Gurr Charlotte, Bamford Mark, Oswald Nicola, Udensi Louisa, Ready Christopher, Gupta Kritika, Buhagiar Tiffany, Saldanha Gerald
University of Leicester, Leicester, UK.
University Hospitals of Leicester NHS Trust, Leicester, UK.
Histopathology. 2025 Jan;86(2):226-235. doi: 10.1111/his.15300. Epub 2024 Aug 13.
Breslow thickness (BT) is the most important histological prognostic feature for melanoma prognosis, but it only captures tumour size in one dimension. Adding a further measurement in a different axis has been shown to improve prognostic value. It seems reasonable that further prognostic value could be obtained by estimating the number of invasive melanoma cells using nuclear count. The aim of this study was to show proof of concept that nuclear count has prognostic value independent of BT.
Melanoma cell nuclei were labelled with SRY-related HMG-box 10 (SOX10) protein, the sections scanned and StarDist machine-learning algorithm used to count nuclei in 102 cases of primary cutaneous melanoma. Prognostic value was assessed using survival analyses. Nuclear count correlated strongly with T category, BT and calculated tumour area (each P < 0.001), suggesting that it was a valid marker of melanoma burden. Nuclear count was a predictor for overall survival in univariable analysis [hazard ratio (HR) = 2.25, confidence interval (CI) = 1.66-3.06, P < 0.001] and multivariable analysis (HR = 2.60, CI = 1.59-4.24, P < 0.001). BT and ulceration were significant in univariable analyses, but not in multivariable models with nuclear count. Models containing nuclear count showed the best fit. Similar results were seen for melanoma-specific and metastasis-free survival. Nuclear count was able to stratify melanomas within a given T stage.
This study demonstrated proof of concept that counting melanoma nuclei may be an improved measure of invasive tumour burden compared to BT. Future studies will need to refine methods of nuclear detection and also to confirm its prognostic value.
Breslow厚度（BT）是黑色素瘤预后最重要的组织学预后特征，但它仅能反映肿瘤在一个维度上的大小。在不同轴向上增加进一步测量已被证明可提高预后价值。通过核计数估计侵袭性黑色素瘤细胞数量似乎可以获得进一步的预后价值。本研究的目的是证明核计数具有独立于BT的预后价值这一概念。
用SRY相关的HMG盒10（SOX10）蛋白标记黑色素瘤细胞核，扫描切片并使用StarDist机器学习算法对102例原发性皮肤黑色素瘤的细胞核进行计数。使用生存分析评估预后价值。核计数与T分期、BT和计算出的肿瘤面积密切相关（均P < 0.001），表明它是黑色素瘤负荷的有效标志物。在单变量分析中，核计数是总生存的预测因素[风险比（HR）= 2.25，置信区间（CI）= 1.66 - 3.06，P < 0.001]，在多变量分析中也是如此（HR = 2.60，CI = 1.59 - 4.24，P < 0.001）。BT和溃疡在单变量分析中具有显著性，但在包含核计数的多变量模型中则不然。包含核计数的模型拟合最佳。黑色素瘤特异性生存和无转移生存也得到了类似结果。核计数能够在给定的T分期内对黑色素瘤进行分层。
本研究证明了与BT相比，计数黑色素瘤细胞核可能是一种更好的侵袭性肿瘤负荷测量方法这一概念。未来的研究需要完善核检测方法，并确认其预后价值。
