Matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, parathyroid hormone related protein and tissue expression of CD44v6 in metastatic breast cancer

Matrix metalloproteinases [MMPs] and their inhibitors [TIMPs] modulate ECM composition and may affect breast cancer invasion and metastases. Bone metastases are a frequent complication of advanced breast cancer. This work investigated the relationship between plasma levels of MMP-9, TIMP1, PTHrP, tissue expression of CD44v6 and the development of nodal and bone metastases in 40 female patients with different stages of breast cancer. The control group comprised 10 females with benign breast lesions. All studied parameters were significantly higher in patients than in controls. Patients with lymph node involvement has significantly higher plasma MMP-9, MMP9/TIMP-1 ratio and CD44c6 expression than those without nodal affection, [p= 0.018, 0.006 and 0.02 respectively]. Higher MMP-9 MMP9/TIMP-1 ratio and PTHrP were found in patients with than those without bone metastases [p = 0.013, 0.01 and 0.0002 respectively]. CD44v6 expression was associated with increased MMP-9 and TIMP-1 levels as well as higher tumour grade. Post-operative MMP-9 was significantly lower than pre-operatively. Our data indicate that increased plasma MMP-9 and MMP-9 / TIMP-1 imbalance may be useful markers for development of nodal and bone meatstases in breast cancer patients and in predicting post-operative recurrence. While CD44v6 is involved in nodal metastases, PTHrP seems to be an important determinant of development of bone secondaries

Role of sentinel lymph node biopsy in the management of patients with breast cancer

The status of the axillary lymph node basin remains the most powerful predictor of survival in patients with invasive breast cancer. Lymphatic mapping concept entails that lymphatic drainage from primary tumors can be mapped to the regional lymph nodes. The first node[s] of these nodes, i.e., the SLN, can then be identified and removed. This node is supposed to be the initial site of metastatic disease, and the histologic characteristics of the SLN reflect the state of the remaining nodes in the lymphatic basin. The preliminary reports of lymphatic mapping and SLN biopsy in breast cancer have shown this technique to be an accurate axillary staging procedure. It is a less invasive procedure and therefore is associated with a lower rate of complications, such as postoperative lymphoedema, seroma formation, and neuropathy of the arm, than complete ALND. It also allows more detailed examination of the lymph node at greatest risk for metastatic disease. This can be performed by serially sectioning the SLN and applying immunohistochemical [IHC] stains to the specimens, thereby enhancing the detection of nodal metastatic disease. The present study aimed at: comparing peritumoural injection with subareolar injection of dye in identifying SLN/s. Also, identifying the presence of micrometastases in the SLN/s by serial sectioning of the SLN/s and H and E staining or cytokeratin stains. The study was performed on 94 patients with stages I and II breast cancer equally divided into two groups according to method of injection of dye each of 47 patients. SLN were successfully mapped in 84 patients. Fifty three of them harbored metastases. In 45 patients metastases was discovered by ordinary H and E technique. Micrometastases were discovered in eight more patients [5 by serial sectioning of lymph nodes and H and E examination and 3 by immunohistochemical staining. The use of SLN alone would have led to understaging in two patients. It can be concluded that SLN biopsy is an accurate and useful technique. A thorough knowledge of its different methods, its indications as well as limitations maximize the value of this techniques to the oncologic surgeon. The use of modern staining techniques helps also in detecting minimal disease and allows for appropriate treatment decisions