ORIGINAL ARTICLE

Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour

G M K Tse¹, F C Wong¹, A K H Tsang¹, C S Lee⁵, P C W Lui³, A W I Lo¹, B K B Law², R A Scolyer⁵, R Z Karim⁵ and T C Putti⁴

¹ Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong, China
² Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong
³ Department of Pathology, United Christian Hospital, Kwan Tong, Kowloon, Hong Kong, China
⁴ Department of Pathology, National University Hospital, 5 Lower Kent Ridge Road, Singapore, 119074
⁵ Department of Pathology, University of Sydney, and Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, 2050 Australia

Correspondence to:
Correspondence to:
Dr G M Tse
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Ngan Shing Street, Shatin, NT, Hong Kong, China; garytse{at}cuhk.edu.hk

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.

Aims: 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.

Abbreviations: e/i-NOS, endothelial/inducible nitric oxide synthase; NO, nitric oxide; VEGF, vascular endothelial growth factor

Keywords: phyllodes; endothelial nitric oxide synthase; inducible nitric oxide synthase

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