Relationship between tumor-associated immune infiltrate and p16 staining over clinicopathological features in acral lentiginous melanoma

Clin Transl Oncol. 2019 Sep;21(9):1127-1134. doi: 10.1007/s12094-019-02033-x. Epub 2019 Feb 16.

Abstract

Purpose: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis.

Materials and methods: A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases.

Results: The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells.

Conclusions: Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .

Keywords: Acral melanoma; Macrophages; Prognosis Survival; Tumor-infiltrating lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Lentigo / immunology
  • Lentigo / metabolism
  • Lentigo / pathology*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Melanoma / immunology
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Prognosis
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16