Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers

Histopathology. 2005 Jun;46(6):622-34. doi: 10.1111/j.1365-2559.2005.02158.x.


Aims: To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers.

Methods and results: Clinical data and follow-up, histopathological features (pattern, cell size, thickness, mitoses, vascular invasion, lymphocytic infiltration) and immunohistochemical detection [CK20, thyroid transcription factor (TTF-1), chromogranin A, synaptophysin, p53, Ki67, Fli-1, CD99, c-Kit] were evaluated in 20 cases of MCC. Fli-1 and CD99 were detected in 90% and 55% of cases, respectively. Tumour size>30 mm, stage II, 'absent' lymphocytic infiltration, and the presence of>50% of Ki67+ tumour cells, were found to be prognostic indicators of disease-free interval (DFI), but only 'absent' lymphocytic infiltration constituted an independent prognostic factor of DFI after multivariate analysis. For overall survival, the same variables, together with local recurrence and lymph node involvement, had prognostic significance, with only local recurrence as an independent prognostic factor after multivariate analysis.

Conclusions: Absence of lymphocytic infiltration and Ki67 immunoreactivity in more than 50% of tumour cells should be evaluated in conjunction with other well-known prognostic markers in MCC. Furthermore, recognizing that Fli-1 and CD99 expression is commonly found in MCC by immunohistochemistry may avoid misinterpretation in the differential diagnosis of MCC with other small round cell tumours.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12E7 Antigen
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Merkel Cell / metabolism
  • Carcinoma, Merkel Cell / pathology*
  • Carcinoma, Merkel Cell / ultrastructure
  • Cell Adhesion Molecules / analysis
  • Chromogranin A
  • Chromogranins / analysis
  • DNA-Binding Proteins / analysis
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Intermediate Filament Proteins / analysis
  • Keratin-20
  • Ki-67 Antigen / analysis
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Nuclear Proteins / analysis
  • Prognosis
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-kit / analysis
  • Survival Analysis
  • Synaptophysin / analysis
  • Thyroid Nuclear Factor 1
  • Trans-Activators / analysis
  • Transcription Factors / analysis
  • Tumor Suppressor Protein p53 / analysis


  • 12E7 Antigen
  • Antigens, CD
  • Biomarkers, Tumor
  • CD99 protein, human
  • Cell Adhesion Molecules
  • Chromogranin A
  • Chromogranins
  • DNA-Binding Proteins
  • Intermediate Filament Proteins
  • KRT20 protein, human
  • Keratin-20
  • Ki-67 Antigen
  • NKX2-1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins
  • Synaptophysin
  • Thyroid Nuclear Factor 1
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-kit