Clinical Significance of P16 in Langerhans Cell Histiocytosis

Background. The p16 protein has been identified as a tumor suppressor that functions by inhibiting the cyclin-dependent kinases CDK4 and CDK6. Deletions or point mutations in the p16 gene have been found in a number of human cancers, emphasizing its importance in regulating cell cycle progression. The authors have chosen to analyze P16 expression in biopsies from children with LCH and correlated it with clinical manifestation and outcome in a broad range of organs.

Patients and Methods: Archival paraffin block were retrieved from children diagnosed with LCH and followed up at Asan medical center and Chungnam National University Hospital between 1998 and 2007. Pathological Langerhans cells were identified morphologically associated with the characteristic inflammatory type infiltrate and were confirmed by immunohistochemical staining with antibodies to CD1a, and S100. The disease was classified as single system defined as uni- or multifocal involvement of a single organ system or multi-system defined as involvement of multiple organ systems with or without organ dysfunction. The slides were stained with P16 antibody and semi-quantitatively evaluated using 5 grade systems, negative means absence of staining, ±, weakly positive, +, similar with lymphocytes around the LCs, 2+, stronger than lymphocystes, 3+, much stronger than lymphocytes.

Results: The specimens from 57 patients (31 boys and 26 girls) were available for immunohistochemistry. Of these, 12 slides were not suitable because the quality of staining was not good for evaluation or the tumor cells are too difficult to be differentiated. The median age of 45 patients (24 boys and 21 girls) was 9.5 years, range 5 months to 22 years with a definite diagnosis of LCH based on CD1a positivity. The P16 protein was expressed in various degrees except one specimen. No significant difference was found between the level of P16 expression in lesions from patients with single-system, and multi-system disease. But higher tendency of relapse have shown in 1+, 2+ and 3+ groups compared with negative and weakly positive groups.

Conclusions: This study has shown a diffuse expression of P16 protein in both single and multi-system lesions of LCH. P16 might be involved in the pathogenesis of LCH.