Genotypic analysis of pulmonary Langerhans cell histiocytosis.
Reported studies show that the systemic form of Langerhans cell histiocytosis (LCH) is a clonal expansion of Langerhans cells (LC) associated with aberrant expression of several oncogenes or tumor-suppressor genes. LCH of the lung is a heterogenous group of lesions thought to be a reactive rather than neoplastic process. The histogenesis of the LCH of the lung is uncertain, and to date there are no studies investigating its underlying molecular abnormalities. We performed comparative genotypic analysis by using allelic loss (LOH) of polymorphic microsatellite markers associated with tumor suppressor genes. Fourteen cases of formalin-fixed, paraffin-embedded LCH of the lung were studied. Microdissection of a total of 26 nodules from 14 patients and paired reference lung tissue was performed under stereomicroscopic visualization. To evaluate allelic loss, we used a panel of 11 polymorphic microsatellite markers that were situated at or near tumor suppressor genes on chromosomes 1p, 1q, 3p, 5p, 9p, 17p, and 22q. The PCR products were analyzed by using capillary electrophoresis to identify germline heterozygous alleles and LOH. Allelic loss at 1 or more tumor suppressor gene loci was identified in 19 of 24 nodules. The total fractional allelic loss (FAL) ranged from 6% (1q) to 41% (22q), with a mean of 22%. The FAL in individual cases ranged from 0 (7 nodules) to 57% (1 nodule). Fifteen discordant allelic losses at 1 to 3 chromosomal loci were identified in 8 patients with multiple synchronous nodules. Our results show that LOH of tumor suppressor genes is present in the LCH of the lung, and they indicate that the putative tumor suppressor genes situated on chromosomes 9p and 22q may play a role in the development of a subset of the LCH of the lung.
Dacic
S
S
Department of Pathology, Division of Anatomic Pathology, University of Pittsburgh Medical Center, PA 15213, USA.
Trusky
C
C
Bakker
A
A
Finkelstein
S D
SD
Yousem
S A
SA
D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000032:analysis; D019075:Electrophoresis, Capillary; D005260:Female; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006646:Histiocytosis, Langerhans-Cell / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D042282:Microdissection; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm