Canine cutaneous melanocytic tumours: significance of β-catenin and survivin immunohistochemical expression

Vet Dermatol. 2015 Aug;26(4):270-e59. doi: 10.1111/vde.12211. Epub 2015 May 12.

Abstract

Background: Recent investigations have highlighted the controversial role of Wnt/β-catenin pathway activation in human cutaneous melanoma. Survivin has been proposed as a valid prognostic marker for invasive and metastatic melanomas and lymph node melanoma metastasis in human cutaneous melanoma and is a promising therapeutic target.

Hypothesis/objectives: Our aim was to investigate the immunohistochemical expression of survivin and β-catenin in canine cutaneous melanocytic tumours, in order to understand their prognostic significance.

Methods: Twenty-one melanocytic tumours (10 melanocytomas and 11 melanomas) were investigated by immunohistochemistry using specific anti-survivin and anti-β-catenin antibodies. A semi-quantitative method was used to analyse the results; β-catenin immunolabelling in neoplastic cells was evaluated as cytoplasmic, membranous or nuclear. The number of survivin-positive cells was counted within ~1000 neoplastic cells. Results were related to histopathological features, evaluated in haematoxylin- and eosin-stained slides, and to the clinical data obtained through a telephone survey with referring veterinarians.

Results: Despite a low level of expression in the majority of cases, β-catenin was found to be correlated strongly with malignant behaviour (P < 0.01). An overexpression of nuclear survivin was statistically related to histological features of malignancy, presence of metastasis and death related to melanoma spread (P < 0.01).

Conclusions and clinical importance: The low nuclear β-catenin expression, mainly found in metastatic cases, would indicate that β-catenin activation may have only limited importance in the development or progression of canine cutaneous melanoma. The correlation of nuclear survivin expression with malignancy would indicate that survivin is possibly a useful prognostic marker and therapeutic target in canine melanoma patients.

MeSH terms

  • Animals
  • Dog Diseases / pathology*
  • Dogs
  • Female
  • Male
  • Melanoma / pathology
  • Melanoma / veterinary*
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism*
  • Retrospective Studies
  • Skin / pathology
  • Skin Neoplasms / pathology
  • Skin Neoplasms / veterinary*
  • beta Catenin / metabolism*

Substances

  • Neoplasm Proteins
  • beta Catenin