Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour.
BACKGROUND
Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours.


OBJECTIVE
To investigate NOS expression in phyllodes tumours of varying degrees of malignancy.


METHODS
One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed.


RESULTS
Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p < 0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours.


CONCLUSIONS
Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.
Tse
G M K
GM
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong, China. garytse@cuhk.edu.hk
Wong
F C
FC
Tsang
A K H
AK
Lee
C S
CS
Lui
P C W
PC
Lo
A W I
AW
Law
B K B
BK
Scolyer
R A
RA
Karim
R Z
RZ
Putti
T C
TC
D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D018450:Disease Progression; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D003557:Phyllodes Tumor / Q000098:blood supply / Q000201:enzymology* / Q000556:secondary; D017154:Stromal Cells / Q000201:enzymology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III