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Biomedical subjects

Lyn M Duncan

Publications and source records attributed to Lyn M Duncan.

12 recordsLinked to original sources
PubMed2006

Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene.

Genomes of human cancer cells are characterized by numerous chromosomal aberrations of uncertain pathogenetic significance. Here, in an inducible mouse model of melanoma, we characterized metastatic variants with an acquired focal chromosomal amplification that corresponds to a much larger amplification in human metastatic melanomas. Further analyses identified Nedd9, an adaptor protein related to p130CAS, as the only gene within the minimal common region that exhibited amplification-associated overexpression. A series of functional, biochemical, and clinical studies established NEDD9 as a bona fide melanoma metastasis gene. NEDD9 enhanced invasion in vitro and metastasis in vivo of both normal and transformed melanocytes, functionally interacted with focal adhesion kinase and modulated focal contact formation, and exhibited frequent robust overexpression in human metastatic melanoma relative to primary melanoma. Thus, comparative oncogenomics has enabled the identification and facilitated the validation of a highly relevant cancer gene governing metastatic potential in human melanoma.

Adaptor Proteins, Signal Transducing↗
PubMed2005

WHO-EORTC classification for cutaneous lymphomas.

Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification.

Humans↗
PubMed2005

Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management.

Congenital melanocytic nevi occur in approximately 1% of newborns and are usually classified according to their size. Giant congenital melanocytic nevi are most simply defined as melanocytic nevi that are greater than 20 cm in largest dimension; whereas small congenital nevi are defined as melanocytic nevi less that 1.5 cm in largest dimension. Congenital nevi can exhibit distinctive histologic features that can help in differentiating them from common acquired nevi. Giant congenital melanocytic nevi are associated with an increased risk of the development of melanoma. On the other hand, there is evidence of an increased melanoma risk in patients with small congenital nevi. Nevertheless, the risk of malignant transformation in small congenital nevi and the lifetime melanoma risk in patients with small congenital nevi remain controversial. In large part due to inconsistency in the reported literature describing patients with congenital melanocytic nevi, the risk of melanoma in these patients remains unclear and consistent guidelines for clinical management do not exist. We review the literature and comment on the course of management for these patients at the Massachusetts General Hospital Pigmented Lesion Clinic.

Abnormalities, Multiple↗
PubMed2005

Cutaneous metastases of follicular thyroid carcinoma: a report of four cases and a review of the literature.

Cutaneous metastasis of follicular carcinoma of the thyroid is very rare, and when it occurs, can exhibit a variety of histologic appearances. The 4 cases presented here were identified from the surgical pathology files of the James Homer Wright Laboratories of Pathology at the Massachusetts General Hospital (MGH). The cases consisted of 4 patients, 3 men and 1 woman, aged 52 to 75 years, with cutaneous metastasis of follicular thyroid carcinoma. The tumors include a conventional follicular carcinoma, a follicular carcinoma with anaplastic transformation following initial metastasis, the first reported cutaneous metastases of a follicular carcinoma with oncocytic features (Hürthle cell carcinoma), and a follicular carcinoma with a prominent insular carcinoma component. All 4 tumors were widely invasive within the thyroid gland. Sites of dermal metastases included a post-thyroidectomy scar, scalp, and sacral skin. Three metastases retained the morphologic and immunocytochemical features of the primary thyroid tumors. However, in one case there was high-grade transformation to anaplastic carcinoma following treatment of a sacral metastasis with accompanying loss of the characteristic immunophenotype of follicular thyroid carcinoma. Awareness of the varied morphologies of metastatic follicular thyroid carcinoma to the skin may prompt immunohistochemical analysis and the request for a complete clinical history, ultimately preventing misdiagnosis.

Adenocarcinoma, Follicular↗
PubMed2004

HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma.

The diagnosis of melanoma metastatic to lymph node remains a difficult problem given its histological diversity. We examined the staining patterns of S-100, NK1/C3, HMB-45, and MART-1 (DC10) in melanoma metastases to lymph nodes. Immunohistochemical stains were performed on tissue sections of 126 formalin-fixed lymph nodes from 126 patients with an established diagnosis of metastatic melanoma. A total of 98% of cases (123 of 126) stained positive for S-100, 93% (117 of 125) stained positive for NK1/C3, 82% (103 of 126) stained positive for MART-1, and 76% (95 of 125) stained positive for HMB-45. The distribution and intensity of staining varied among these markers. A diffuse staining pattern, defined as >50% of tumor cells stained, was observed in 83% of MART-1-positive cases but in only 56% of S-100-positive cases, 48% of NK1/C3-positive cases, and 34% of HMB-45-positive cases. A maximally intense signal was almost always observed for MART-1 (83% of positive cases) but was rarely observed for NK1/C3 (20%). S-100 and HMB-45 showed maximally intense staining in 50% and 54% of cases, respectively. S-100 and NK1/C3 stained both histiocytes and melanocytes, whereas MART-1 and HMB-45 stained only melanocytes. Seventy-eight cases (63%) stained positive for all 4 markers, 17 cases (14%) stained for all markers except HMB-45, 13 cases (10%) stained for all markers except MART-1, 6 cases (5%) stained only with S-100 and NK1/C3, 4 cases (3%) stained only with S-100 and HMB-45, and 2 cases stained for all markers except S-100. One case each stained for the following: only S-100, only S-100 and HMB-45, and all markers except NK1/C3. One case exhibited absence of staining for any of these markers. We demonstrate that lymph node metastases of melanoma are heterogeneous with regard to tumor marker expression. S-100 and NK1/C3 were the most sensitive stains for detecting metastatic melanoma; however, they both also stain other nontumor cells in lymph nodes. MART-1 did not stain histiocytes and exhibited a more frequently intense and diffuse staining pattern than NK1/C3. HMB-45 was less sensitive and demonstrated less diffuse staining than MART-1.

Antigens↗
PubMed2003

Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop.

BACKGROUND: Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS: This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. RESULTS: Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. CONCLUSIONS: Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded.

CD4-Positive T-Lymphocytes↗