# Ki-67 staining pattern as a prognostic biomarker for advanced acral melanoma

## TL;DR

This study explores how Ki-67 staining patterns in advanced acral melanoma may predict patient outcomes, suggesting certain patterns are linked to worse survival.

## Contribution

The study introduces Ki-67 staining pattern classification as a novel prognostic tool for advanced acral melanoma.

## Key findings

- Ki-67 staining patterns NP1, NP4, and NP5 were associated with worse patient outcomes.
- Differences in nuclear patterns were statistically significant between survival groups.
- Higher Ki-67 positive nuclei correlated with melanoma-related death.

## Abstract

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.

To evaluate the prognostic impact of Ki-67 expression pattern classification among advanced acral cutaneous melanoma cases.

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.

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).

Small number of cases and biased value of 6.35 through the Bland-Altman analysis.

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).