Mutational and Immunohistochemical Study of the PI3K/Akt Pathway in Papillary Thyroid Carcinoma in Greece

Abstract

PI3K/Akt signaling pathway plays critical role in many cell processes. There is indication that enhanced activation of PI3K/Akt cascade is implicated in thyroid tumors. Aim of this study was to evaluate the mutational status and expression of PI3K/Akt pathway mediators in papillary thyroid carcinoma in Greece. We evaluated the presence of mutations in PIK3CA (exons 9 and 20), AKT1 (exons 6-11), AKT2 (exons 6-11), AKT3 (exons 5-10), PTEN (exons 3-8), and PDPK1 (exons 4-10) genes in 83 papillary thyroid carcinomas by DNA sequencing. The expression levels of phospho-Akt and insulin-like growth factor I receptor (IGF-IR) were evaluated by immunohistochemistry. PIK3CA mutations were found in three samples. The analysis of AKT1 revealed one silent mutation in exon 9 (G726A) in 16 samples. One specimen carried an AKT3 mutation. One missense mutation was found in one sample in PTEN. No mutations were found in AKT2 and PDPK1. Increased levels of phosphorylated total Akt and IGF-IR were identified in some papillary cancers. Our findings indicate that PI3K/Akt signaling pathway is activated in some papillary tumors. However, mutations in genes coding most mediators of the pathway have not been proven to be the major modus of enhanced activation. These data suggest a potential role for PI3K/Akt-mediated signaling in papillary thyroid tumors.

Evaluation of PTEN, PI3K, MTOR, and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma

“…In a study conducted by Sozopoulos et al ., the mutational status and the expression of mediators of the PI3K/Akt pathway were examined in PTC both genetically and immunohistochemically. Although these genetic alterations primarily manifest as phosphorylation and activation of Akt, increased active phosphorylated (p)-Akt was not detected using immunohistochemical methods [19]. …”

Cribriform-morular variant of papillary thyroid carcinoma: a study of 3 cases featuring the PIK3CA mutation

“…The PI3K/Akt signaling pathway plays major roles in several cellular events, including growth, proliferation, and apoptosis [7,16]. The activation of this pathway leads to tumorigenesis, including thyroid carcinoma [16,25,26]. Together with β-catenin signaling, PI3K signaling may indirectly augment cell differentiation by promoting cell proliferation and recruiting more cells [27,28], which may lead to the multiple growth patterns observed in CMV-PTC.…”

“…A PIK3CA mutation can occur in some cases of recurrent or metastatic disease from aggressive, poorly differentiated thyroid carcinomas [30]. However, the PIK3CA mutation is relatively infrequent (1.9%-3.6%) in PTCs and does not seem to be a major genetic event in PTCs in general [25,26]. However, we found that all 3 cases of CMV-PTC harbored the same mutation in exon 9, codon 545, of the PIK3CA gene (p.E545A).…”

Comparative Evaluation of Strategies for Quantifying Signaling Pathway Proteins in Ewing Sarcoma

“…35 While our immunohistochemistry assays for phospho-AKT and phospho-P70S were not successful, other studies have been able to do so using formalin fixed paraffin embedded tissue from other tumor types. 36,37 This may be due either to biologic differences of the tumor type and/or differences in laboratory techniques. In addition, our sample size and retrospective study design make it difficult to determine the true correlation between quantitative methods of expression and standard IHC.…”