title: Overexpression of PIK3CA is associated with lymph node metastasis in esophageal squamous cell carcinoma.
abstract: The genomic region containing PIK3CA was found to be amplified in esophageal squamous cell carcinoma (ESCC) tissue. PIK3CA at 3q26, which encodes the p110alpha 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.
authors.affiliation: Department of Surgery for Organ Function and Biological Regulation, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan. ichiro@nms.ac.jp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Akagi
authors.forename: Masao
authors.initials: M
authors.lastname: Miyashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Makino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nomura
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Hagiwara
authors.forename: Ken
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Cho
authors.forename: Takuya
authors.initials: T
authors.lastname: Mishima
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishibashi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takizawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tajiri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human