Brożyna Anna A, Guo Huazhang, Yang Sun-Eun, Cornelius Lynn, Linette Gerald, Murphy Michael, Sheehan Christine, Ross Jeffrey, Slominski Andrzej, Carlson J Andrew
Department of Tumor Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Department of Tumor Pathology and Pathomorphology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Department of Pathology, University of Pittsburgh Medical Center, UPMC Cancer Pavilion, Pittsburgh, Pennsylvania.
J Cutan Pathol. 2017 Apr;44(4):328-337. doi: 10.1111/cup.12872. Epub 2017 Jan 26.
The expression of TRPM1 (melastatin) mRNA is an independent marker, as measured by radioactive in situ hybridization (RISH), of disease-free survival in primary cutaneous melanoma (PM). The aim of the study was to determine if chromogenic in situ hybridization (CISH) can reproduce results examining diagnostic and prognostic utility of TRPM1 mRNA expression in melanocytic proliferations as measured by RISH.
The expression of TRPM1 mRNA was detected by CISH in melanocytic nevi (MN, n = 61), PM (n = 145) and metastatic melanomas (MMs, n = 15).
A progressive loss of TRPM1 was found moving from MN to PM to MM. The histologic stepwise model of melanoma progression revealed that loss of TRPM1 occurred at the transition of RGP PM to VGP PM. As a diagnostic marker, TRPM1 gradient loss showed 93.8% sensitivity and 52.4% specificity for PM. Loss of TRPM1 mRNA correlated with melanoma aggressiveness markers and was independent predictor of disease-free and overall survival. The corresponding survival curves for degree of melanoma pigmentation matched those for degree of loss of TPRM1 mRNA.
Loss of TRPM1 mRNA expression appears to be a crucial event in the progression of melanoma to a more malignant, metastatic phenotype.
通过放射性原位杂交（RISH）检测，TRPM1（褪黑素）mRNA的表达是原发性皮肤黑色素瘤（PM）无病生存的独立标志物。本研究的目的是确定显色原位杂交（CISH）是否能够重现通过RISH检测TRPM1 mRNA表达在黑素细胞增殖中的诊断和预后效用的结果。
通过CISH检测黑素细胞痣（MN，n = 61）、PM（n = 145）和转移性黑色素瘤（MM，n = 15）中TRPM1 mRNA的表达。
从MN到PM再到MM，发现TRPM1逐渐缺失。黑色素瘤进展的组织学逐步模型显示，TRPM1的缺失发生在RGP PM向VGP PM的转变过程中。作为诊断标志物，TRPM1梯度缺失对PM的敏感性为93.8%，特异性为52.4%。TRPM1 mRNA的缺失与黑色素瘤侵袭性标志物相关，并且是无病生存和总生存的独立预测因子。黑色素瘤色素沉着程度的相应生存曲线与TPRM1 mRNA缺失程度的生存曲线相匹配。
TRPM1 mRNA表达的缺失似乎是黑色素瘤进展为更恶性、转移性表型的关键事件。
