PRAME expression in cutaneous melanoma does not correlate with disease-specific survival.

BACKGROUND: Immunohistochemistry-based protein biomarkers can provide useful prognostic information in cutaneous melanoma. The independent prognostic value of Ki-67 has been studied with variable results. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a useful new ancillary tool for distinguishing cutaneous nevi from melanoma; however, its prognostic value has not been well studied. We evaluated PRAME as a prognostic marker in cutaneous melanoma, compared to Ki-67. METHODS: We analyzed the immunohistochemical expression of PRAME and Ki-67 in 165 melanocytic lesions, including 92 primary melanomas, 19 metastatic melanomas, and 54 melanocytic nevi using tissue microarrays. PRAME immunostaining was scored based on the percentage of positive nuclei: 0 <1%, 1+ 1%-25%, 2+ 26%-50%, 3+ 51%-75%, and 4+ >75%. The percentage of Ki-67-positive tumor nuclei was used to calculate the proliferation index. RESULTS: PRAME and Ki-67 both showed significantly increased expression in melanomas compared to nevi (p < 0.0001 and p < 0.001, respectively). There was no significant difference in PRAME expression in primary versus metastatic melanomas. By contrast, the Ki-67 proliferation index was higher in metastatic melanoma than in primary melanoma (p = 0.013). Increased Ki-67 index correlated with ulceration (p < 0.001), increased Breslow depth (p = 0.001), and higher mitotic rate (p < 0.0001), whereas increased PRAME expression correlated with higher mitotic rate (p = 0.047) and Ki-67 index (p = 0.007). Increased Ki-67 index correlated with worse disease-specific survival in patients with primary melanoma (p < 0.001), but PRAME expression did not show prognostic significance in disease-specific survival (p = 0.63). In a multivariable analysis of patients with primary melanoma, tumor Breslow depth, ulceration, mitotic rate, and Ki-67 index were each independent predictors of disease-specific survival (p = 0.006, 0.02, 0.001, and 0.04, respectively); however, PRAME expression was not predictive of disease-specific survival (p = 0.64). CONCLUSION: Ki-67 is an independent prognostic marker; although increased PRAME expression correlates with the Ki-67 proliferation index and mitotic rate, PRAME is not an independent prognostic marker for cutaneous melanoma. PRAME and Ki-67 are useful ancillary tools for distinguishing benign from malignant melanocytic lesions.

Diagnostic and Prognostic Value of ProEx C and GLUT1 in Melanocytic Lesions.

BACKGROUND: Melanoma is one of the most aggressive types of skin cancer. The purpose of this study was to evaluate the use of two biomarkers, ProEx C and glucose transporter isoform 1 (GLUT1), in the diagnosis and prognostication of melanoma. MATERIALS AND METHODS: We analyzed 129 melanomas and 59 benign nevi in a tissue microarray using immunohistochemical method with antibodies to topoisomerase IIα (TOP2A) and minichromosome maintenance complex component 2 (MCM2) using ProEx C and to GLUT1. RESULTS: The average proliferative index by ProEx C immunostain was significantly higher in melanomas (37.5%) compared to benign nevi (1.9%) as was the expression of GLUT1 (p<0.0001 respectively). Dermal mitosis was found to correlate positively with both ProEx C and GLUT1 (p=0.003 and p<0.001, respectively). Ulceration and tumor thickness positively correlated with GLUT1 expression (p=0.013 and p=0.033, respectively), but not with ProEx C staining. There was a significant association between increasing ProEx C index and stronger expression of GLUT1 (p<0.001). Kaplan-Meier disease-specific survival analyses indicated that patients whose melanoma exhibited expression of GLUT1 had a significantly lower rate of disease-specific survival than patients whose melanoma did not (p=0.039). However, staining by ProEx C did not show a prognostic significance in disease-specific survival. CONCLUSION: ProEx C and GLUT1 are potentially useful markers in differentiation of melanoma from nevi. Absence of GLUT1 expression in patients with primary melanoma predicts better survival.

Elafin is a biomarker of graft-versus-host disease of the skin.

Graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation, affects the skin, liver, and gastrointestinal tract. There are no plasma biomarkers specific for any acute GVHD target organ. We used a large-scale quantitative proteomic discovery procedure to identify biomarker candidates of skin GVHD and validated the lead candidate, elafin, with enzyme-linked immunosorbent assay in samples from 492 patients. Elafin was overexpressed in GVHD skin biopsies. Plasma concentrations of elafin were significantly higher at the onset of skin GVHD, correlated with the eventual maximum grade of GVHD, and were associated with a greater risk of death relative to other known risk factors (hazard ratio, 1.78). We conclude that elafin has significant diagnostic and prognostic value as a biomarker of skin GVHD.

Calretinin expression in tumors of adipose tissue.

Although well established as a marker of mesothelial cells, calretinin is also expressed in several other tissue types, including adipose tissue. Accordingly, immunohistochemical staining for calretinin has been described in an increasing number of neoplasms other than mesothelioma. A detailed analysis of calretinin expression in lipogenic tumors has not yet been reported, however. Given the known expression patterns of calretinin in normal tissues, we predicted that calretinin immunoreactivity would be detected in lipoma and the various histologic subtypes of liposarcoma, and that this marker might be of use in the differential diagnosis of selected fatty tumors. A variety of pleomorphic and small round cell sarcomas were studied for comparison. Calretinin immunoreactivity was detected, at least focally, in all 10 samples of normal adipose tissue and in 22 of 23 lipomas or lipoma variants. Staining for calretinin was also positive within the lipogenic component of 28 of 29 liposarcoma variants. Of the 7 dedifferentiated liposarcomas, 3 were focally positive for calretinin. Pleomorphic variants of other sarcomas, including undifferentiated high-grade pleomorphic sarcoma, rhabdomyosarcoma, leiomyosarcoma, and malignant peripheral nerve sheath tumor also exhibited focal calretinin immunoreactivity in a minority of cases, as did some small round cell sarcomas. These results suggest that calretinin immunoreactivity in normal and neoplastic adipose tissue is more ubiquitous than previously reported and may be a useful, albeit nonspecific marker of lipogenic differentiation. However, its utility in the differential diagnosis of fatty tumors appears limited.

Lymphangioma of the posterior mediastinum in an adult: diagnosis via cytopathologist-assisted fine-needle aspiration biopsy with cell block.

Lymphangiomas are uncommon in the posterior mediastinum. We report a case of a lymphangioma in this location that was diagnosed by computed tomographic-guided fine-needle aspiration biopsy. The cell block of the lesion closely simulated a normal structure immediately adjacent to the target and could have been misdiagnosed as "normal tissue." On-site evaluation of the aspirate by a cytopathologist promoted pathologist-radiologist communication that helped prevent the potential error and facilitated making the correct diagnosis in the case.