Association of cell cycle-related gene products and NF-kappaB with clinical parameters in Langerhans cell histiocytosis.
BACKGROUND
Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the accumulation of abnormal Langerhans cells in one or several organs where they cause local tissue damage. The pathophysiology is not well understood. The aim of this study was to examine expression of various gene products that play a role in cell cycle and cell death and to look for an association with the extent of the disease at the time of diagnosis and with "risk bone" involvement.


METHODS
Histologic slides from cases with biopsy proven disease were stained immunohistochemically for Bcl-2, caspase-3, Ki-67, p53, and nuclear factor-kappaB (NF-kappaB) and the results were quantitated and compared with the clinical extent of the disease.


RESULTS
In patients with multisystem disease and "risk" bone involvement, a higher percentage of Langerhans cells stained with the anti-apoptotic gene product Bcl-2 (P = 0.0004; P = 0.001 respectively) and a lower percentage of these cells stained with the apoptosis marker caspase-3 compared to patients with single system disease (P = 0.0001; P = 0.01 respectively). Proliferation marker Ki-67 was expressed more frequently in multisystem disease compared to single system disease (P = 0.02) but an association with "risk" bone involvement was not found. Expression of p53 and NF-kappaB did not discriminate between clinical subgroups.


CONCLUSIONS
The findings suggest that cell proliferation and suppression of apoptosis may be mechanisms of cell survival in the more aggressive forms of LCH (multisystem, risk bone involvement).
Amir
Gail
G
Department of Pathology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel. gails@cc.huji.ac.il
Weintraub
Michael
M
D000293:Adolescent; D000328:Adult; D001847:Bone Diseases / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018816:Genes, cdc; D006646:Histiocytosis, Langerhans-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3