Clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large‐format histologic sections

Abstract

We investigated whether AMP‐activated protein kinase (AMPK), a multi‐functional regulator of energy homeostasis, participates in the regulation of erythropoietin (EPO)‐mediated activation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) and mice. In ECs, treatment with EPO increased the phosphorylation of AMPK, acetyl‐CoA carboxylase (ACC), and eNOS, as revealed by Western blot analysis. Inhibition of AMPK activation by compound C or dominant‐negative AMPK mutant abrogated the EPO‐induced increase in the phosphorylation of AMPK, ACC, and eNOS, as well as nitric oxide (NO) production. Additionally, suppression of AMPK activation abolished EPO‐induced EC proliferation, migration and tube formation. Immunoprecipitation analysis demonstrated that AMPK mediated the EPO‐induced increase in the phosphorylation of β common receptor (βCR) and the formation of a βCR–AMPK–eNOS complex. In mice, inhibition of AMPK activation by compound C markedly decreased EPO‐elicited angiogenesis in Matrigel plugs. Furthermore, the phosphorylation of AMPK and eNOS was significantly higher in aortas from EPO transgenic mice than wild‐type mice. Moreover, treatment with EPO neutralizing antibody greatly reduced the exercise training‐induced increase in phosphorylation of AMPK and eNOS in aortas of wild‐type mice. Taken together, EPO may trigger AMPK‐dependent signaling, which leads to enhanced phosphorylation of βCR and eNOS, increased βCR–AMPK–eNOS complex formation, NO production, and, ultimately, angiogenesis. J. Cell. Physiol. 227: 3053–3062, 2012. © 2011 Wiley Periodicals, Inc.

Application of a novel prognostic invasive lesion index in ductal carcinoma in situ with minimal invasion of the breast

“…Therefore, it could be an additional predictor for LNM in this tumor category. This conclusion is consistent with previous findings 15, 16, 17. In a study of 301 consecutive cases of 1–14 mm invasive breast carcinomas, Tibor and his colleagues found that mutifocality of the invasive component was associated with a substantially elevated risk of vascular invasion and LNM 18.…”

The role of radiological–pathological correlation in diagnosing early breast cancer: the pathologist’s perspective

“…According to the results of our previous studies [9][10][11], approximately one-third of all breast carcinomas are unifocal, the rest are multifocal or diffuse due to distribution of the in situ or the invasive tumor foci, or both. In addition, in about one-half of cases, the malignant lesions occupy a space larger than or equal to 4 cm in the largest dimension (extensive tumors).…”

“…These lesions are often nonpalpable, of small size, and hardly visible with the naked eye. Nevertheless, despite their small size, early breast carcinomas are often multifocal and extensive [7][8][9][10][11], and the multiple foci within the same tumor may occupy a several centimeter large tissue volume. This indicates the need for using special nonfragmenting histology technique in these cases and also underlines the paramount importance of a detailed radiological-pathological correlation in diagnosing early breast cancer.…”

Review on Practical Approach in Multiple Breast Carcinomas: Does Each Focus Matter?

“…Most of these authors only took into account grossly visible foci and ignored microscopic foci. Other authors (12,13,14,29) used both terms together, without making a difference between MF and MC by avoiding "quantitative" delimitations. They considered breast carcinomas to be multiple when multiple invasive foci separated by benign breast tissue are seen, regardless of the distance between foci; topographic criteria and distance between tumor foci are considered by these authors to be parameters of debatable biological significance (5).…”