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Xu, Shuyun

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Xu

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Shuyun

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Xu, Shuyun
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    5-Hydroxymethylcytosine Expression in Metastatic Melanoma versus Nodal Nevus in Sentine Lymph Node Biopsies
    (2014) Lee, Jonathan J.; Granter, Scott; Laga, Alvaro; Saavedra, Arturo; Zhan, Qian; Guo, Weimin; Xu, Shuyun; Murphy, George; Lian, Christine
    Sentinel lymph node biopsies are conducted to stage patients with newly-diagnosed melanomas that have histopathologic attributes conferring defined levels of metastatic potential. Because benign nevic cells may also form ‘deposits’ in lymph nodes (nodal nevus), the pathologic evaluation for metastatic melanoma within sentinel lymph nodes can be challenging. 28 sentinel lymph node biopsy cases containing either metastatic melanoma (N=18) or nodal nevi (N=10) were retrieved from the archives of the Brigham and Women’s Hospital Department of Pathology (2011–2014). In addition, two sentinel lymph node cases that were favored to represent metastatic disease but whose histopathologic features were viewed as equivocal, with melanoma favored, were also included. Dual-labeling for the melanocyte lineage marker, MART-1, and the epigenetic marker 5-hydroxymethylcytosine, a functionally-significant indicator that has been shown to distinguish benign nevi from melanoma, was performed on all cases using immunohistochemistry and/or direct immunofluorescence. All (18 of 18) metastatic melanoma cases showed complete loss of 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells and all (10 of 10) nodal nevus cases demonstrated 5-hydroxymethylcytosine nuclear staining in MART-1 positive cells. In addition, 5-hydroxymethylcytosine staining confirmed the favored diagnoses of metastatic melanoma in the two ‘equivocal’ cases. Thus, 5-hydroxymethylcytosine may be a useful adjunctive marker to distinguish between benign nodal nevi and metastatic melanoma during the evaluation of sentinel lymph node biopsies for metastatic melanoma.
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    Loss of the epigenetic mark, 5-Hydroxymethylcytosine, correlates with small cell/nevoid subpopulations and assists in microstaging of human melanoma
    (Impact Journals LLC, 2015) Lee, Jonathan J.; Cook, Martin; Mihm, Martin; Xu, Shuyun; Zhan, Qian; Wang, Thomas; Murphy, George; Lian, Christine
    Melanomas in the vertical growth phase (VGP) not infrequently demonstrate cellular heterogeneity. One commonly encountered subpopulation displays small cell/nevoid morphology. Although its significance remains unknown, such subpopulations may pose diagnostic issues when faced with differentiating such changes from associated nevus or mistaking such regions for nevic maturation (pseudomaturation). That ‘loss’ of the epigenetic biomarker, 5-hydroxymethylcytosine (5-hmC), is a hallmark for melanoma and correlates with virulence prompted us to explore the diagnostic utility and biological implications of 5-hmC immunohistochemistry (IHC) in melanomas with small cell/nevoid subpopulations. Fifty-two cases were included in this study, including melanomas with small cell/nevoid subpopulations (MSCN) or melanomas with pre-existing nevus (MPEN). Semiquantitative and computer-validated immunohistochemical analyses revealed invariable, uniform loss of 5-hmC in the conventional melanoma component. By contrast, the nevic components in MPEN cases demonstrated strong nuclear immunopositivity. In MSCN cases, there was partial to complete loss of 5-hmC restricted to these nevoid areas. Based on recent data supporting tight correlation between 5-hmC loss and malignancy, our findings indicate a potential ‘intermediate’ biological nature for small cell/nevoid subpopulations. Because 5-hmC assisted in differentiating such regions from associated nevus, the use of 5-hmC as an adjunct to microstaging in difficult cases showing VGP heterogeneity should be further explored.
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    Novel Genetic Mutations in a Sporadic Port-Wine Stain
    (American Medical Association (AMA), 2014) Lian, Christine; Sholl, Lynette; Zakka, Labib; O, Teresa M.; Liu, Cynthia; Xu, Shuyun; Stanek, Ewelina; Garcia, Elizabeth; Jia, Yonghui; MacConaill, Laura; Murphy, George; Waner, Milton; Mihm, Martin
    Importance Port-wine stains (PWSs) are common congenital cutaneous capillary malformations. A somatic GNAQ mutation was recently identified in patients with sporadic PWSs and Sturge-Weber syndrome. However, subsequent studies to confirm or extend this observation are lacking. Observations We report a long-standing, unilateral facial PWS of a man in his early 70s confirmed by histopathological analysis. Staged surgical excision of the vascular malformation was performed, and genomic DNA was extracted from the vascular malformation specimen and normal skin. Targeted next-generation sequencing of the coding sequence of 275 known cancer genes including GNAQ was performed in both specimens. A single-nucleotide variant (c.548G>A, p.Arg183Gln) in GNAQ was identified in the PWS-affected tissue but not in the normal skin sample. In addition, this sequencing approach uncovered several additional novel somatic mutations in the genes SMARCA4, EPHA3, MYB, PDGFR-β, and PIK3CA. Conclusions and Relevance Our findings confirm the presence of somatic mutations in GNAQ in the affected skin of a patient with congenital PWS, as well as alterations in several other novel genes of possible importance in the pathogenesis of PWS that may also offer substantial therapeutic targets.