Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma.
BACKGROUND
The development of esophageal squamous cell carcinoma (ESCC) progresses a multistage process, collectively known as precursor lesions, also called dysplasia (DYS) and carcinoma in situ (CIS), subsequent invasive lesions and final metastasis. In this study, we are interested in investigating the expression of a variety of functional classes of proteins in ESCC and its precursor lesions and characterizing the correlation of these proteins with ESCC malignant progression.


METHODS
Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5gamma2 and SPARC were analyzed using immunohistochemistry on tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well as corresponding normal mucosa. To confirm the immunohistochemical results, three proteins, fascin, CK14 and laminin-5gamma2, which were overexpressed in ESCC on tissue microarray, were detected in 12 ESCC cell lines by Western blot assay.


RESULTS
In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin-5gamma2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I were underexpressed. The abnormalities of these proteins could be classified into different groups in relation to the stages of ESCC development. They were "early" corresponding to mild and moderate DYS with overexpression of fascin, FADD and CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate" to severe DYS and CIS with overexpression of FADD and CK14, and "late" to invasive lesions (ESCC) and to advanced pTNM stage ESCC lesions with overexpression of CK14, laminin-5gamma2 and SPARC.


CONCLUSIONS
Analyzing the protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5gamma2 and SPARC would be valuable to develop rational strategies for early detection of lesions at risk in advance as well as for prevention and treatment of ESCC.
Xue
Li-yan
LY
Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. xueliyan2003@yahoo.com.cn <xueliyan2003@yahoo.com.cn>
Hu
Nan
N
Song
Yong-mei
YM
Zou
Shuang-mei
SM
Shou
Jian-zhong
JZ
Qian
Lu-xia
LX
Ren
Li-qun
LQ
Lin
Dong-mei
DM
Tong
Tong
T
He
Zu-gen
ZG
Zhan
Qi-min
QM
Taylor
Philip R
PR
Lu
Ning
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins