Ki-67, p53, and p16 expression, and G691S RET polymorphism in desmoplastic melanoma (DM): A clinicopathologic analysis of predictors of outcome

J Am Acad Dermatol. 2016 Sep;75(3):595-602. doi: 10.1016/j.jaad.2016.04.059.

Abstract

Background: The prognostic role Ki-67, p53, and p16 immunostains and RET (rearranged during transfection) polymorphism in desmoplastic melanoma has not been evaluated.

Objective: We sought to identify potential prognostic markers.

Methods: We performed Ki-67, p53, and p16 immunostains on 66 desmoplastic melanomas, and sequenced RET G691 polymorphism and recurrent mutations of 17 cancer genes in 55 and 20 cases, respectively.

Results: Recurrence and metastasis were documented in 11 of 66 (17%) and 26 of 66 (39%) patients, respectively. Death was noted in 25 of 55 (45%) patients. Ki-67 expression (≥10%, 43%) correlated with male gender (P = .009), ulceration (P = .002), and Breslow depth (P = .009). p53 Expression (≥50%, 28%) correlated with male gender (P = .002) and head and neck location (P = .0228). Using Kaplan-Meier plots, Ki-67 expression (P = .0425) and mitosis (P = .00295) correlated with overall survival, whereas vascular invasion (P = .0292) correlated with disease progression. There was a significant correlation between Ki-67 and p53 expression (P = .003). RET polymorphism was present in 10 of 46 (22%) cases and inversely correlated with Breslow depth (P = .024).

Limitation: Our study is small and lacks power to perform a multivariate analysis.

Conclusion: Although Ki-67 expression correlated with overall survival, additional studies are needed to determine whether Ki-67 would be an independent prognostic marker in addition to the current routine histopathologic assessment.

Keywords: Ki-67; RET polymorphism; desmoplastic melanoma; immunohistochemistry; p16; p57.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, p16
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / genetics*
  • Male
  • Melanoma / genetics*
  • Melanoma / mortality
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins c-ret / genetics
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Ki-67 Antigen
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-ret
  • RET protein, human