Growth vs. DNA strand breaks in Hodgkin's disease: impaired proliferative ability of Hodgkin and Reed-Sternberg cells.
We re-appraised the cell renewal pattern in Hodgkin's disease (HD), considering that most, though not all, Hodgkin/Reed-Sternberg (H-RS) cells exhibit abortive mitoses and that a substantial fraction of these exhibits DNA damage suggestive of imminent or actual cell death. Using combined immunohistochemistry and in situ end-labeling to detect strand breaks, the percentage per case of CD30+ (mainly H-RS) cells with DNA fragmentation (DNA fragmentation index [DFI]) was estimated. For each case, we registered the mitotic index (MI) of CD30+ cells and the percentage of Ki-67+ atypical large cells. To quantify the sum of our parameters for mitosis, whether successful or not, and DNA damage, we introduced the kinetic event index (KEI = MI + DFI). Only DFI and KEI distinguished significantly between mixed cellularity and nodular sclerosis HD. The values for MI and DFI, and therefore for KEI, CD30+ and CD30- small lymphoid cells were proportional. The percentages of Ki-67+ large atypical cells (median 50%) did not correlate significantly with either MIs or DFIs of CD30+ cells. Cluster analysis revealed the existence, independent of histological subtype, of 2 large groups of HD with different KEIs. Our findings suggest that cell deletion plays an important role in HD. Further, it appears that proliferation-associated antigens in H-RS cells do not reflect successful cell production in this disorder.
Spina
D
D
Institute of Pathologic Anatomy and Histology, University of Siena, Italy.
Leoncini
L
L
Close
P
P
Megha
T
T
Pacenti
L
L
Tosi
P
P
Pileri
S
S
Sabattini
E
E
Kraft
R
R
Laissue
J
J
Cottier
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D002455:Cell Division; D004249:DNA Damage; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology*; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016539:Reed-Sternberg Cells / Q000473:pathology*
D017730:Ki-1 Antigen