Loss of SFRP1 expression is associated with aberrant beta-catenin distribution and tumor progression in mucoepidermoid carcinoma of salivary glands.
BACKGROUND
Cytoplasmic and nuclear accumulation of beta-catenin in mucoepidermoid carcinoma (MEC) is frequently noted, but the mechanism is unknown.


METHODS
The methylation status of adenomatous polyposis coli (APC) and secreted frizzled-related proteins (SFRPs) was examined by methylation-specific polymerase chain reaction (MSP) assay. The association of SFRP1, beta-catenin, and cyclin D1 expression in MEC was evaluated by immunohistochemical staining.


RESULTS
A high percentage of methylation in APC and the SFRP genes was found in MEC compared with adjacent normal tissues, in which SFRP1 (58.6%) was the most frequent methylated gene. Moreover, abundant expression of SFRP1 was noted in normal tissues, whereas reduced SFRP1 expression was detected in 71.7% (33/46) of MECs. There was significant association between methylation and reduced expression of SFRP1. Cytoplasmic/nuclear (C/N) beta-catenin and high cyclin D1 expression were found in 13/55 (23.6%) and 36/55 (65.5%) of cases, respectively. There was significant correlation between C/N beta-catenin expression and reduced SFRP1 expression (P = 0.009). In addition, SFRP1 and beta-catenin expression correlated with tumor malignancy index such as tumor grade and stage. Overall patient survival was significantly worse in patients with reduced SFRP1 and C/N beta-catenin expression (P = 0.009 and P = 0.002, respectively).


CONCLUSIONS
Methylation of the SFRP1 gene was the major cause of reduced SFRP1 expression. Reduced SFRP1 led to C/N accumulation of beta-catenin and was associated with tumor malignancy. Therefore, examination of SFRP1 expression and beta-catenin location could be useful predictors of tumor progression and prognosis in patients with MEC.
Lee
Chien-Hsing
CH
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Hung
Yi-Jen
YJ
Lin
Chih-Yuan
CY
Hung
Pei-Hsin
PH
Hung
Hsing-Wen
HW
Shieh
Yi-Shing
YS
D011125:Adenomatous Polyposis Coli / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018277:Carcinoma, Mucoepidermoid / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008745:Methylation; D009385:Neoplastic Processes; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D051176:beta Catenin / Q000378:metabolism*; D000094742:Secreted Frizzled-Related Proteins
D014408:Biomarkers, Tumor; D019938:Cyclin D1; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051176:beta Catenin; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins