Correlation between different p53 expression patterns and chromosome 17 imbalances in pancreatic ductal adenocarcinoma based on tissue microarray analysis.
OBJECTIVE
p53 (gene location: 17p13.1) overexpression is a common event in pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignant neoplasm. Although specific mechanisms of p53 gene deregulation have been identified, correlation between p53 expression and chromosome 17 gross numerical imbalances (aneuploidy) are under investigation.


METHODS
Using tissue microarray technology, 60 paraffin-embedded tissue samples of histologically confirmed primary PDACs were cored and re-embedded to the final recipient block. Immunohistochemistry (IHC) for p53 expression and chromogenic in situ hybridization (CISH) for chromosome 17 numerical alterations were performed. Digital image analysis was applied for p53 expression levels evaluation (Nuclear Labelling Index-NLIs).


RESULTS
p53 overexpression was detected in 38/60 (63.3%), whereas chromosome 17 aneuploidy was observed in 21/60 (35%) cases, respectively. Polysomy was identified in 19 cases, whereas monosomy in 2 of them. p53 overall expression was strongly correlated to the stage of the examined tumors (p=0.02). Chromosome aneuploidy was not associated to tumors' stage and grade (p=0.42, p=0.71, respectively). Although overall chromosome 17 centromeric imbalances were not correlated with p53 overexpression (p=0.32), both cases with monosomy demonstrated high expression levels.


CONCLUSIONS
p53 overexpression combined with chromosome 17 numerical imbalances characterizes a significant proportion of PDACs. Because commercially available antip53 antibodies detect mutant and also wild-type protein expression levels, chromosome 17 monosomy maybe is a gross genetic criterion for discriminating them due to point mutation that frequently affects the remaining allele.
Tsiambas
E
E
Department of Pathology, Medical School, University of Athens, Athens, Greece. tsiambasecyto@yahoo.gr
Kravvaritis
C
C
Tsounis
D
D
Salemis
N S
NS
Niotis
A
A
Niotis
T H
TH
Rigopoulos
D N
DN
Karameris
A
A
Athanasiou
A E
AE
Patsouris
E
E
Karakitsos
P
P
D000368:Aged; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016009:Chi-Square Distribution; D002886:Chromosomes, Human, Pair 17; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53