Original Article

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Korean J Hematol 2010; 45(4):

Published online December 31, 2010

https://doi.org/10.5045/kjh.2010.45.4.247

© The Korean Society of Hematology

Role of p16 in the pathogenesis of Langerhans cell histiocytosis

Sun-Young Kim1, Hyoung-Jin Kim1, Hee-Jin Kim2, Mee-Rim Park3, Kyung-Nam Koh3, Ho-Joon Im3, Chul-Hoon Lee4, and Jong-Jin Seo3*

1Department of Pediatrics, College of Medicine, Hanyang University Hospital, Seoul, Korea.

2Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

3Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine & Asan Medical Center, Seoul, Korea.

4Department of Medical Genetics, College of Medicine, Hanyang University, Seoul, Korea.

Correspondence to : Correspondence to Jong Jin Seo, M.D. Division of Pediatrics Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine & Asan Medical Center, 388-1, Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3383, Fax: +82-2-473-3725, jjseo@amc.seoul.kr

Received: September 1, 2010; Revised: October 6, 2010; Accepted: November 18, 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords Genes, p16, Histiocytosis, Langerhans cells, Immunohistochemistry

Article

Original Article

Korean J Hematol 2010; 45(4): 247-252

Published online December 31, 2010 https://doi.org/10.5045/kjh.2010.45.4.247

Copyright © The Korean Society of Hematology.

Role of p16 in the pathogenesis of Langerhans cell histiocytosis

Sun-Young Kim1, Hyoung-Jin Kim1, Hee-Jin Kim2, Mee-Rim Park3, Kyung-Nam Koh3, Ho-Joon Im3, Chul-Hoon Lee4, and Jong-Jin Seo3*

1Department of Pediatrics, College of Medicine, Hanyang University Hospital, Seoul, Korea.

2Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

3Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine & Asan Medical Center, Seoul, Korea.

4Department of Medical Genetics, College of Medicine, Hanyang University, Seoul, Korea.

Correspondence to: Correspondence to Jong Jin Seo, M.D. Division of Pediatrics Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine & Asan Medical Center, 388-1, Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3383, Fax: +82-2-473-3725, jjseo@amc.seoul.kr

Received: September 1, 2010; Revised: October 6, 2010; Accepted: November 18, 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Genes, p16, Histiocytosis, Langerhans cells, Immunohistochemistry

Fig 1.

Figure 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).

Blood Research 2010; 45: 247-252https://doi.org/10.5045/kjh.2010.45.4.247

Fig 2.

Figure 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.

Blood Research 2010; 45: 247-252https://doi.org/10.5045/kjh.2010.45.4.247

Table 1 . Clinical manifestations according to the immunohistochemical grade..

Abbreviations: LEG, lower expression group; HEG, higher expression group..


Table 2 . Organ involvement according to the immunohistochemical grade..

Abbreviations: LEG, lower expression group; HEG, higher expression group..


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