Korean J Hematol.  2010 Dec;45(4):247-252. 10.5045/kjh.2010.45.4.247.

Role of p16 in the pathogenesis of Langerhans cell histiocytosis

• Kim SY
• Kim HJ
• Kim HJ
• Park MR
• Koh KN
• Im HJ
• Lee CH
• Seo JJ

• KMID: 2252035
• DOI: http://doi.org/10.5045/kjh.2010.45.4.247

Abstract

BACKGROUND
It has been hypothesized that genetic alteration at the cellular level may have a significant effect on cellular mechanisms controlling the proliferation and apoptosis of Langerhans cells (LCs).
METHODS
We examined whether p16 protein expression can be used to predict the outcome of Langerhans cell histiocytosis (LCH). Archival paraffin blocks from children diagnosed with LCH and followed at the Asan Medical Center and Chungnam National University Hospital between March 1998 and February 2008 were studied.
RESULTS
Slides were stained with p16 antibody and evaluated semi-quantitatively using the following scale: negative, no staining; +/-, weakly positive; 1+, staining similar to lymphocytes surrounding the LCs; 2+, stronger staining than lymphocytes; 3+, much stronger staining than lymphocytes. Negative and +/- groups were assigned to a lower expression group (LEG) and the 1+, 2+, and 3+ groups were assigned to a higher expression group (HEG). The median age of the 51 patients (24 girls, 27 boys) was 49 (range, 0.6-178) months, and LCH was diagnosed based on CD1a positivity. p16 protein was expressed to varying degrees in all but one specimen. There was a greater tendency toward multisystem disease, risk organ involvement, and relapse in the HEG than in the LEG.
CONCLUSION
The p16 protein may have a significant effect on cellular mechanisms controlling the proliferation and apoptosis of LCs, and thus may influence the clinical outcome and prognosis of LCH.

Keyword

Genes; p16; Histiocytosis; Langerhans cells; Immunohistochemistry

MeSH Terms

Apoptosis
Child
Histiocytosis
Histiocytosis, Langerhans-Cell
Humans
Immunohistochemistry
Langerhans Cells
Lymphocytes
Paraffin
Prognosis
Recurrence
Paraffin

Figure

• 

  Fig. 1 Light micrographs of LCH lesions after immunohistochemical staining (×400). Scattered morphologically positive LCs are shown. A semi-quantitative evaluation was made using the following grading system: negative, no staining; ±, weakly positive (A) 1+, staining similar to lymphocytes surrounding the LCs (B) 2+, stronger staining than lymphocytes (C) 3+, much stronger staining than lymphocytes (D).

• 

  Fig. 2 Six-year event-free survival (EFS) rate according to immunohistochemical grade. The probability of 6-year EFS for LEG patients was 92.9±6.9%, whereas that for HEG patients was 70.3±8.1%. The difference was not significant according to the log-rank test.

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