5-Hydroxymethylcytosine as a useful marker to differentiate between malignant melanomas and benign melanocytic nevi

5-Hydroxymethylcytosine: An epigenetic mark frequently deregulated in cancer

“…Diminished expression of IDH2 and TET1/2/3 was reported in melanoma, and therefore may represent one of the molecular mechanisms underlying global 5hmC loss in these tumors [31]. 5hmC levels were decreased in melanoma but not in benign nevi, showing the potential of 5hmC levels to be used as a biomarker to discriminate between benign and malignant lesions [67]. 5mC levels did not differ significantly between melanoma and benign nevi [68].…”

The role of 5-hydroxymethylcytosine in human cancer

“…Some interesting data are already available suggesting that this type of approach may be feasible. For example, in several studies of human benign, pre-malignant and malignant melanocytic lesions, it was shown that benign nevi, dysplastic nevi and Spitz nevi show normal levels of 5hmC, but 5hmC is drastically reduced in malignant melanoma specimens (Lian, et al, 2012, Gambichler, et al, 2013, Larson, et al, 2014, Uchiyama, et al, 2014). A standard biomarker used in diagnostic pathology examinations to score for presence or absence of malignant cells in tissue biopsies is the proliferation marker Ki67, a nuclear antigen that is present in actively dividing cells.…”

Melanoma epigenetics: novel mechanisms, markers, and medicines

“…We have also found that a strong correlation exists between the loss of 5-hmC and with the parameters of poor prognosis in melanoma, including Breslow depth, mitotic rate, ulceration, as well as with lower overall survival, suggesting a potential predictive value of loss of 5-hmC (71). Others have since reproduced these findings (72, 73). …”

“…The retention of 5-hmC nuclear staining was very recently documented in certain benign nevic subtypes, including the Spitz nevus, whereas the loss of 5-hmC was found to be a feature in multiple melanoma subtypes, including both acral and mucosal melanoma (73). Moreover, the loss of 5-hmC may be a common feature of malignant melanoma, despite varying etiologies; melanomas arising in chronically sun-damaged skin as well as those arising in sun-protected areas, or non-chronically sun-damaged skin, too, demonstrate this epigenetic phenomenon (73). Thus, it appears that whether it reflects a primary pathobiologic event or is a byproduct of a malignant epigenetic state, the loss of 5-hmC may be a common epigenetic hallmark for cellular malignancy.…”

“…Moreover, identification of these epigenetic hallmarks circulating as free DNA in the serum of patients with melanoma using methylation-specific polymerase chain reaction is also an area of active investigation (147). In addition, the loss of 5-hmC, as demonstrated through immunohistochemistry, may aid in distinguishing malignant melanocytic lesions from dysplastic or borderline melanocytic lesions wherein 5-hmC staining is relatively more intense (71–73). The diagnostic utility and prognostic significance of loss of 5-hmC by immunohistochemistry, as has been demonstrated in melanoma (71), also has been recapitulated in other human tumors, including oral squamous cell carcinoma (28), gastrointestinal stromal tumor (29), and hepatocellular carcinoma (30).…”