Faculty Bibliography

Decreased hydroxymethylated cytosine (5-hydroxymethycytosine, 5-hmC) is reported to correlate with melanocyte dysplasia. The purpose of this study was to assess the diagnostic utility of this observation. 5-hmC immunohistochemistry was performed on tissue microarrays containing 171-melanocytic lesions from two different institutions. An immunohistochemical staining score representing the percentage and intensity of nuclear staining was assigned. The performance characteristics of 5-hmC immunohistochemistry for discriminating between a nevus and melanoma were determined. Additional cases of melanoma arising in a nevus (n = 8), nodal nevi (n = 5) and melanoma micrometastases to a lymph node (n = 6) were also assessed. Pronounced 5-hmC loss was observed in melanomas when compared with nevi (mean +/- standard deviation = 6.71 +/- 11.78 and 55.19 +/- 23.66, respectively, p < 0.0001). While the mean immunohistochemical staining score values for melanocytic nevi and melanoma were distinct, there was considerable variability in immunohistochemical staining score within a single diagnostic category. The sensitivity and specificity of this assay for nevus vs. melanoma is 92.74 and 97.78%, respectively. Distinct biphasic staining patterns were observed in cases of melanoma arising in association with a nevus. Relative changes of 5-hmC expression within a single lesion may be more informative than absolute values when using 5-hmC as a diagnostic adjunct.

BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment option for mycosis fungoides (MF) and associated with few systemic side effects. OBJECTIVE: We sought to investigate whether there were differences in rates of ECP use between African-American and Caucasian patients with stage III/IV MF. METHODS: We conducted a retrospective review of all patients treated for MF at the Johns Hopkins Hospital main campus outpatient clinic between 1999 and 2011. RESULTS: We identified 65 patients with stage III or IV disease, 20 African-American and 45 Caucasian. Only 7 of 20 African-American patients (35%) compared with 30 of 45 (66%) of Caucasian patients were treated with ECP (p = 0.029). In addition, ECP was discussed as an option for 45% of African-Americans compared to 82% of Caucasians (p = 0.007). When discussed as an option, African-Americans and Caucasians had identical rates of ECP use (78% vs 81%, p = 0.841). CONCLUSIONS: Differences in rates of ECP use exist among African-American patients when compared to their Caucasian counterparts and may be related to how often ECP is offered as a treatment option. Improving physician awareness of the factors that influence treatment decision making may help diminish discrepancies in treatment regimens among patients with MF.

Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen.