Clinical relevance of lymph node ratio in breast cancer patients with one to three positive lymph nodes.

BACKGROUND: To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT). METHODS: Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR). RESULTS: Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17-0.89; P=0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT. CONCLUSION: This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.

Reduced expression of tissue inhibitor of metalloproteinase in nodal metastasis of stomach cancer.

The matrix metalloproteinases (MMPs) have been associated with tumor cell invasion and metastasis of human cancers by mediating the degradation of extracellular matrix components. Therefore, these enzymes and their inhibitor (TIMP-2) constitute promising targets in the development of anticancer therapies. In order to investigate the correlation between expressions of TIMP-2, MMPs and clinical outcome, immunohistochemical staining of MMP-2, MMP-9, and TIMP-2 were performed on paraffin-embedded tissue sections of 15 early gastric cancers (EGC) and 15 advanced gastric carcinomas (AGC) without nodal metastasis and 15 AGC with nodal metastasis (AGCn+). MMP-2 and MMP-9 were expressed in neoplastic cell plasma membrane in 83.3% and 88% of cases of AGC, respectively with inter-tumoral variability of staining intensity. MMP-2 and MMP-9 staining were not correlated with presence of nodal metastasis or degree of invasion depth at the time of diagnosis (p>0.05). The immunoreactivity of TIMP-2 was detected in the peri-tumoral stroma. Residual benign stomach tissue showed no or weak immunoreactivity for TIMP-2 staining. Among AGC, neoplasms with diffuse and strong TIMP-2 staining have less frequent metastasis (28.6%) than cases with focal and weak (68.8%) (p<0.05). Early gastric cancer revealed diffuse and strong TIMP-2 expressions. We conclude that clinical outcome such as depth of invasion or metastasis is more closely related to the expression of TIMP-2 than the corresponding MMPs.