Immunohistochemical analyses of p16 and beta-catenin in solitary fibrous tumors might define different biological subgroups

Background Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms with an incidence of 0.98 cases per million persons annually. While STAT6, CD34, bcl-2, and CD99 positivity are hallmark immunohistochemical findings, the role of beta-catenin remains controversial. In addition to beta-catenin, a recent study described p16-expression as futher morphological feature [1]. However, a direct comparison of the latter two in SFTs has not yet been performed, leaving a gap in understanding their significance for diagnostics and disease progression.

Methods & Materials We examined resected specimens from 30 patients, including 14 with extrapleural and 16 with pleural SFTs, with surgeries conducted between 2013 and 2024. Tumors were evaluated for size, localization, patient demographics and metastasis status. Immunohistochemical markers included STAT6, CD34, bcl-2, CD99, p16, beta-catenin, p53, and Mib-1/Ki67. Based on immunohistochemical profiles, tumors were categorized into distinct subgroups and correlated with Demicco risk grading.

Results The cohort consisted of 17 female and 13 male patients, aged 20–85 years (median: 68). Tumor sizes ranged from 0.9 to 18.8 cm. We identified three immunohistochemical subgroups that correlated with the risk categories defined by Demicco grading: (1) Beta-catenin nuclear-positive/p16-negative (33,33%): These tumors were exclusively localized to the pleura and demonstrated low to intermediate risk for recurrence. (2) P16-positive/beta-catenin-negative (40%): This subgroup was associated with p53 overexpression, an elevated risk of metastasis and the poorest progression-free survival outcomes. (3) Negative for both markers (26,67%): These tumors were categorized as low risk. The p16-positive subgroup exhibited the highest rates of metastasis and tumor-associated mortality. In one case, marker profiles shifted during disease progression, as observed where a p16-positive primary SFT became beta-catenin-positive upon pleural metastasis.

Conclusion Our findings suggest three immunohistochemical subgroups of SFTs with distinct prognostic and biological behaviors. These groups align with Demicco grading and highlight the pleura as a unique site for nuclear beta-catenin-positivity. Further molecular investigations are needed to address the underlying mechanism of p16-positivity, as well as of the observed shift in marker expression during metastasis.

 

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• Literatur

• 1 Yamada Y et al. Histological background of dedifferentiated solitary fibrous tumour. J Clin Pathol. 2022; 397-403

Publication History

Article published online:
25 August 2025