.lastname: Monshi
authors.forename: F
authors.initials: F
authors.lastname: Breier
authors.forename: A
authors.initials: A
authors.lastname: Steiner
authors.forename: S
authors.initials: S
authors.lastname: Ortiz-Urda
authors.forename: K
authors.initials: K
authors.lastname: Rappersberger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2