Expression of Human DNA Topoisomerase II-α in Squamous Cell Carcinoma of the Larynx and Its Correlation With Clinicopathologic Variables

Department of Otolaryngology, Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel.
American Journal of Clinical Pathology (Impact Factor: 3.01). 12/2008; 130(6):934-9. DOI: 10.1309/AJCPROG61USKCBEI
Source: PubMed

ABSTRACT The aggressiveness of laryngeal squamous cell carcinoma (SCC) is unpredictable. Topoisomerase (Topo) II-alpha is an essential nuclear enzyme; its expression rises at the end of the S-G2/M phase and drops at completion of mitosis. This study sought to determine if Topo II-alpha expression can serve as a prognostic factor in laryngeal SCC. Specimens from 56 consecutive patients were immunohistochemically stained for Topo II-alpha, and the number of positive cells in the areas of highest staining was counted in 3 highpower fields (X400) (Topo II-alpha index). Differences in the Topo II-alpha index by the presence or absence of recurrence, tumor stage and grade, and disease course were analyzed statistically. On multivariate Cox regression analysis, the Topo II-alpha index (>70 or < or =70) (P = .008) and tumor grade (P = .034) independently predicted disease-free survival. These findings suggest that high Topo II-alpha expression may be a useful indicator of tumor aggressiveness and poor outcome in laryngeal SCC.

  • Source
    • ". TOP2A has been reported to be over-expressed in pancreatic adenocarcinoma [21], renal medullary carcinomas [22], ovarian cancer [23], acute lymphocytic leukemia [24], colorectal cancer [25], gastric carcinoma [26] and laryngeal squamous cell carcinoma [27]. CCNB2 (Cyclin B2), found commonly upregulated, is a member of the cyclin family, specifically the B-type cyclins. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genes differentially expressed by tumor cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. This study examined the suitability of rodent models of bladder cancer in B6D2F1 mice and Fischer-344 rats to model clinical bladder cancer specimens in humans. Using a global gene expression approach cross-species analysis showed that 13-34% of total genes in the genome were differentially expressed between tumor and normal tissues in each of five datasets from humans, rats, and mice. About 20% of these differentially expressed genes overlapped among species, corresponding to 2.6 to 4.8% of total genes in the genome. Several genes were consistently dysregulated in bladder tumors in both humans and rodents. Notably, CNN1, MYL9, PDLIM3, ITIH5, MYH11, PCP4 and FM05 were found to commonly down-regulated; while T0P2A, CCNB2, KIF20A and RRM2 were up-regulated. These genes are likely to have conserved functions contributing to bladder carcinogenesis. Gene set enrichment analysis detected a number of molecular pathways commonly activated in both humans and rodent bladder cancer. These pathways affect the cell cycle, HIF-1 and MYC expression, and regulation of apoptosis. We also compared expression changes at mRNA and protein levels in the rat model and identified several genes/proteins exhibiting concordant changes in bladder tumors, including ANXA1, ANXA2, CA2, KRT14, LDHA, LGALS4, SERPINA1, KRT18 and LDHB. In general, rodent models of bladder cancer represent the clinical disease to an extent that will allow successful mining of target genes and permit studies on the molecular mechanisms of bladder carcinogenesis.
    American Journal of Translational Research 01/2010; 3(1):8-27. · 3.23 Impact Factor
  • Source
  • Advances in Immunology 02/2004; 83:163-89. DOI:10.1016/S0065-2776(04)83005-0 · 5.53 Impact Factor
Show more


Available from