Expression of the embryonic morphogen Nodal in cutaneous melanocytic lesions

Abstract

Nodal, a potent embryonic morphogen in the transforming growth factor-b family, is a proposed key regulator of melanoma tumorigenicity. However, there has been no systematic study of Nodal expression in melanocytic lesions. We investigated Nodal expression by immunohistochemistry in 269 melanocytic lesions, including compound nevi, dysplastic nevi, congenital nevi, Spitz nevi, melanoma in situ, malignant melanoma including the variant desmoplastic melanoma, and metastatic melanoma. We found that the Nodal expression was significantly increased in malignant lesions (including melanoma in situ, malignant melanoma, and metastatic melanoma) compared with compound nevi, Spitz nevi, and dysplastic nevi. Surprisingly, congenital nevi expressed a level of Nodal comparable with malignant lesions, whereas desmoplastic melanoma showed lower expression than nondesmoplastic malignant melanoma (Po0.05). Deep melanoma (Breslow depth 41 mm) displayed a higher percentage of Nodal-positive tumor cells than did superficial melanoma (Breslow depth r1 mm), although there was no statistical difference in the overall staining intensity (P ¼ 0.18). Melanomas in situ showed a lower level of Nodal expression than did deep melanomas and metastatic melanomas (Po0.05). The low expression of Nodal in normal and dysplastic nevi, and its increasing expression with the progression of malignant lesions, are suggestive of a role for Nodal in melanoma progression.

Melanoma Tumor Cell Heterogeneity: A Molecular Approach to Study Subpopulations Expressing the Embryonic Morphogen Nodal

“…9–10,14 Similar observations have been reported in gliomas and carcinomas of the breast, prostate, endometrium, liver and pancreas. 15–20 However, with any new discovery, there are associated challenges.…”

Nodal expression in triple-negative breast cancer: Cellular effects of its inhibition following doxorubicin treatment

“…These data indicate that higher levels of Nodal are found within TNBC even when compared to invasive receptor positive tumors (summarized in Table 1), and are in agreement with studies that have reported correlations with Nodal expression and aggressive cancer-related characteristics. 13,15,[18][19][20][21][22][23] Collectively, our results demonstrate the robust presence of Nodal in TNBC samples, representing a potential new target for this disease.…”

Expression of the embryonic morphogen Nodal in differentiated thyroid carcinomas: Immunohistochemistry assay in tissue microarray and The Cancer Genome Atlas data analysis

“…This binding leads to the activation and nuclear translocation of the Smad 2/3/4 complex, which regulates the expression of genes involved in stem cell maintenance and cellular plasticity as well as inducing the expression of Nodal itself. 15,16 In addition, immunohistochemic studies of melanocytic tumors show that Nodal expression is associated with the progression of malignant lesions, 17 and Lawrence et al 11 reported that Nodal was overexpressed in cancer tissues and that Nodal enhances the growth of prostate cancer cells. Notch signaling is necessary for Nodal expression during embryo development.…”