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 .
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Acknowledgements
This study was possible thanks to the use of the Automatic Multispectral Imaging System (Olympus BX63) financed by the Programa Nacional de Innovación para la Competitividad y Productividad (Innovate Peru), under the contract 317-PNICP-EC-2014.
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Castaneda, C.A., Castillo, M., Torres-Cabala, C. et al. Relationship between tumor-associated immune infiltrate and p16 staining over clinicopathological features in acral lentiginous melanoma. Clin Transl Oncol 21, 1127–1134 (2019). https://doi.org/10.1007/s12094-019-02033-x
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DOI: https://doi.org/10.1007/s12094-019-02033-x