title: Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma.
abstract: DNA amplification is one of the mechanisms to activate genes that are implicated in neoplastic transformation and gain of chromosome band 3q26 is a common event in squamous cell carcinomas. The aim of the present work was to identify the specific target gene from four candidates (MDS1, PRKCI, ECT2, and PIK3CA) located on 3q26 amplification in esophageal squamous cell carcinomas (ESCCs). To assess the prevalence of copy number gains of putative genes, fluorescence in situ hybridization (FISH) was applied on 108 ESCCs and 9 ESCC cell lines. Our data showed that MDS1 and PRKCI were more frequently gained. Positive correlation was found only for PRKCI between amplification and tumor size (P = 0.043), lymph node metastasis (P = 0.015) and clinical stage (P = 0.002). PRKCI gene amplification was highly correlated with protein overexpression (P = 0.009), suggesting that gene amplification is one important mechanism involved in PRKCI overexpression. To investigate further the role of PRKCI alteration in esophageal tumors, a tissue microarray containing samples from 180 ESCCs was used for immunohistochemistry analysis. Statistical analysis revealed that PRKCI overexpression was correlated with lymph node metastasis (P = 0.002) and higher stage (P = 0.004). Performing multivariate logistic regression analysis, a significant association between PRKCI overexpression and presence of lymph node metastasis was found, which was independent of T-stage of the primary tumors (P = 0.004). Our results indicate that PRKCI is an attractive target in the 3q26 amplicon and that it may serve as a molecular marker for metastasis and occult advanced tumor stages in ESCC.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Chu
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Luo
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Feng
authors.forename: Zhi-Zhou
authors.initials: ZZ
authors.lastname: Shi
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
authors.forename: Qi-Min
authors.initials: QM
authors.lastname: Zhan
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000099293:Protein Kinase C-lambda
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda