Purpose: Cell signaling pathways include a complex myriad of interconnected factors from the membrane to the nucleus, such as erbB family receptors and the phosphoinositide-3-kinase/Akt/ mTOR and Ras-Raf-ERK cascades, which drive proliferative signals, promote survival, and regulate protein synthesis. Experimental Design: To find pivotal factors in these pathways, which provide prognostic information in malignancies, we studied 103 human breast tumors with an immunohistochemical profile, including total and phosphorylated (p) proteins: human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, Akt, 4E-binding protein 1 (4EBP1), eukaryotic initiation factor 4E, phosphorylated ribosomal protein S6 kinase 1, phosphorylated ribosomal protein S6, and Ki67.Western blot and reverse lysate protein arrays were also done in a subset of tumors. Results: Significantly, activation of the phosphoinositide-3-kinase/Akt/mTOR cascade was detected in a high proportion of tumors (41.9%). Tumors with HER2 overexpression showed higher p-Akt as compared with negative tumors (P < 0.001). Levels of p-Akt correlated with the downstream molecules, p-4EBP1 (P = 0.001) and p-p70S6K (P = 0.05). Although 81.5% of tumors expressed p-4EBP1, in 16.3% of these tumors, concomitant activation of the upstream factors was not detected. Interestingly, p-4EBP1 was mainly expressed in poorly differentiated tumors (P < 0.001) and correlated with tumor size (P < 0.001), presence of lymph node metastasis (P = 0.002), and locoregional recurrences (P = 0.002). Coexpression of p-4EBP1 and p-eIF4G correlated with a high tumor proliferation rate (P = 0.012). Conclusion: In this study, p-4EBP1was the main factor in signaling pathways that associate with prognosis and grade of malignancy in breast tumors. Moreover, p-4EBP1 was detected in both HER2-positive and HER2-negative tumors. This factor seems to be a channeling point at which different upstream oncogenic alterations converge and transmit their proliferative signal, modulating protein translation.Human tumors are characterized by their great heterogeneity and histopathologic variability. Currently, >250 malignant tumors and thousands of subtypes and histologic variants have been described. Nevertheless, the classic pathologic criteria, such as tumor size, grade of malignancy, and metastatic dissemination, are generally the most relevant prognostic factors in cancer. In addition to the variability of histopathologic subtypes, molecular study of tumors is even more complex. In all malignant tumors, at least six genetic alterations should affect the main mechanisms of cellular transformation, including growth factor and cell signaling pathways, the cell cycle, apoptosis, and mechanisms implicated in cellular invasiveness, and angiogenesis (1 -3). Overall, >350 genes associated with cancer have been identified, representing >1% of the human genome (4).Studies using cDNA expression arrays have detected hundreds of genetic alterations w...

After NAC, FS is an effective method for detecting macrometastasis in the SLN. As in the adjuvant setting, the sensitivity of FS is lower for SLN micro and sub-micrometastasis. Intraoperative FS of the SLN after NAC is indicated to avoid a second surgery because 60% of patients with a positive SLN will have additional positive axillary nodes.

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Inorganic element content in pleura and lung was studied by energy-dispersive X-ray analysis (EDXA) and scanning electron microscopy (SEM) in reference, exposed non-pneumoconiotic, and silicotic populations. Samples of parietal pleura, visceral pleura, and lung in 11 subjects with no measurable exposure to inorganic dust and of visceral pleura and lung samples of 10 exposed non-pneumoconiotic individuals and eight silicotic patients were examined. Constant depositions of silicon and calcium were detected in visceral pleura, parietal pleura, and lung of the reference group and in visceral pleura and lung of the exposed non-pneumoconiotic and silicotic groups. Other elements, such as aluminum and iron, were also detected in the exposed non-pneumoconiotic and silicotic patients and, less frequently, in the reference group. There was no difference in silicon content between parietal and visceral pleura in the reference group. Silicon content in silicotic patients was higher and more irregularly distributed in the pleura (p = 0.005 and p < 0.01, respectively) and in the lung (p = 0.005 and p < 0.01, respectively) than in the reference group. Comparison of the silicon content in pleura between silicotic and exposed non-pneumoconiotic subjects showed a nonsignificant probability of difference (p = 0.052), whereas there were no differences with respect to the silicon content in lung. There were no differences in the pleural and lung silicon content between the exposed non-pneumoconiotic and reference groups.(ABSTRACT TRUNCATED AT 250 WORDS)

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