Molecular Diagnostics

British Journal of Cancer (2009) 101, 335–341. doi:10.1038/sj.bjc.6605129 www.bjcancer.com
Published online 16 June 2009

Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer

E Cocco1, S Bellone1, K El-Sahwi1, M Cargnelutti1, F Casagrande1, N Buza2, F A Tavassoli2, E R Siegel3, I Visintin1, E Ratner1, D-A Silasi1, M Azodi1, P E Schwartz1, T J Rutherford1, S Pecorelli4 and A D Santin1

  1. 1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
  2. 2Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
  3. 3Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
  4. 4Division of Gynecologic Oncology, University of Brescia, Brescia, Italy

Correspondence: Dr AD Santin, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Rm. 305 LSOG, 333 Cedar Street, PO Box 208063, New Haven, CT, 06520-8063, USA. E-mail: alessandro.santin@yale.edu

Received 3 March 2009; Revised 8 May 2009; Accepted 18 May 2009; Published online 16 June 2009.

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Abstract

Background:

  

Uterine serous papillary carcinoma (USPC) is a biologically aggressive variant of endometrial cancer. We investigated the expression of Serum Amyloid A (SAA) and evaluated its potential as a serum biomarker in USPC patients.

Methods:

  

SAA gene and protein expression levels were evaluated in USPC and normal endometrial tissues (NEC) by real-time PCR, immunohistochemistry (IHC), flow cytometry and by a sensitive bead-based immunoassay. SAA concentration in 123 serum samples from 51 healthy women, 42 women with benign diseases, and 30 USPC patients were also studied.

Results:

  

SAA gene expression levels were significantly higher in USPC when compared with NEC (mean copy number by RT–PCR=162 vs 2.21; P=0.0002). IHC revealed diffuse cytoplasmic SAA protein staining in USPC tissues. High intracellular levels of SAA were identified in primary USPC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (mug ml-1) had a median (95% CIs) of 6.0 (4.0–8.9) in normal healthy females and 6.0 (4.2–8.1) in patients with benign disease (P=0.92). In contrast, SAA values in the serum of USPC patients had a median (95% CI) of 15.6 (9.2–56.2), significantly higher than those in the healthy group (P=0.0005) and benign group (P=0.0006). Receiver operating characteristics (ROC) analysis of serum SAA to classify advanced- and early-stage USPC yielded an area under the ROC curve of 0.837 (P=0.0024).

Conclusion:

  

SAA is not only a liver-secreted protein but is also a USPC cell product. SAA may represent a novel biomarker for USPC to assist in staging patients preoperatively, and to monitor early-disease recurrence and response to therapy.

Keywords:

uterine serous papillary cancer, serum amyloid A, biomarkers, endometrial carcinoma, tumour markers

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