Cdc7 expression in melanomas, Spitz tumors and melanocytic nevi

Clarke, Loren E.; Fountaine, Thomas J.; Hennessy, Jeannie; Bruggeman, Richard; Clarke, Jennie T.; Mauger, David T.; Helm, Klaus F.

doi:10.1111/j.1600-0560.2008.01077.x

Cited by 28 publications

(21 citation statements)

References 15 publications

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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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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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“…In one study, Bonte et al [14] analyzed a total of 35 tissue samples from breast, colon, and lung cancers and found strong Cdc7 expression in 71% of these tumors. Clarke et al [15] reported significantly higher Cdc7 expression levels in 40 melanomas as compared to 40 Spitz tumors and 30 nevi. Only recently, Kulkarni et al [16] analyzed 143 ovarian cancers and linked Cdc7 expression to high grade and advanced tumors and patient prognosis.…”

Section: Introductionmentioning

confidence: 98%

Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer

et al. 2010

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“…The greatest discriminatory effect of Cdc7 expression was observed for stage 3 and 4 ovarian tumors, which make up the vast majority of epithelial ovarian carcinoma cases (35). Cdc7 and Dbf4 are overexpressed in malignant melanoma compared with benign melanocytic nevi, and Dbf4 overexpression has been associated with lower relapse-free survival (36,37). In diffuse large B-cell lymphoma, increased Cdc7 activity is associated with poor clinical outcome (38).…”

Section: Cell Division Cycle 7 Overexpressionmentioning

confidence: 99%

Targeting Cell Division Cycle 7 Kinase: A New Approach for Cancer Therapy

Montagnoli

Moll

Colotta

2010

Clinical Cancer Research

104

107

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The cell division cycle 7 (Cdc7) is a serine-threonine kinase, originally discovered in budding yeast, required to initiate DNA replication. Human Cdc7 phosphorylates the minichromosome maintenance protein 2 (Mcm2), a component of the DNA replicative helicase needed for genome duplication. Inhibition of Cdc7 in cancer cells impairs progression through S phase, inducing a p53-independent apoptotic cell death, whereas in normal cells, it does not affect cell viability. Small molecule compounds able to interfere with Cdc7 activity have been identified and shown to be effective in controlling tumor growth in animal models. Two Cdc7 inhibitors are currently in phase I clinical development. Inhibition of Cdc7 kinase activity in cancer cells restricts DNA replication and induces apoptotic cell death by an unprecedented molecular mechanism of action.

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Cdc7 expression in melanomas, Spitz tumors and melanocytic nevi

Abstract: Cdc7 expression differs significantly among cutaneous melanocytic neoplasms and can be evaluated by routine immunohistochemical methods. The results suggest that differences in Cdc7 expression may account for some of the differences between malignant melanomas and benign melanocytic nevi.

Cited by 28 publications

References 15 publications

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

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

Overexpression of cell division cycle 7 homolog is associated with gene amplification frequency in breast cancer

Targeting Cell Division Cycle 7 Kinase: A New Approach for Cancer Therapy

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