PRAME (Preferentially Expressed Antigen In Melanoma)

SOX10 and PRAME are nuclear staining markers that can be used for diagnostic purposes and as adjunct markers for the diagnosis of VM and benign melanocytic lesions. PRAME immunostaining shows high specificity for melanoma and melanoma in situ.

In contrast, the p.H169Y and p.G185R variants appear to uniquely preserve both protein folding and nuclear localization, allowing retained nuclear expression despite functional inactivation. Therefore, in tumors with morphologic features suggestive of BIMT, retained BAP1 nuclear expression should not preclude diagnosis or additional molecular testing to confirm BAP1 inactivation.

Melanoma should be taken into consideration in the differential diagnosis of adult intussusception and small bowel tumors, even without a known primary lesion. This particular case highlights the importance of HP evaluation and multidisciplinary assessment in reaching an accurate diagnosis.

In 2022, tebentafusp became the first approved systemic therapy to improve overall survival in metastatic UM...As half of the patients are HLA A02:01 negative, alternative strategies are under investigation, including the protein kinase C inhibitor darovasertib in the NADOM neoadjuvant/adjuvant trial and in combination with crizotinib in metastatic UM. DYP688, a first-in-class PMEL17-targeting antibody-drug conjugate that inhibits GNAQ/11 signaling, has shown promise in metastatic UM and other GNAQ/11-mutant melanomas. The landscape of UM treatment is rapidly evolving following the identification of new targets and pathways such as PKC or PRAME. Combination of liver-directed therapies with personalized systemic immunotherapies or targeted agents in the metastatic disease, as well as the early use of systemic therapies in the primary tumor setting will refine treatment strategies in UM and suggest improved outcomes in the near future.

P1/2, N=410, Active, not recruiting, Immunocore Ltd | Recruiting --> Active, not recruiting | N=727 --> 410 | Trial completion date: Aug 2026 --> Dec 2027 | Trial primary completion date: Feb 2026 --> Oct 2026

Cases of malignant peripheral nerve sheath tumours are, in contrast to desmoplastic melanoma S‑100 protein negative or express this marker only focally, and show a decreased nuclear expression of H3K27. Desmoplastic melanoma shows a focal nuclear expression of p53 in contrast to neurofibroma.

Both fusions preserved the BRAF kinase domain while eliminating its N-terminal regulatory regions. These cases expand the molecular spectrum of Spitz neoplasms and underscore neurotropism as a potential morphologic clue for BRAF fusion-driven Spitz nevi.

HN-NCs had dismal prognosis, especially those originating from oral mucosa. HN-NC should be included in the differential diagnosis when encountering poorly differentiated/undifferentiated malignancies or carcinomas with squamous differentiation.

Radiation therapy and imatinib may be considered for unresectable tumors, and we advise that COL1A1-PDGFB fusion is confirmed before starting imatinib...Advances in organoid models and single-cell RNA sequencing have improved understanding of the tumor microenvironment. However, racial disparities in diagnosis and treatment emphasize the need for a high index of suspicion in skin of color patients to reduce misdiagnosis and delays in care.

Together, these findings suggest that PRAME and ETS2 cooperatively suppress ciliogenesis in melanoma cells, proposing a previously unrecognized epigenetic mechanism of ciliary loss. This mechanism broadens our understanding of melanoma progression and highlights the role of the PRAME-ETS2-HDAC1 axis in regulating ciliogenesis.

We constructed a novel prognostic model based on 15 PFAS-related DEGs to predict the survival and responses to potential drugs and immunotherapy of CRC patients. Furthermore, we identified and assessed the feasibility of the critical gene PRAME in prognostic model as a vital marker for CRC. Our findings further suggested that PFOS exposure may increase the risk of CRC development via upregulation of PRAME-mediated PI3K/Akt/mTOR signalling pathway, indicating its potential as a novel therapeutic target for CRC in the future.