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


CONCLUSIONS
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.
Cocco
E
E
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
Bellone
S
S
El-Sahwi
K
K
Cargnelutti
M
M
Casagrande
F
F
Buza
N
N
Tavassoli
F A
FA
Siegel
E R
ER
Visintin
I
I
Ratner
E
E
Silasi
D-A
DA
Azodi
M
M
Schwartz
P E
PE
Rutherford
T J
TJ
Pecorelli
S
S
Santin
A D
AD
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D002291:Carcinoma, Papillary / Q000097:blood* / Q000235:genetics / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein