Defining a Unique Gene Expression Profile in Mature and Developing Keloids.

Keloids are benign, fibroproliferative dermal tumors that typically form owing to abnormal wound healing. The current standard of care is generally ineffective and does not prevent recurrence. To characterize keloid scars and better understand the mechanism of their formation, we performed transcriptomic profiling of keloid biopsies from a total of 25 subjects of diverse racial and ethnic origins, 15 of whom provided a paired nonlesional sample, a longitudinal sample, or both. The transcriptomic signature of nonlesional skin biopsies from subjects with keloids resembled that of control skin at baseline but shifted to closely match that of keloid skin after dermal trauma. Peripheral keloid skin and rebiopsied surrounding normal skin both showed upregulation of epithelial-mesenchymal transition markers, extracellular matrix organization, and collagen genes. These keloid signatures strongly overlapped those from healthy wound healing studies, usually with greater perturbations, reinforcing our understanding of keloids as dysregulated and exuberant wound healing. In addition, 219 genes uniquely regulated in keloids but not in normal injured or uninjured skin were also identified. This study provides insights into mature and developing keloid signatures that can act as a basis for further validation and target identification in the search for transformative keloid treatments.

Risks for noncutaneous second primary malignancy in cutaneous malignant melanoma survivors: an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) program.

BACKGROUND: It is known that malignant melanoma (MM) survivors are at increased risk of future primary MM. However, the risk for noncutaneous second primary malignancies (SPMs) is not as well-understood. METHODS: An observational study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database was performed, assessing data from patients diagnosed with primary cutaneous MM to measure overall, as well as specific, tumor type and risk of SPM. RESULTS: Of the 132,438 patients recruited in the study population (mean age 55.5 years; 54% male), 23,794 SPMs were observed (O) (18% of patients at a mean age of 68.8 years), while 17,923 SPMs were expected (E) to occur (O : E 1.33, 95% CI 1.31-1.34). Excluding cutaneous MM occurring as a new primary malignancy, there was a significantly increased risk for SPMs among cutaneous MM survivors for each of the following tumor types: eye and orbit melanoma, tracheal, thyroid, salivary gland, retroperitoneum, small intestine, kidney, lymphoid and hematopoietic system, lymphoma overall, non-Hodgkin lymphoma, lymphocytic leukemia overall, chronic lymphocytic leukemia, male genital system (including prostate), and breast. Certain gender-specific trends for SPMs were also detected. CONCLUSIONS: Patients with primary cutaneous MM are at increased risk for primary noncutaneous MM as well as noncutaneous SPMs that include numerous tumor types. Enhanced oncologic surveillance for a variety of tumor types in melanoma survivors is warranted.