New prognostic factors of cutaneous melanoma: a review of the literature

Li, N.; Mangini, Janine; Bhawan, Jag

doi:10.1034/j.1600-0560.2002.290602.x

Cited by 28 publications

(29 citation statements)

References 146 publications

(396 reference statements)

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“…Also, telomerase activity and microphthalmia-associated transcription factor (Mitf) are among new markers with potential prognostic value. 6,[10][11][12] Besides immunohistochemical markers, there is a variety of serological melanoma markers that are secreted to blood either directly by melanoma cells or as an indirect response of the patient's immune system. Mib-1, a proliferation marker, which recognizes the Ki-67 antigen, is expressed at increased levels both in primary and metastatic stages of melanoma.…”

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confidence: 99%

Ezrin in primary cutaneous melanoma

et al. 2005

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Ezrin is a member of the ezrin-radixin-moesin family of proteins that link the actin-containing cytoskeleton to the plasma membrane. Ezrin is also connected to signaling molecules involved in the regulation of cell survival, proliferation and migration. Here, we examined the expression of ezrin in 95 primary cutaneous melanomas and correlated ezrin expression with conventional prognostic factors and biomarkers. From 12 patients metastatic tissue samples were also examined. In addition to ezrin staining, Mib-1 proliferation antigen, p53 and Bcl-2 were evaluated. Ezrin immunoreactivity was seen in most tumors; only 19 (20%) melanomas were negative. A total of 48 (51%) tumors had weak immunoreactivity and 28 (29%) strong immunoreactivity. The intensity of ezrin immunoreactivity was associated with tumor thickness (Breslow, P ¼ 0.0008) and with tumor invasion level (Clark, P ¼ 0.004), thicker tumors having stronger immunoreactivity. Also, there was a correlation between higher Mib-1 index in tumors and strong ezrin expression. All metastatic samples (n ¼ 12) showed positive ezrin immunoreactivity. In univariate analysis of survival, patients (n ¼ 76) with positive ezrin immunoreactivity had worse clinical disease behavior than those (n ¼ 19) without ezrin immunoreactivity, but the difference was not significant (P ¼ 0.19). In multivariate analysis of survival, the ezrin immunoreactivity was not a significant marker. The results indicate that ezrin is expressed in most primary melanomas of the skin and in all metastatic tumors. Ezrin expression correlates with tumor thickness and level of invasion suggesting an association between ezrin expression and tumor progression.

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Ezrin in primary cutaneous melanoma

et al. 2005

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“…1 Tumor thickness, which is considered the best predictor of melanoma aggressiveness, is not always a reliable parameter and is not relevant for more advanced primary tumors and metastatic disease.…”

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Microtubule-Associated Protein 2, a Marker of Neuronal Differentiation, Induces Mitotic Defects, Inhibits Growth of Melanoma Cells, and Predicts Metastatic Potential of Cutaneous Melanoma

Soltani¹,

Pichardo²,

Song

et al. 2005

The American Journal of Pathology

161

112

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Dynamic instability of microtubules is critical for mitotic spindle assembly and disassembly during cell division, especially in rapidly dividing tumor cells. Microtubule-associated proteins (MAPs) are a family of proteins that influence this property. We showed previously that MAP2, a neuron-specific protein that stabilizes microtubules in the dendrites of postmitotic neurons, is induced in primary cutaneous melanoma but is absent in metastatic melanomas. We proposed that induction of a microtubule-stabilizing protein in primary melanoma could disrupt the dynamic instability of microtubules, inhibit cell division and prevent or delay tumor progression. Although a number of clinical and pathological factors that influence melanoma progression have been identified, to date there is no single histological, immunohistochemical, serological, or molecular marker that accurately predicts aggressive behavior of melanoma. 1 Tumor thickness, which is considered the best predictor of melanoma aggressiveness, is not always a reliable parameter and is not relevant for more advanced primary tumors and metastatic disease.1,2 Therefore, there is a need for identification of molecular markers that predict biological behavior of melanoma cells independent of tumor thickness.Melanoma exhibits plasticity of differentiation and is known to differentiate along multiple, including endothelial and neuronal, cellular pathways.3 However, the effects of transdifferentiation of melanoma cells on tumor progression are not well understood. Earlier, we showed that MAP2 (microtubule-associated protein 2), a neuronspecific protein, is expressed abundantly in early invasive primary melanoma lesions (by immunohistochemistry) and primary melanoma cell lines (by Northern and western blot analyses) but is absent in metastatic melanomas lesions and cell lines. 4 In addition to primary melanomas 5 expression of MAP2 has been reported in other cutaneous tumors with neuroendocrine differentia-

