Comparative topoisomerase IIa and ki 67 protein expression in papillary thyroid carcinoma based on tissue microarrays and image analysis.
OBJECTIVE
Topoisomerase II alpha (Topo IIa gene location 17q21) is a nucleic enzyme involved in the DNA replication, transcription and chromosome topological formation. Topo IIa inhibition strategies include specific chemotherapeutic agents such as anthracyclines. Our aim was to investigate potential protein alterations of the enzyme comparing them to ki 67 proliferation marker expression in papillary thyroid carcinoma (PTC).


METHODS
Using tissue microarray (TMA) technology, 50 specimens consisting of histologically confirmed PTCs (n=20), multi-nodular goiters (n=20) and also normal thyroid epithelia (n=10) were cored and re-embedded in the final paraffin block. Immunohistochemical analysis was performed using monoclonal anti-Topo IIa and anti-ki 67 (MIB-1) antibodies. Digital image analysis assay was also applied for the evaluation of the protein expression results (Nuclear Labeling Index-NLI).


RESULTS
Topo IIa and ki 67 proteins were overexpressed in 4/20 (20%) and 14/20 (70%) cases, respectively. Concerning multi-nodular goiters, overexpression was observed in 2/20 and 4/20 specimens, respectively. Statistical association was assessed correlating ki 67 expression to pathology type, capsular invasion and also to vascular infiltration (p=0.001, p=0.008, and p=0.012, respectively). Topo IIa protein expression was strongly correlated only to capsular invasion (p=0.004). Overall expression of the examined markers demonstrated a medium concordance (kappa=0.27), but a strong association (p=0.001).


CONCLUSIONS
Topo IIa and also ki 67 overexpression are correlated to an aggressive phenotype in PTC. Topo IIa overexpression maybe is a reliable marker for a rational application of targeted chemotherapeutic strategies in some subgroups of patients.
Manaios
L
L
Department of Surgery, "Bioclinic", Athens, Greece.
Tsiambas
E
E
Alevizaki
M
M
Karameris
A
A
Alexopoulou
D
D
Lambropoulou
S
S
Moreas
H
H
Kravvaritis
C
C
Fotiades
P P
PP
Goula
K
K
Patsouris
E
E
Athanassiou
A E
AE
Koutras
D
D
Katsilambros
N
N
D000951:Antigens, Neoplasm / Q000032:analysis*; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000473:pathology*; D049109:Cell Proliferation; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000473:pathology*; D046888:Tissue Array Analysis / Q000379:methods*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D004250:DNA Topoisomerases, Type II