PROX1-associated lymphatic reprogramming signatures in pediatric adamantinomatous craniopharyngioma: a comparative study with adult cases.
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BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is the most common sellar tumor in children. Although histologically benign, pediatric ACP often exhibits marked local invasiveness and a high postoperative recurrence rate. Emerging evidence suggests that the tumor microenvironment (TME), particularly immune infiltration and lymphatic-related structures, may play an important role in ACP progression. However, the presence and clinical relevance of lymphatic reprogramming in ACP remain poorly understood. METHODS: Publicly available single-cell RNA sequencing data from a pediatric ACP specimen were analyzed to characterize cellular composition and PROX1 expression patterns. Immunohistochemistry was subsequently performed on pediatric and adult ACP tissues to examine the spatial distribution and age-related expression of lymphatic markers, including PROX1 and LYVE1, as well as the vascular endothelial marker CD34. Quantitative comparisons between pediatric and adult cohorts were conducted. RESULTS: Single-cell analysis identified ten major cell populations within pediatric ACP, with epithelial cells accounting for approximately 40% of total PROX1 expression. Immunohistochemical validation revealed strong PROX1 expression predominantly localized to palisade-like and keratinized epithelial regions, while glial scar areas were largely negative. LYVE1-positive lymphatic-like structures were observed within the tumor parenchyma and showed partial spatial overlap with CD34-positive vascular structures, supporting the presence of PROX1-mediated lymphatic reprogramming. Notably, PROX1 and LYVE1 expression levels were significantly higher in pediatric ACP than in adult cases, indicating a marked age-dependent difference. CONCLUSIONS: Our findings demonstrate the presence of lymphatic-like structures characterized by PROX1 and LYVE1 expression in pediatric ACP, indicating that lymphatic-like reprogramming is associated with the tumor microenvironment. These features could potentially relate to the aggressive and infiltrative clinical behavior observed in pediatric cases. Therefore, exploring the modulation of PROX1-driven pathways warrants further investigation as a potential approach for pediatric ACP.