Korean J Hematol.  2012 Dec;47(4):267-272. 10.5045/kjh.2012.47.4.267.

Prognostic significance of gelsolin and MMP12 in Langerhans cell histiocytosis

• Seo JJ
• Cho T
• Kim SY
• Nassour I
• Kim HJ
• Lim YJ
• Koh KN
• Im HJ

• KMID: 1832105
• DOI: http://doi.org/10.5045/kjh.2012.47.4.267

Abstract

BACKGROUND
Gelsolin and matrix metalloproteinase 12 (MMP12) expression has been reported in Langerhans cell histiocytosis (LCH), but the clinical significance of this expression is unknown. We investigated the associations of these proteins with clinical manifestations in patients diagnosed with LCH.
METHODS
We performed a retrospective analysis of clinical data from patients diagnosed with LCH and followed up between 1998 and 2008. Available formalin-fixed, paraffin-embedded specimens were used for gelsolin and MMP12 immunohistochemical staining. We analyzed the expression levels of these proteins and their associations with LCH clinical features.
RESULTS
Specimens from 36 patients (20 males, 16 females) with a diagnosis of LCH based on CD1a positivity with clinical manifestations were available for immunohistochemical staining. Median patient age was 62 months (range, 5 to 207). The expression of gelsolin varied; it was high in 17 patients (47.2%), low in 11 patients (30.6%), and absent in 8 patients (22.2%). The high gelsolin expression group had a higher tendency for multi-organ and risk organ involvement, although the trend was not statistically significant. MMP12 was detected only in 7 patients (19.4%) who showed multi-system involvement (P=0.018) and lower event-free survival (P=0.002) in comparison to patients with negative MMP12 staining.
CONCLUSION
Gelsolin and MMP12 expression may be associated with the clinical course of LCH, and MMP12 expression may be particularly associated with severe LCH. Further studies of larger populations are needed to define the precise role and significance of gelsolin and MMP12 in the pathogenesis of LCH.

Keyword

Histiocytosis; Langerhans cells; Immunohistochemistry; Gelsolin; Matrix Metalloproteinase 12

MeSH Terms

Disease-Free Survival
Gelsolin
Histiocytosis
Histiocytosis, Langerhans-Cell
Humans
Immunohistochemistry
Langerhans Cells
Male
Matrix Metalloproteinase 12
Proteins
Retrospective Studies
Gelsolin
Matrix Metalloproteinase 12
Proteins

Figure

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  Fig. 1 Light micrographs of LCH lesions after gelsolin immunohistochemical staining (×400). Scattered LCs with reddish brown reactions in the cytoplasm were considered positive. A semi-quantitative evaluation was made using the following grading system: negative (A), lower expression group (LEG) (B) and higher expression group (HEG) (C) according to the extent of cytoplasmic staining.

• 

  Fig. 2 Light micrographs of LCH lesions after MMP12 immunohistochemical staining (400×). Slides with no staining were regarded as negative (A), whereas LCs with light brown reactions in the cytoplasm were considered positive (B).

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  Fig. 3 Event-free survival (EFS) rates according to immunohistochemical grade. (A) The probability of EFS according to the gelsolin expression. The EFS was 94.7% for LEG patients and 78.6% for HEG patients. The difference was not statistically significant according to the log-rank test (P=0.222). (B) The probability of EFS in terms of MMP positivity. EFS for the negative group was 96.6%, while that of the positive group was 57.1%, a statistically significant difference according to the log-rank test (P=0.002).

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