title: Differential kinetic features by tumour topography in cutaneous small-cell neuroendocrine (Merkel cell) carcinomas.
abstract: OBJECTIVE
  Merkel cell carcinomas (MCC) reveal epithelial and neuroendocrine differentiation, but its topographic cell kinetics remains unknown. This study analyses proliferation, apoptosis, and DNA ploidy by topography, features that can help planning therapeutic protocols. This study topographically analyses proliferation, apoptosis, and DNA ploidy.
  
  
  METHODS
  We selected 27 small-cell MCCs (expressing one epithelial and two neural markers, with consistent ultrastructural findings) to evaluate mitotic figure counting, Ki-67 index, apoptosis index based on the in situ end labelling of fragmented DNA (using Escherichia coli DNA polymerase I, Klenow fragment), DNA ploidy, and BCL2 and TP53 immuno-expression. At least 50 high-power fields were screened per topographic compartment (superficial or papillary dermis, and deep or reticular dermis), recording average and standard deviation for each variable. Variables were statistically compared in each tumour compartment using analysis of variance and Student's t-test (significant if P < 0.05).
  
  
  RESULTS
  MCCs revealed superficial aneuploid DNA content, and no topographic differences for proliferation markers. Apoptosis showed significantly lower values in the deep compartment (average, P = 0.0050, and standard deviation, P = 0.0074), correlating with increased BCL2 and TP53 immuno-expressions.
  
  
  CONCLUSIONS
  High homogeneously distributed proliferation and superficial aneuploid DNA content defines MCCs. Apoptosis follows proliferation in superficial compartments, being less variable and proliferation independent in deep compartments, where it is inversely correlated with BCL2/TP53 expression.
authors: Department of Dermatology, Homerton University Hospital, London, UK.
authors: L
authors: L
authors: Pozo
authors: J J
authors: JJ
authors: Sanchez-Carrillo
authors: A
authors: A
authors: Martinez
authors: A
authors: A
authors: Blanes
authors: S J
authors: SJ
authors: Diaz-Cano
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D015266:Carcinoma, Merkel Cell / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D011003:Ploidies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D013194:Staining and Labeling; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53