Chromosomal aberrations, profiles of expression of growth-related markers including galectins and environmental hazards in relation to the incidence of chondroid pulmonary hamartomas.
This prospective study includes 103 cases of chondroid pulmonary hamartomas, resected over a period of nearly six years. Genes encoding proteins of the high motility group (HMGI-C, (Y), chromosomes 12q15 and 6p21) were analyzed cytogenetically. Furthermore, we examined the expression of growth-regulatory markers, including galectins-1, -3, -8, heparin-binding lectin (HBL), calcyclin (S100A6) and macrophage migration inhibitory factor (MIF), as well as that of Ki-67 (MIB-1). Syntactic structure analysis was applied to automated classification of stained histological slides and for the detection of topological properties in hamartomas and disease-free lung. These data were set in relation to clinical features, including environmental hazards, smoking habit, and the occurrence of heart-lung disease. Men and women contributed to the study in 61 and 42 cases, respectively. Smoking was frequent (75% men and 54% women), with a mean tobacco consumption of 36 pack years. Aberrations affecting exclusively the HMGI-C gene and the HGMI(Y) gene were seen in 46 cases (44.7%) and in 22 cases (21.3%), respectively. Both genes were affected in only one case. Abnormalities most frequently occurred in chromosomal bands 6p12 and 12q14. Genetic aberrations were significantly increased in men exposed to environmental (occupational) risk factors, excluding smoking (p < 0.05), and in tumors larger than average hamartomas. There were significant differences in staining profiles, particularly for calcyclin and MIF. The mean proliferation index was Nv = 9.9 +/- 6.4%; structural entropy was similar in all markers applied. Owing to their remarkably high values (from 142 to 148), these data were in contrast to a low current of entropy seen in most markers applied. The staining profile identified several markers that delimited cell positivity from normal parenchymal cells. These results contribute to the definition of biochemical characteristics in hamartomas and can be useful for distinguishing them from chronic degenerative disorders.
Kayser
Klaus
K
UICC Telepathology Consultation Center, Institute of Pathology, Charité, Humboldt University, Berlin, Germany. klkayser@lung.de
Dünnwald
Delia
D
Kazmierczak
Bernd
B
Bullerdiek
Jörn
J
Kaltner
Herbert
H
Zick
Yehiel
Y
André
Sabine
S
Gabius
Hans-Joachim
HJ
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D018797:Cell Cycle Proteins; D002869:Chromosome Aberrations; D019277:Entropy; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D037161:Galectins / Q000378:metabolism*; D006222:Hamartoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019044:Image Cytometry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008171:Lung Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects
D001426:Bacterial Proteins; D015415:Biomarkers; D018797:Cell Cycle Proteins; D037161:Galectins; C104637:HmcI protein, Haemophilus influenzae; D019394:Ki-67 Antigen; D037102:Lectins; D008263:Macrophage Migration-Inhibitory Factors; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C085529:heparin-binding lectin; C055351:S100A6 protein, human