masterThesis
Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior
Fecha
2021-06-25Registro en:
MORAIS, Hannah Gil de Farias. Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior. 2021. 125f. Dissertação (Mestrado em Ciências Odontológicas) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2021.
Autor
Morais, Hannah Gil de Farias
Resumen
Epithelial-mesenchymal transition (EMT) is a biological process that has been widely studied
in oral squamous cell carcinoma (SCC), however, it is still rarely evaluated in lip
carcinogenesis. The aim of this study was to investigate the immunoexpression of E-cadherin,
α-SMA, TGF-β and Snail proteins in actinic cheilitis (AC) histopathologically diagnosed as
epithelial dysplasia, and in lower lip squamous cell carcinoma (LLSCC). The
immunoexpression of E-cadherin, α-SMA, TGF-β and Snail was semiquantitatively analyzed
in 54 cases of ACs and 49 LLSCCs. Aiming at association of immunohistochemical findings
with clinicopathological variables and overall (OS) and disease-free (DFS) survival rates, cases
were classified into low expression and high expression categories. There were no statistically
significant associations with any of the proteins analyzed with the degree of severity of
epithelial dysplasia in ACs (p > 0.05). Immunohistochemical analysis in LLSCCs revealed that
low membrane expression of E-cadherin in tumor front was significantly associated with
LLSCCs with ≥5 buds (p = 0.005) and high score for both BD model (p = 0.009) and the
proposed model by Dourado et al. (2020) (p = 0.038), however, no significant associations were
observed between immunoexpression of this protein and clinical parameters (p > 0.05).
Significant associations were also found between low expression of α-SMA with LLSCCs in
clinical stages TNM I/II (p = 0.05), low depth of invasion (p = 0.006), < 5 buds (p = 0.027) and
score of low/intermediate risk, while high expression of this protein was associated with the
outcome of death (p = 0.009). Significant associations were also found between α-SMA
network/spindle immunostaining pattern with LLSCCs in TNM stages III/IV (p = 0.031), with
high depth of invasion (p = 0.002), ≥5 buds (p = 0.027), high BD risk score (p = 0.001) and
death outcome (p = 0.015). Regarding the TGF-β protein, statistically significant associations
were noticed between its low expression in tumor buds with absence of lymph node metastasis
(p = 0.047) and locoregional recurrence (p = 0.042), however, no significance was observed
with any of morphological parameters (p > 0.05). Immunohistochemical analysis of Snail
protein did not reveal any significant association with clinicopathological parameters (p > 0.05).
The association analysis of protein immunoexpression between the lesions studied revealed
significant results for a high cytoplasmic expression of E-cadherin and LLSCCs (p = 0.001),
high expression of α-SMA and LLSCCs (p < 0.001), low expression of TGF -β and LLSCCs
(p < 0.001) and high expression of Snail and ACs (p = 0.006). Survival analysis revealed a high
expression of α-SMA in tumor front stroma (p = 0.013), a network immunostaining pattern of
this protein (p = 0.046) and high expression of TGF-β in tumor buds (p = 0.043) were
significantly associated with worse OS, and LLSCCs with high expression of α-SMA also had
a higher risk of death (HR = 5.90, p = 0.030). High cytoplasmic expression of TGF-β in tumor
buds was significantly associated with both worse DFS (p = 0.007) and higher risks of negative
outcomes for DFS (HR = 4.44; p = 0.014). The results of present study suggest that although
the immunoexpression of evaluated proteins does not indicate differences in degree of
histopathological severity in ACs, dysregulations of these proteins were identified among the
lesions studied. Furthermore, it was found that LLSCC with more aggressive behavior was
associated with low expression of membrane E-cadherin, high expression of α-SMA and its
network pattern, and low expression of TGF-β in tumor buds.