Canine melanoma diagnosis: RACK1 as a potential biological marker

Vet Pathol. 2013 Nov;50(6):1083-90. doi: 10.1177/0300985813490754. Epub 2013 Jun 4.

Abstract

Melanoma diagnosis in dogs can be challenging due to the variety of histological appearances of canine melanocytic neoplasms. Markers of malignancy are needed. Receptor for activated C-kinase 1 (RACK1) was found to characterize melanomas in other mammals. We investigated the value of RACK1 detection in the classification of 19 cutaneous and 5 mucosal melanocytic neoplasms in dogs. These tumors were categorized as melanocytomas or benign and melanomas or malignant after evaluation of their morphology, mitotic index, and Ki-67 growth fraction. Using immunofluorescence, we confirmed microphthalmia-associated transcription factor (MITF) as a marker of normal and transformed melanocytic cells in dog tissues. All control (n = 10) and tumoral (n = 24) samples stained positively for MITF (34/34, 100%). Whereas RACK1 was not detected in healthy skin melanocytes, melanocytic lesions were all positive for RACK1 signal (24/24, 100%). RACK1 cytoplasmic staining appeared with 2 distinct distribution patterns: strong, diffuse, and homogeneous or granular and heterogeneous. All melanoma samples (13/13, 100%) stained homogeneously for RACK1. All melanocytomas (11/11, 100%) stained heterogeneously for RACK1. Immunohistochemistry was less consistent than immunofluorescence for all labelings in melanocytic lesions, which were often very pigmented. Thus, the fluorescent RACK1-MITF labeling pattern helped to distinguish melanomas from melanocytomas. Furthermore, RACK1 labeling correlated with 2 of 11 morphological features linked to malignancy: cell and nuclear size. These results suggest that RACK1 may be used as a marker in dog melanomas.

Keywords: MITF; RACK1; diagnosis; dog; immunofluorescence; melanocytoma; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Diagnosis, Differential
  • Dog Diseases / diagnosis*
  • Dog Diseases / metabolism
  • Dogs
  • Female
  • Immunohistochemistry / veterinary
  • Ki-67 Antigen / metabolism
  • Male
  • Melanocytes / metabolism
  • Melanocytes / pathology
  • Melanoma / diagnosis
  • Melanoma / metabolism
  • Melanoma / veterinary*
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface / metabolism*
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / veterinary*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface