PMID- 13679452
OWN - NLM
STAT- MEDLINE
DCOM- 20040429
LR  - 20151119
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 16
IP  - 9
DP  - 2003 Sep
TI  - Cyclin D3 immunoreactivity in gastrointestinal stromal tumors is independent of 
      cyclin D3 gene amplification and is associated with nuclear p27 accumulation.
PG  - 886-92
AB  - An abnormal expression of cyclin D3, a key regulator of the cell cycle, has been 
      documented in a variety of human malignancies, and the cyclin D3 gene, mapping to 
      6p21, may be deregulated in human tumors as a result of the t(6;14)(p21.1;q32.3) 
      translocation or gene amplification. In the current study, we for the first time 
      investigated by immunohistochemistry and fluorescence in situ hybridization 
      (FISH) the prevalence of cyclin D3 abnormalities in gastrointestinal stromal 
      tumors (GISTs), comparing the results with traditional pathological 
      characteristics, p27 immunoreactivity (IR), and Ki-67 labeling index (LI). All 
      the tumors showed nuclear cyclin D3 IR, with a percentage of immunostained 
      neoplastic cells ranging from 10 to 95% (mean, 67.3 +/- 22.9%). In 4 (40%) of the 
      10 cases analyzed by FISH, cyclin D3 extrasignals were detected. Cohybridization 
      with probes specific for the centromeric region and the long arm of chromosome 6 
      indicated trisomy in one case, whereas in the remaining three cases the pattern 
      was highly suggestive for the occurrence of an isochromosome 6p. There was no 
      association between the cyclin D3 gene copy number and IR for the encoded 
      protein. Cyclin D3 IR was positively associated with p27 IR (P =.004) but not 
      with Ki-67 LI or tumor malignant potential. On the contrary, p27 IR was inversely 
      associated with Ki-67 LI (P =.004) and was more prevalent in tumors of low or 
      intermediate malignant potential, though at a borderline level of statistical 
      significance (P =.066) only. These data suggest that cyclin D3 expression in 
      GISTs is independent of gene amplification and that this protein may be involved 
      in the pathogenesis of GISTs by counteracting the inhibitory activities of p27.
FAU - Pruneri, Giancarlo
AU  - Pruneri G
AD  - Division of Pathology, European Institute of Oncology, Milan, Italy.
FAU - Mazzarol, Giovanni
AU  - Mazzarol G
FAU - Fabris, Sonia
AU  - Fabris S
FAU - Del Curto, Barbara
AU  - Del Curto B
FAU - Bertolini, Francesco
AU  - Bertolini F
FAU - Neri, Antonino
AU  - Neri A
FAU - Viale, Giuseppe
AU  - Viale G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CCND3 protein, human)
RN  - 0 (Cyclin D3)
RN  - 0 (Cyclins)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (p27 antigen)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*analysis
MH  - Cell Cycle/genetics
MH  - Cell Nucleus/metabolism
MH  - Chromosomes, Human, Pair 6
MH  - Cyclin D3
MH  - Cyclins/*genetics/*metabolism
MH  - Female
MH  - Gastrointestinal Neoplasms/*metabolism/pathology
MH  - Gene Amplification
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Ki-67 Antigen/metabolism
MH  - Male
MH  - Middle Aged
MH  - Proliferating Cell Nuclear Antigen/*metabolism
EDAT- 2003/09/19 05:00
MHDA- 2004/04/30 05:00
CRDT- 2003/09/19 05:00
PHST- 2003/09/19 05:00 [pubmed]
PHST- 2004/04/30 05:00 [medline]
PHST- 2003/09/19 05:00 [entrez]
AID - 10.1097/01.MP.0000085026.38856.B9 [doi]
PST - ppublish
SO  - Mod Pathol. 2003 Sep;16(9):886-92. doi: 10.1097/01.MP.0000085026.38856.B9.