Overexpression of PIK3CA is associated with lymph node metastasis in esophageal squamous cell carcinoma

Abstract

Abstract. The genomic region containing PIK3CA was found to be amplified in esophageal squamous cell carcinoma (ESCC) tissue. PIK3CA at 3q26, which encodes the p110· catalytic subunit of phosphatidylinositol (PI) 3-kinase, is a unique intracellular signal transducer characterized by its lipid substrate specificity. In order to characterize PIK3CA in ESCC, we investigated hot-spot mutations in exons 1, 9 and 20, the copy number gain, the expression levels of mRNA and protein. Analysis in exon 9 of the PIK3CA gene revealed mutation in 7.7% (4 of 52) of ESCC samples. No mutation was detected in either exon 1 or exon 20. Copy number amplifications of PIK3CA were found in 12 of the 45 patients (26.7%). PIK3CA mRNAs were examined in 37 ESCC patients as determined by quantitative RT-PCR and the mean mRNA level of PIK3CA in ESCC tissues was 2.61-fold higher compared with that in corresponding non-tumorous esophageal epithelia (P<0.001). Immunohistochemically, positive immunoreaction for PIK3CA was detectable in 33 of 66 (50.0%) ESCC cases, while it was not detectable in the remaining 33 cases. Furthermore, comparing the cases with negative staining with those with positive staining for PIK3CA, the presence of node metastasis was significantly correlated with those with positive staining (P<0.05). This study is the first report providing comprehensive analysis of PIK3CA expression in ESCC. These results indicate that PIK3CA may play a crucial role in the development of ESCC and serve as an indicator for lymph node metastasis.

Aloe-emodin suppresses esophageal cancer cell TE1 proliferation by inhibiting AKT and ERK phosphorylation

“…In the present study, ERK and AKT were activated in EC cell lines, including TE1, Eca109 and KYSE 140, which implies that these two activation pathways are important in esophageal tumorigenesis and development. Previous studies have also indicated that both MEK/ERK and PI3K/AKT signaling are activated in ESCC (8,48,49). Therefore, blocking these two pathways is a promising strategy for EC treatment and chemoprevention.…”

“…Accumulating evidence indicates that numerous molecular changes are associated with EC tumorigenesis, including epidermal growth factor receptor (EGFR) amplification, phosphoinositide 3-kinase, catalytic subunit alpha (PIK3CA) amplification and mutation (8)(9)(10), and phosphatase and tensin homolog (PTEN) mutation or loss (11,12). Alteration of these molecular events contributes to downstream pathway activation (8)(9)(10)(11)(12).…”

“…Alteration of these molecular events contributes to downstream pathway activation (8)(9)(10)(11)(12). The phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase kinase (MEK)/ERK signaling pathways are two important pathways that can be activated by EGFR amplification and PTEN loss, which may ultimately lead to tumorigenesis (13).…”

Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199)

“…Results were analyzed using a 2 tiered (0/1 + vs. 2/3+) and 4 tiered (0 vs. 1vs. 2 vs. 3 +) categorical approach [19].…”

PIK3CA Mutation Is Associated with a Favorable Prognosis among Patients with Curatively Resected Esophageal Squamous Cell Carcinoma

“…10). In studies of ESCC, PIK3CA mutation has been detected in 2.2% to 11.8% of analyzed cases (11)(12)(13)(14), and its prognostic role has been still unknown. Previous studies in large numbers of cases (more than 200) have shown that PIK3CA mutations are associated with unfavorable prognosis in patients with colorectal (15)(16)(17)(18)(19) or lung cancer (20).…”