Cytoplasmic expression of nm23 predicts the potential for cerebral metastasis in patients with primary cutaneous melanoma

Abstract

The nm23 gene is a putative tumour and metastasis suppressor gene. A number of studies have found that reduction of its expression is associated with increased metastatic potential in several human malignancies. Similarly, clinical studies have shown correlation between reduced nm23 protein expression and a poor prognosis. The aim of this study was to determine if a relationship exists between nm23 expression in primary cutaneous melanomas with or without cerebral metastases. Paraffin-embedded tissues were retrieved from 21 patients with primary cutaneous melanomas (n=21) and who subsequently developed cerebral metastases (n=24). Primary cutaneous melanomas with no regional or organ metastases within a 10 year period were used as control cases (n=34). Nm23 staining was localized in the cytoplasm of the tumour cells. Most of the control cases showed strong expression, whereas the majority of the primary melanomas with cerebral metastases showed no or weak expression of nm23. The cerebral metastases mostly showed strong expression. In summary, the results of this study may have significant prognostic implications for patients presenting with cutaneous melanoma. Patients with cutaneous melanomas with a low expression of nm23 appear to be more at risk of developing brain metastases.

NME1 (NME/NM23 nucleoside diphosphate kinase 1)

“…In lung carcinoma cell lines, increased NME1 expression (Nie et al, 2008) and NME1 silencing (Zhao et al, 2013) decreased invasion and increased TGFβ-induced epithelial mesenchymal transition, respectively. This correlation was also found by immunohistochemical studies (Lee et al, 1996;Sarris et al, 2004;Ferrari et al, 2007), one including more than 100 patients (McDermott et al, 2000). However, other studies, including fewer cases, concluded to a lack of correlation (Easty et al, 1996;Saitoh et al, 1996;van den Oord et al, 1997).…”

Metastasis: the seed and soil theory gains identity

“…Melanoma cells transfected with KiSS-1 showed significant decrease in metastatic ability [76]. Melanomas with low nm23 expression were highly predisposed to develop metastases to the brain, suggesting the predictive role of NM23 in tumor metastasis [77].…”

Tumor Dormancy and the Role of Metastasis Suppressor Genes In Regulating Ectopic Growth

“…In addition to experimental evidence demonstrating that downregulation of metastasis suppressor gene function correlates to increased metastatic burden [126,127,[171][172][173][174], there is growing clinical evidence that reduction in the expression of a metastasis suppressor gene can be linked to the presence of metastases [149,150,[174][175][176][177][178][179][180][181][182][183][184][185][186]. Furthermore, measurement of the expression of a metastasis suppressor gene may prove a useful indicator for monitoring the response to treatment [187][188][189].…”