Mode of c‐myc protein expression in Spitz nevi, common melanocytic nevi and malignant melanomas

Bergman, Reuven; Lurie, M.; Kerner, Hedviga; Kilim, Sigalit; Friedman‐Birnbaum, Rachel

doi:10.1111/j.1600-0560.1997.tb01584.x

Cited by 18 publications

(12 citation statements)

References 17 publications

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“…Our results both on RNA and protein level confirm published data showing similar cmyc expression on the protein level in primary melanoma and in nevi (Bergman et al, 1997) and a higher expression in melanoma metastases (Grover et al, 1996). Regarding the relation of c-myc expression to the number of c-myc FISH signals, nevi and a subset of primary tumours with a tumour thickness up to 1.04 mm have both a combination of low expression and low signal number, whereas primary melanomas with a high tumour thickness (5.2 mm; 11.0 mm; 12.1 mm) have either an elevated expression or a higher number of signals (Table 2, Figure 5).…”

Section: Discussionsupporting

confidence: 92%

Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases

et al. 2001

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Summary Amplification and overexpression of the c-myc gene have been associated with neoplastic transformation in a plethora of malignant tumours. We applied interphase fluorescence in situ hybridization (FISH) with a locus-specific probe for the c-myc gene (8q24) in combination with a corresponding chromosome 8 α-satellite probe to evaluate genetic alterations in 8 primary melanomas and 33 advanced melanomas and compared it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin. Additionally, in metaphase spreads of 7 melanoma cell lines a whole chromosome 8 paint probe was used. We investigated the functionality of the c-myc gene by detecting c-myc RNA expression with RT-PCR and c-myc protein by immunohistochemistry. 4/8 primary melanomas and 11/33 melanoma metastases showed additional c-myc signals relative to the centromere of chromosome 8 copy number. None of the nevi, safety margins or normal skin samples demonstrated this gain. In 2/7 melanoma cell lines (C32 and WM 266-4) isochromosome 8q formation with a relative gain of c-myc copies and a loss of 8p was observed. The highest c-myc gene expression compared to GAPDH was found in melanoma metastases (17.5%). Nevi (6.6%) and primary melanomas (5.0%) expressed the c-myc gene on a lower level. 72.7% of the patients with c-myc extra copies had visceral melanoma metastases (UICC IV), patients without c-myc gain in 35.0% only. The collective with additional c-myc copies also expressed the gene on a significantly higher level. These results indicate that a c-myc gain in relation to the centromere 8 copy number might be associated with advanced cutaneous melanoma.

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Section: Discussionsupporting

confidence: 92%

Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases

et al. 2001

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“…Given these data and the fact that human benign nevi contain senescent melanocytes (3, 12, 13), we were surprised by previous reports suggesting that human nevi express proliferation-promoting Wnt targets, such as cyclin D1, c-myc, and MITF (40)(41)(42). However, we confirmed that many melanocytic nests of human benign nevi exhibited coincident expression of nuclear β-catenin and its proliferation-promoting targets, cyclin D1 and c-myc (Fig.…”

Section: Resultscontrasting

confidence: 44%

Wnt signaling potentiates nevogenesis

Pawlikowski

McBryan

Tuyn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway (senescence-associated secretory phenotype). Cellular senescence is also a tumor suppressor mechanism, to which both proliferation arrest and senescence-associated secretory phenotype are thought to contribute. The melanocytes within benign human nevi are a paradigm for tumor-suppressive senescent cells in a premalignant neoplasm. Here a comparison of proliferating and senescent melanocytes and melanoma cell lines by RNA sequencing emphasizes the importance of senescenceassociated proliferation arrest in suppression of transformation. Previous studies showed that activation of the Wnt signaling pathway can delay or bypass senescence. Consistent with this, we present evidence that repression of Wnt signaling contributes to melanocyte senescence in vitro. Surprisingly, Wnt signaling is active in many senescent human melanocytes in nevi, and this is linked to histological indicators of higher proliferative and malignant potential. In a mouse, activated Wnt signaling delays senescenceassociated proliferation arrest to expand the population of senescent oncogene-expressing melanocytes. These results suggest that Wnt signaling can potentiate nevogenesis in vivo by delaying senescence. Further, we suggest that activated Wnt signaling in human nevi undermines senescence-mediated tumor suppression and enhances the probability of malignancy.

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“…Thus, neither HMB-45, AgNOR, cyclin D1, c-myc, c-fos, telomerase, cdc-7, anti-leptin receptor, BCL-2, p53 nor p16 proved helpfulness in distinguishing Spitz nevi from melanoma. 13,[24][25][26][27][28][29][30][31][32][33] In this study, we performed a comparative analysis of protein expression using a wide panel of antibodies between classical Spitz nevi and vertical growth phase melanomas. Using tissue microarray analysis, a high-throughput means that allows the evaluation of several markers in a large number of melanocytic tumors, we identified a specific protein expression profile differentiating between typical Spitz nevus and non-spitzoid melanoma (Table 2).…”

Section: Discussionmentioning

confidence: 99%

The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study

et al. 2010

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Several isolated markers have been proposed to aid in differential diagnostic of difficult melanocytic lesions, albeit none has been shown to be definitive in differentiating Spitz nevus from melanoma. This study proposes a wide panel of 22 markers having important functions in different biological functions (cell cycle, apoptosis, DNA repair proteins and membranous receptors) to provide a combination of proteins associated with either benign or malignant phenotype. Using tissue microarrays, we compared protein expression profiles in 28 typical Spitz nevi and 62 primary vertical growth phase non-spitzoid melanomas. Most of the significant differences were linked to cell-cycle deregulation such as overexpression of cyclin D1 and p21 in Spitz nevi compared with non-spitzoid melanomas (74 vs 16% and 91 vs 27%, respectively) and mitotic rate including Ki-67, highly expressed in deep areas of non-spitzoid melanomas (37%), whereas it is not expressed in Spitz nevi (0%), topoisomerase IIa (79% in non-spitzoid melanomas vs 15% in Spitz nevi) and nuclear survivin (69% in melanomas vs 0% in Spitz nevi). A combination of biological markers differentially expressed in Spitz nevi from non-spitzoid melanomas is defined, thus providing a potential tool for histopathological differential diagnostic between Spitz nevus and melanoma. Nevertheless, more studies including atypical Spitz nevi and spitzoid melanomas are necessary to further establish a reliable panel to differentiate among difficult cases.

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Mode of c‐myc protein expression in Spitz nevi, common melanocytic nevi and malignant melanomas

Cited by 18 publications

References 17 publications

Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases

Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases

Wnt signaling potentiates nevogenesis

The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study

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