Predicting sentinel lymph node metastases in infiltrating breast carcinoma with vascular invasion.

Sentinel lymph node and clinically negative axillary node status was compared with well-known clinicopathological characteristics such as tumor size, histologic and nuclear grade, lymphovascular invasion, steroid receptor, and HER-2 status in patients with breast cancer (pT1 and pT2). Positive sentinel lymph nodes were found in 29 of 100 patients: 19 with metastases detected by hematoxylin and eosin staining and 10 with micrometastases confirmed by immunohistochemistry with cytokeratin. Positive sentinel lymph nodes were present in larger carcinomas (P < 0.03), more frequently in tumors with negative PR status (P < 0.037) and evident lymphovascular invasion (P < 0.002). Lymphovascular invasion was also associated with breast cancer of higher histologic (P = 0.011) and nuclear grade (P = 0.039). Tumor size and the presence of lymphovascular invasion were found to be significant predictors of pathologically positive sentinel lymph node in T1 and T2.

Antihypertensive treatment and renal damage: amlodipine exerts protective effect through the polyol pathway.

Besides generating renal damage, hypertension plays an important role in the progression of diabetic nephropathy. The fructose-fed rat is a well-established model both of high blood pressure and renal impairment, which is similar to diabetic nephropathy. To clarify the relationship between hypertension, glucose metabolism, and kidney remodeling, we investigated the renal level of Glut 1 and Glut 5, their relation to fibrosis and the effects of an antihypertensive drug on renal damage. Twenty-four male WK rats were divided into three groups: 8 animals received a fructose-enriched diet, 8 a control diet, and 8 animals a high-fructose diet plus amlodipine (5 mg/Kg). After six weeks of treatment, we observed a significant increase in Glut 5, fibronectin, and sorbitol in fructose-fed rats compared with control and amlodipine-treated animals; there was a positive correlation between Glut 5 and fibronectin levels (r = 0.63). Glut 1 levels were similar in all three groups, whereas collagen IV was higher in fructose-fed rats; amlodipine prevented the increase of collagen IV and sorbitol. Collagen I was statistically higher in the fructose group than in the other two groups. Therefore, prolonged fructose feeding results in renal fibrosis via polyol pathway overactivity that can be prevented by means of an antihypertensive drug.

Flow cytometry expression of p53 and PCNA in oral/oropharynx carcinomas and their lymph node metastases.

The aim of this work was to characterize p53 and PCNA expression in primary tumours and lymph node metastases of oral/oropharynx carcinomas by flow cytometry and to evaluate the possibility of a relationship between these parameters in primary tumours and locoregional metastasis, clinical-histopathological parameters and survival time. A group of 28 patients was retrospectively selected: 13 with metastasis and 15 without metastasis. The following clinical and histopathological parameters were considered: degree of keratinization, Broders' grading of histological differentiation, invasive cell grading, thickness and tumour size. The nuclei of appropriately prepared cells were stained using anti-p53 and anti-PCNA FITC conjugated monoclonal antibodies. Analyses were performed by a Coulter Epics Elite flow cytometer. The following results were obtained: a close relationship between p53 and PCNA in primary tumours but no correlation between them and clinical-histopathological parameters; no correlation between p53 and PCNA expression in primary tumours and in lymph node metastasis; no correlation between p53 and PCNA values in primary tumours and survival. In conclusion, the difference in expression of these biological parameters in primary tumours and in lymph node metastases supports the theory that tumour cells in lymph nodes can display an independent behaviour. Since these biological parameters fail to correlate either with clinical-histopathological parameters or survival, their prognostic role is questionable.

Correlation between vascular endothelial growth factor, angiogenesis, and tumor-associated macrophages in invasive ductal breast carcinoma.

Angiogenic and anti-angiogenic factors, secreted by tumor, inflammatory, and stromal cells play an important role in regulation of neovascularization. Among the most important of these is vascular endothelial growth factor (VEGF), a specific mitogen for endothelium, which increases vascular permeability and induces proteolytic enzymes necessary for vascular remodeling. Tumor-associated macrophages (TAMs) can express complex functions related to tumor biology, including growth, proliferative rate, stroma formation and dissolution, and neovascularization. The aim of this study was to define, using immunohistochemical analysis, the microvessel density (MVD), VEGF expression, and TAMs level in 97 human invasive ductal breast carcinomas not otherwise specified (NOS), investigate a possible relationship between them and then correlate their values with tumor grade, mitotic activity index (MAI), tumor size and lymph-node status. Statistical analysis showed a strong positive relationship between MVD and VEGF expression ( P<0.001). Furthermore, both MVD and VEGF expression were significantly correlated with tumor grade and lymph-node status, and TAMs infiltration with MAI. TAM level showed a significant positive connection with VEGF expression and MVD. These in situ observations suggest that VEGF stimulates angiogenesis in human invasive ductal breast carcinoma NOS and attracts macrophages to the tumor locus, which then may be involved in angiogenesis promotion. The expression of this angiogenic molecule, and MVD and TAM level, can provide additional prognostic significance and help in the identification of patients who need postoperative adjuvant therapy.

Do Ki67, S-phase, S + G2M and DNA ploidy, evaluated by flow cytometry, reveal locoregional metastasis in oral cavity and oropharynx carcinomas?

Tumour cell proliferation is an important biological prognostic parameter to be considered alongside clinical and histopathological parameters. It has been evaluated by immunohistochemistry using proliferative markers (PCNA, Ki67, etc.) and by flow cytometry considering DNA content, growth fraction (S + G2M) and S-phase fraction. Our aim was to evaluate by flow cytometry both Ki67 and S-phase fraction, S + G2M, DNA content in patients surgically treated for oral cavity and/or oropharynx carcinomas. The study, performed on archival material, analysed the significance and prognostic reliability of these biological parameters to reveal locoregional metastasis and evaluated their possible correlation with clinical and histopathological parameters. In conclusion, tumour cell proliferation seems not to be useful in revealing the presence of locoregional metastasis in oral cavity and oropharynx carcinomas. Thus, new approaches are required.