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Loss of SFRP1 Expression is Associated with Aberrant β-Catenin Distribution and Tumor Progression in Mucoepidermoid Carcinoma of Salivary Glands

  • Translational Research and Biomarkers
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Cytoplasmic and nuclear accumulation of β-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, β-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) β-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 β-catenin expression and reduced SFRP1 expression (P = 0.009). In addition, SFRP1 and β-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 β-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 β-catenin and was associated with tumor malignancy. Therefore, examination of SFRP1 expression and β-catenin location could be useful predictors of tumor progression and prognosis in patients with MEC.

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Acknowledgment

This work was supported by grants DOH98-TD-I-111-TM011-001, NHRI-EX97-9602BC, NSC96-2628-B-016-007-MY3, TSGH-C98-26, and DOD98-21-02, Taiwan.

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Authors and Affiliations

  1. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

    Chien-Hsing Lee MD

  2. Departments of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan

    Chien-Hsing Lee MD & Yi-Jen Hung MD

  3. Departments of Surgery, Tri-Service General Hospital, Taipei, Taiwan

    Chih-Yuan Lin MD

  4. Departments of Dentistry, Tri-Service General Hospital, Taipei, Taiwan

    Pei-Hsin Hung MD, Hsing-Wen Hung MD & Yi-Shing Shieh MD, PhD

  5. School of Dentistry, National Defense Medical Center, Taipei, Taiwan

    Yi-Shing Shieh MD, PhD

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  1. Chien-Hsing Lee MD
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  2. Yi-Jen Hung MD
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Correspondence to Yi-Shing Shieh MD, PhD.

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Lee, CH., Hung, YJ., Lin, CY. et al. Loss of SFRP1 Expression is Associated with Aberrant β-Catenin Distribution and Tumor Progression in Mucoepidermoid Carcinoma of Salivary Glands. Ann Surg Oncol 17, 2237–2246 (2010). https://doi.org/10.1245/s10434-010-0961-z

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  • DOI: https://doi.org/10.1245/s10434-010-0961-z

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