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“…For instance, widely used MART-1, HMB-45 and similar S100b cannot distinguish between benign melanocytic lesions and melanoma. 38,39 Moreover, MART-1 is not fully melanoma-specific, because it is also expressed in certain steroid-producing tumors, 43 and although the HMB-45 antibody, which was raised against an extract of melanoma cells, is thought to react against a sialylated glycoprotein (gp100), it may also react against other proteins. 44 Thus, a more specific melanoma biomarker would be a valuable addition to the pathologist's arsenal.…”

Section: Discussionmentioning

confidence: 99%

“…Like HMB-45, not only is MART-1 expressed in most, but not all, melanomas, it is also expressed in normal melanocytes and benign nevi. 38,39 Antibodies against HMB-45 and MART-1 stain this tumor with about the same intensity as TROY (Fig. 3c, panels 3 and 4, respectively) but, given the large number of studies on HMB-45 and MART-1 expression in melanoma, these markers were not further assessed here.…”

Section: Troy Is a Novel Retinoic Acid-regulated Gene In S91 Melanomamentioning

confidence: 99%

Tumor necrosis factor receptor superfamily member TROY is a novel melanoma biomarker and potential therapeutic target

Spanjaard

Whren

Graves

et al. 2006

Intl Journal of Cancer

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Incidence of melanoma continues to rise, and a better understanding of its genetics will be critical to improve diagnosis and develop new treatments. Here, we search for novel melanoma-specific genes that may serve as biomarkers and therapeutic targets by using an in vitro genetic screen. One identified cDNA encoded TROY, a member of the tumor necrosis factor receptor superfamily (TNFRSF). TROY is widely expressed during embryogenesis, but in adults expression is restricted to hair follicles and brain. However, TROY had never been associated with melanoma, and it was selected for further study. First we show that expression in melanoma is specific by semiquantitative RT-PCR analysis of a large panel of established tumor cell lines. Next, specificity of expression was evaluated by immunohistochemistry analysis of primary cell cultures and patient tissues. TROY is expressed in 2/2 primary melanoma cells and 45/45 melanoma tissue samples (p < 0.0001). With the exception of sebaceous glands, TROY is not expressed in normal skin biopsies (p < 0.0001) or primary skin cell cultures that contain keratinocytes and epidermal melanocytes, nor is it expressed in other skin tumor cells (p < 0.0001). Finally, we show that TROY regulates melanoma growth, because replication of melanoma cells with reduced TROY levels through treatment with short-interfering RNA was significantly decreased relative to control cells (p < 0.004). In summary, TROY is the first TNFRSF member that is a biomarker for melanoma. TROY also presents a potentially novel cell surface signaling target for inhibitors, cell and/or antibody-based immunotherapies. ' 2006 Wiley-Liss, Inc.

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New prognostic factors of cutaneous melanoma: a review of the literature

Cited by 28 publications

References 146 publications

Ezrin in primary cutaneous melanoma

Ezrin in primary cutaneous melanoma

Microtubule-Associated Protein 2, a Marker of Neuronal Differentiation, Induces Mitotic Defects, Inhibits Growth of Melanoma Cells, and Predicts Metastatic Potential of Cutaneous Melanoma

Tumor necrosis factor receptor superfamily member TROY is a novel melanoma biomarker and potential therapeutic target

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