Significance of inducible nitric oxide synthase expression in benign and malignant breast epithelium: an immunohistochemical study of 151 cases

Abstract

The role of calcium independent inducible nitric oxide synthase (iNOS) in breast carcinoma is controversial, and the implications of iNOS expression on prognosis are not known. In this study, we aimed to investigate the significance of immunohistochemical iNOS expression in 100 invasive ductal carcinomas. In addition, 11 normal breast tissues, 20 cases of usual ductal hyperplasias (UDHs) and 20 fibroadenomas were included. We found that 78% of malignant and 75% of benign cases showed iNOS immunoreactivity. However, the intensity and the quantity of iNOS expression were significantly higher in the cancer group when compared with benign breasts (P<0.001), suggesting a role of iNOS in breast carcinogenesis. We were unable to show a correlation between iNOS expression and tumor grade, axillary lymph node status, and estrogen receptor expression. In 50 axilla negative cases having 5--12 years follow-up, disease free survival (DFS) rate was significantly lower in cases showing strong iNOS expression (P=0.05). As strong iNOS expression was correlated with short DFS, we concluded that further studies would be necessary to elucidate if iNOS expression might be a useful prognostic marker in breast carcinoma, especially in the axilla negative group.

Increased NOS2 predicts poor survival in estrogen receptor–negative breast cancer patients

“…This analysis showed that high NOS2 is the single most significant predictor among them and predicts poor outcome of ER-negative breast cancer patients largely independent of these 3 factors (Supplemental Figure 7). Two other studies of breast cancer analyzed NOS2 expression in tumors and examined the relationship between NOS2 and patient outcome (41,42). In agreement with our findings and the study by Vakkala et al (13), NOS2 was found to be commonly expressed by the cancer cells themselves.…”

“…Previous reports indicated that elevated NOS2 expression may be linked to a high grade and poor prognosis in breast cancer (12,41,42), and also to poor outcome in other human epithelial cancers. In addition, mammary tumor latency is increased in NOS2-knockout mice (43).…”

Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study

“…As mentioned above, it seems that NO is mostly produced in cancer cells by iNOS. Most investigators found an adverse prognostic significance for iNOS expression (28)(29)(30) and nitrotyrosine tumor staining (which reflects intracellular NO levels) (21), whereas there is no direct evidence from the literature for the prognostic significance of plasma/serum NO levels (31,32). In the present study, high plasma NO levels predicted poor survival only in univariate analysis, apparently because of their direct correlation with the number of involved organs.…”

Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines

“…However, a dichotomy exists between enhanced radiosensitization and conditions where elevated levels of NO and up-regulated NOS are contributors to tumor progression. The relationship between NOS expression and tumor growth is evident in the literature from studies with a variety of cancer types including: (1) human oral squamous cell carcinoma [10,40], (2) gastric carcinoma [41], (3) lymph node metastases, and most significantly for this current work, (4) breast cancer, to a point that it is a universal property for human solid tumors [7,[15][16][17][42][43][44][45].…”