PIK3CA amplification is predictive of poor prognosis in Tunisian patients with nasopharyngeal carcinoma

Abstract

PI3Ks (phosphatidylinositol 3‐kinases) are lipid kinases that regulate signalling pathways involved in cell proliferation, motility, and adhesion. Somatic mutations and amplification of the PIK3CA gene have been reported in various types of human cancers. However, little is known about the frequency and prognosis role of PIK3CA activation in nasopharyngeal carcinoma (NPC). This study was conducted with the aim to screen for PIK3CA mutations in the two hot spot regions (exons 9 and 20) and to investigate for the PIK3CA gene amplification combined with the expression analysis of the phosphorylated Akt (pAkt). We showed that among 88 specimens, none had mutation in the helical domain (exon 9) and only one (1.13%) had mutation in the kinase domain (exon 20). On the other hand, PIK3CA gene amplification was found in 21.6% of cases and was strongly associated with distant metastasis (P = 0.002), lymph node involvement (P = 0.032), and advanced tumor stage (P < 0.001). Moreover, patients with PIK3CA copy number gain have a significant reduced overall survival time (P log rank = 0.02). We concluded that PIK3CA gene amplification is frequent in NPC and occurs in the advanced stage of NPC. Moreover, our finding emphasizes the association of PIK3CA gene amplification with worse prognosis in nasopharyngeal carcinoma. (Cancer Sci 2009); 00: 000–000)

An Orthotopic Model of Metastatic Nasopharyngeal Carcinoma and Its Application in Elucidating a Therapeutic Target That Inhibits Metastasis

“…For example, PI3K amplification with consequent upregulation of Akt activity in primary NPC tumors has been shown to correlate with a poor prognosis resulting from higher rates of metastasis, irrespective of classification based on differentiation status. 41 Similarly, enhanced rates of distant NPC metastasis have been shown to correlate with increased activation of mTOR and not the differentiation status of the primary tumors. 42 Thus, we have more precisely defined a signaling pathway alteration that correlates with metastatic NPC behavior and confirmed that histological characteristics of focal invasion do not necessarily predict tumor dissemination to distant organs.…”

Nasopharyngeal carcinoma: A review

“…49 Both mutations and amplification of PIK3C have been the described and the latter may correlate with poor prognosis. [54][55][56] LMP1 causes endocytosis and nuclear accumulation of EGFR where it acts as a transcription factor to increase proliferation. 57 The transcriptional factor hypoxia-inducible factor 1 alpha (HIF-1alfa) may be overexpressed in NPC and is then associated with distant metastasis and poor survival.…”

Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

“…The phosphoinositide 3-kinases (PI3K) are a group of enzymes involved in diverse cellular functions including cell growth, proliferation, differentiation, motility, survival, and intracellular trafficking [44, 45]. Many of these functions relate to the ability of class I PI3K to phosphorylate and activate a serine/threonine protein kinase B (Akt), in turn regulating cell proliferation and preventing apoptosis [46].…”