Changes in the balance between proliferation and apoptosis during the progression of malignancy in thyroid tumours.
The aim of this study was to gain better insight into molecular changes which reflect disturbances in the balance between proliferation and apoptosis during progression of thyroid malignancy from papillary microcarcinoma (PMC) via clinically manifest papillary carcinoma (PTC) to anaplastic carcinoma (ATC). The apoptosis related molecules (Bcl-2, Bax) and proliferation related marker (PCNA) were analysed immunohistochemically in 120 archival cases comprising PMC (n=34), PTC (n=52) and ATC (n=34). In addition, in situ apoptotic cell death was analysed by the TUNEL method. The average Bcl-2 staining score did not differ between PMC and PTC (p>0.05), but was significantly lower in ATC (p<0.05).The Bax score was higher in PTCs and ATCs than in PMCs (p<0.05). Due to these changes, the Bcl-2/Bax ratio showed a marked decrease from PMC to ATC (p<0.05), while proliferation activity increased significantly from PTC to ATC (p<0.05). Despite high Bax expression, the rate of apoptotic cell death was low in the investigated carcinomas, especially in ATC, i.e. the increase in proliferative activity was not counterbalanced with appropriate cell death. Differences were found in the expression of apoptotic molecules (Bcl-2 and Bax), their ratio (Bcl-2 /Bax) and in the rate of apoptotic cell death and proliferative activity between PMC, PTC and ATC, indicating that disturbances in the balance between apoptosis and proliferation, in favour of the latter, occur gradually during the progression of malignancy in thyroid tumours.
Cvejic
D
D
Institute for the Application of Nuclear Energy - INEP, University of Belgrade, Zemun - Belgrade, Serbia. dubravka@inep.co.yu
Selemetjev
S
S
Savin
S
S
Paunovic
I
I
Tatic
S
S
D017209:Apoptosis / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
Ann Oncol. 2000 Sep;11(9):1083-9
11061600
Curr Biol. 1993 Jun 1;3(6):391-4
15335741
Cancer. 1978 Jun;41(6):2267-75
657091
Surgery. 2006 Dec;140(6):899-905; discussion 905-6
17188136
Eur J Histochem. 2008 Jul-Sep;52(3):153-62
18840555
Nature. 1991 Jun 6;351(6326):453-6
2046748
Neoplasma. 2001;48(4):299-301
11712682
Biochim Biophys Acta. 2004 Mar 1;1644(2-3):229-49
14996506
Am J Med. 1994 Nov;97(5):418-28
7977430
Eur J Histochem. 2007 Oct-Dec;51(4):291-300
18162459
J Cell Biol. 1994 Jan;124(1-2):1-6
8294493
Adv Anat Pathol. 2006 Mar;13(2):69-75
16670460
Endocr Pathol. 2003 Fall;14(3):183-91
14586064
Cancer. 1997 Feb 1;79(3):564-73
9028369
Crit Rev Oncol Hematol. 1995 Feb;18(2):67-102
7695829
J Pathol. 1994 Apr;172(4):337-42
8207614
Br J Cancer. 1996 Jan;73(2):139-43
8546897
Histopathology. 1998 Jan;32(1):35-42
9522214
Pathol Int. 2005 Nov;55(11):694-702
16271081
Acta Chir Belg. 2005 Nov-Dec;105(6):644-8
16438077
J Cell Mol Med. 2003 Jul-Sep;7(3):249-57
14594549
J Clin Endocrinol Metab. 2006 Jun;91(6):2171-8
16478817
Arch Otolaryngol Head Neck Surg. 1988 Jan;114(1):40-4
3334817
Surg Today. 1999;29(3):204-8
10192728
Endocr Pathol. 1993 Dec;4(4):215-221
32370456
Int J Cancer. 2001 Jun 15;92(6):805-11
11351299
Virchows Arch. 1997 Feb;430(2):125-30
9083515
Exp Oncol. 2004 Dec;26(4):282-6
15627060
Thyroid. 2000 Feb;10(2):117-22
10718547
Eur J Surg Oncol. 2006 Dec;32(10):1144-8
16872798
Pathology. 2008 Aug;40(5):475-80
18604733
Genes Dev. 1999 Aug 1;13(15):1899-911
10444588
J Clin Endocrinol Metab. 1996 Jul;81(7):2726-30
8675602