Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar
Malignant salivary gland tumors (MSGT) are rare, heterogeneous lesions with a variable prognosis. Mammalian cells are subject to thousands of spontaneous changes in the deoxyribonucleic acid (DNA) molecule. The apuric or apyrimidic endonuclease protein 1 (APE1) and the X-ray crossover complementa...
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| Formato: | Dissertação |
| Idioma: | pt_BR |
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/28977 |
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| Resumo: | Malignant salivary gland tumors (MSGT) are rare, heterogeneous lesions with a variable
prognosis. Mammalian cells are subject to thousands of spontaneous changes in the
deoxyribonucleic acid (DNA) molecule. The apuric or apyrimidic endonuclease protein 1
(APE1) and the X-ray crossover complementation protein 1 (XRCC1) are two important
components of the base excision repair pathway (BER), and the complementation factor
protein F of the xeroderma pigmentosum (XPF), the nucleotide excision repair pathway
(NER). This study analyzed the immunohistochemical expression of APE1 and XRCC1
proteins of the BER pathway, and XPF of the NER pathway, in a sample of primary tumors of
acinar cell carcinoma (ACC), polymorphic adenocarcinoma (PAC), adenoid cystic carcinoma
(AdCC) and mucoepidermoid carcinoma (MEC). A total of 62 MSGT were included and
submitted to immunohistochemistry against the selected antibodies, corresponding to 14
ACC, 15 PAC, 16 AdCC, and 17 MEC. The tissue sections were subjected to
immunohistochemistry for APE1, XRCC1 and XPF. The cells of the tumor parenchyma were
quantitatively evaluated, using photomicrographs of 5 fields (in 400x magnification), by a
single evaluator. Immunoreactive cells were those with brownish color in the nucleus and/or
nucleus/ cytoplasm, regardless of intensity. Immunomarked and negative cells were counted
in the 5 fields, establishing the percentage of positive cells in relation to the total number of
cells counted. In addition, it was established whether the nucleus or nucleus/cytoplasm ratio,
inferring whether the location was predominantly uni or bicompartmental. Statistical tests
included Fisher's exact, Mann-Whitney, Kruskal-Wallis, Spearman's correlation, as well as
the log-rank for comparison of the overall survival built through Kaplan-Meier method.
Significance was set at p<0.05. All selected MSGT scored for APE1, XRCC1 and XPF. There
was no difference between the expression of APE1 and XPF among the studied tumors. For
XRCC1, however, there was a significant difference between PAC and MEC (p=0.032).
Nuclear labeling of APE1 was statistically higher in the selected MSGT (p<0.0001). There
was a statistical relationship between APE1 and T1-T2 tumors in the AdCC (p=0.006), as
well as an increase in XPF in patients with MEC over 60 years (p=0.015) and AdCC in a
minor salivary gland (p=0.012), although reduced in patients treated with surgery associated
with adjuvant therapy in ACC and AdCC (p=0.036 and p=0.020, respectively). The low
expression of XRCC1 in the nucleus (p=0.028) or the expression of concomitant XRCC1 in
the nucleus and cytoplasm (p=0.017) were associated with a lower overall 5-year survival
rate. Finally, the Spearman correlation test demonstrated a positive correlation between APE
and XRCC1 in all MSGT analyzed, although the correlation among the three proteins (APE1,
XRCC1 and XPF) was observed only in AdCC and MEC (p<0.05). This study demonstrated
high expression of the repair proteins APE1, XRCC1 and XPF in ACC, PAC, AdCC, and
MEC, which may suggest regulatory activity related to the genotoxic control of these proteins
in MSGT. |
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