Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma.
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.
Yang
Yi-Ling
YL
State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Chu
Jia-You
JY
Luo
Man-Li
ML
Wu
Yu-Peng
YP
Zhang
Yu
Y
Feng
Yan-Bin
YB
Shi
Zhi-Zhou
ZZ
Xu
Xin
X
Han
Ya-Ling
YL
Cai
Yan
Y
Dong
Jin-Tang
JT
Zhan
Qi-Min
QM
Wu
Min
M
Wang
Ming-Rong
MR
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
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda