Person: Duncan, Lyn
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Duncan
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Lyn
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Duncan, Lyn
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Publication Whole-Slide Imaging Digital Pathology as a Platform for Teleconsultation: A Pilot Study Using Paired Subspecialist Correlations(College of American Pathologists, 2009) Lauwers, Gregory Y.; Wilbur, David; Madi, Kalil; Colvin, Robert; Duncan, Lyn; Faquin, William; Ferry, Judith; Frosch, Matthew; Houser, Stuart L.; Kradin, Richard; Louis, David; Mark, Eugene; Mino-Kenudson, Mari; Misdraji, Joseph; Nielsen, Gunnlauger P.; Pitman, Martha; Rosenberg, Andrew Eric; Smith, R. Neal; Sohani, Aliyah; Stone, James; Tambouret, Rosemary; Wu, Chin-Lee; Young, Robert; Zembowicz, Artur; Wlietmann, WolfgangContext.—Whole-slide imaging technology offers promise for rapid, Internet-based telepathology consultations between institutions. Before implementation, technical issues, pathologist adaptability, and morphologic pitfalls must be well characterized. Objective.—To determine whether interpretation of whole-slide images differed from glass-slide interpretation in difficult surgical pathology cases. Design.—Diagnostically challenging pathology slides from a variety of anatomic sites from an outside laboratory were scanned into whole digital format. Digital and glass slides were independently diagnosed by 2 subspecialty pathologists. Reference, digital, and glass-slide interpretations were compared. Operator comments on technical issues were gathered. Results.—Fifty-three case pairs were analyzed. There was agreement among digital, glass, and reference diagnoses in 45 cases (85%) and between digital and glass diagnoses in 48 (91%) cases. There were 5 digital cases (9%) discordant with both reference and glass diagnoses. Further review of each of these cases indicated an incorrect digital whole-slide interpretation. Neoplastic cases showed better correlation (93%) than did cases of nonneoplastic disease (88%). Comments on discordant cases related to digital whole technology focused on issues such as fine resolution and navigating ability at high magnification. Conclusions.—Overall concordance between digital whole-slide and standard glass-slide interpretations was good at 91%. Adjustments in technology, case selection, and technology familiarization should improve performance, making digital whole-slide review feasible for broader telepathology subspecialty consultation applications.Publication Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+ T Cells in Cutaneous Melanoma(Hindawi Publishing Corporation, 2015) Giavina-Bianchi, Mara; Giavina-Bianchi, Pedro; Sotto, Mirian Nacagami; Muzikansky, Alona; Kalil, Jorge; Festa-Neto, Cyro; Duncan, LynNY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.Publication MGH Whole Slide Imaging Teleconsultation Practice in Dermatopathology(Hindawi Publishing Corporation, 2014) Jones, Nicholas C.; Nazarian, Rosalynn; Duncan, Lyn; Wilbur, DavidPublication Integrative Genome Comparison of Primary and Metastatic Melanomas(Public Library of Science, 2010) Kabbarah, Omar; Nogueira, Cristina; Feng, Bin; Bosenberg, Marcus; Scott, Kenneth L.; Xiao, Yonghong; Cordon-Cardo, Carlos; Wagner, Stephan N.; Brennan, Cameron; Nazarian, Rosalynn; Wu, Min; Kwong, Lawrence Noc-Woon; Granter, Scott; Ramaswamy, Sridhar; Golub, Todd; Duncan, Lyn; Chin, LyndaA cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes.Publication Resistance to checkpoint blockade therapy through inactivation of antigen presentation(Nature Publishing Group UK, 2017) Sade-Feldman, Moshe; Jiao, Yunxin J.; Chen, Jonathan; Rooney, Michael S.; Barzily-Rokni, Michal; Eliane, Jean-Pierre; Bjorgaard, Stacey L.; Hammond, Marc R.; Vitzthum, Hans; Blackmon, Shauna M.; Frederick, Dennie T.; Hazar-Rethinam, Mehlika; Nadres, Brandon A.; Van Seventer, Emily E.; Shukla, Sachet A.; Yizhak, Keren; Ray, John P.; Rosebrock, Daniel; Livitz, Dimitri; Adalsteinsson, Viktor; Getz, Gad; Duncan, Lyn; Li, Bo; Corcoran, Ryan; Lawrence, Donald; Stemmer-Rachamimov, Anat; Boland, Genevieve; Landau, Dan A.; Flaherty, Keith; Sullivan, Ryan; Hacohen, NirTreatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29.4% of patients with progressing disease. In two independent cohorts of melanoma patients treated with anti-CTLA4 and anti-PD1, respectively, we find that B2M LOH is enriched threefold in non-responders (~30%) compared to responders (~10%) and associated with poorer overall survival. Loss of both copies of B2M is found only in non-responders. B2M loss is likely a common mechanism of resistance to therapies targeting CTLA4 or PD1.