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Updated: Mar 22, 2026

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Ki-67 staining pattern as a prognostic biomarker for advanced acral melanoma
Marcel Arakaki Asato1, Isabeli Joaquim Contel2, Francisco Alves Moraes Neto3
1Faculty of Medicine, Universidade Federal do Mato Grosso do Sul, Campo Grande, MS, Brazil; Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil.
Background:
Acral cutaneous melanoma (ACM) is an aggressive skin cancer, especially when diagnosed in the advanced stage. The Ki-67 is a rapid tool for proliferation rate analysis. Previous data indicated that its staining pattern is distinct during the several stages of the cell cycle among epithelial cells.
Objective:
To evaluate the prognostic impact of Ki-67 expression pattern classification among advanced acral cutaneous melanoma cases.
Methods:
Two pathologists classified staining nuclear patterns of Ki-67 in the hot spot of scanning slides of advanced ACM (pT4): NP1 (randomly Ki-67 immunopositive fine or coarse granules), NP2 (Ki-67 stained in one or two well defined and centralized nodules), NP3 (Ki-67 seen as granules or nodules occupying most of the nucleus), NP4 (nucleoplasm with intense and homogeneous Ki-67 staining) and NP5 (empty central area with peripheral Ki-67). For analysis, seven cases per group ‒ Alive (Al) and Melanoma-Related Death (De) ‒ were randomly selected.
Results:
This pilot study analyzed 5676 Ki-67 positive nuclei. Means comparison between the two groups revealed differences in nuclear patterns NP1 (p = 0.0014), NP4 (p = 0.038), NP5 (p = 0.0193), and the total number of stained nuclei (p = 0.0258).
Study Limitations:
Small number of cases and biased value of 6.35 through the Bland-Altman analysis.
Conclusion:
The present analysis highlights the importance of Ki-67 staining patterns as a potential prognostic marker among ACM. High Ki-67 positive nuclei were associated with worse outcomes (death), particularly in staining patterns before and after mitosis (NP1, NP4, and NP5).

