TWIST and p-Akt immunoexpression in normal oral epithelium, oral dysplasia and in oral squamous cell carcinoma

Abstract

Objectives: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. Study design: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. Results: Kruskal-Wallis and Dunn’s post tests revealed a significant difference in TWIST and p-Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson’s correlation test. Conclusions: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages. Key words: Oral cancer, oral leukoplakia, dysplasia, immunohistochemistry.

Immunohistochemical Analysis of the Activation Status of the Akt/mTOR/pS6 Signaling Pathway in Oral Lichen Planus

“…Although the mechanisms and the significance of this compartmentalization are largely unknown, previous investigations have shown variable distribution of p-Akt in different cellular compartments of oral premalignant and malignant lesions indicating that p-Akt localization may be related to differences in activity [10, 11]. In addition, differential subcellular (nuclear vs. cytoplasmic) p-Akt localization has been reported in other types of cancer and, as suggested, may play a significant role in determining its function [12–15].…”

“…Regarding the localization of immunostaining, Pontes et al [10] reported that p-Akt was expressed mainly in both cytoplasmic and nuclear compartments, although restricted staining in either the nucleus or the cytoplasm was also occasionally observed. de Freitas Silva et al [11] also evaluated p-Akt immunohistochemical levels in oral lesions and reported a significant increase in OL and OSCC compared to NM; no significant differences among OL cases with different degrees of dysplasia were noted. With regard to localization, de Freitas Silva et al [11] reported that NM and OL cases showed p-Akt immunoreactivity limited to the nucleus, whereas OSCC cells expressed both nuclear and cytoplasmic immunostaining.…”

“…de Freitas Silva et al [11] also evaluated p-Akt immunohistochemical levels in oral lesions and reported a significant increase in OL and OSCC compared to NM; no significant differences among OL cases with different degrees of dysplasia were noted. With regard to localization, de Freitas Silva et al [11] reported that NM and OL cases showed p-Akt immunoreactivity limited to the nucleus, whereas OSCC cells expressed both nuclear and cytoplasmic immunostaining. The authors suggested that p-Akt may participate in the multistep process of oral carcinogenesis and may be associated with TWIST expression, a molecule involved in epithelial-mesenchymal transition [11].…”

HS-173, a novel PI3K inhibitor suppresses EMT and metastasis in pancreatic cancer

“…Vichalkovski et al have reported that activation of AKT upregulated the expression of Twist, subsequently decreasing chemotherapy-induced DNA damage, and inhibiting apoptosis [21]. Moreover, phosphorylated AKT is positively correlated with the high level of Twist as well as low expression of Ecadherin in oral squamous cell carcinoma [22]. In addition, the treatment of AKT inhibitor decreased the expression of Snail and Twist [23, 24] and eventually promoting the expression of Ecadherin, reducing the expression of Vimentin; restored the polygonal shape of cells, and stimulated the mesenchymal-epithelial transition (MET).…”

Acquired resistance to BRAF inhibition induces epithelial-to-mesenchymal transition in BRAF (V600E) mutant thyroid cancer by c-Met-mediated AKT activation

“…That is, intranuclear accumulation of p-AKT and nuclear exclusion of p27 to the cytoplasm was directly associated with the invasiveness of thyroid cancer cells with acquisition of mesenchymal phenotype, thereby suggesting AKT activation is involved in direct induction of EMT. Furthermore, this has been suggested by many others where levels of Snail and Twist and AKT phosphorylation were also positively correlated in oral squamous cell carcinoma and prostate carcinoma [25–27]. In head and neck squamous cell carcinoma, PI3K/AKT activation degrades E-cadherin and promotes cell invasion and migration [28, 29].…”