AMP-activated protein kinase (AMPK) is activated by the depletion in cellular energy levels and allows adaptive changes in cell metabolism and cell survival. Recently, our group described that AMPK plays an important role in the regulation of iodide and glucose uptake in thyroid cells. However, AMPK signaling pathway in human thyroid carcinomas has not been investigated so far. Objective: To evaluate the expression and activity of AMPK in papillary thyroid carcinomas. Methods: We examined total and phosphorylated AMPK (tAMPK and pAMPK) and phosphorylated acetyl-CoA-carboxylase (pACC) expressions through imunohistochemistry, using a tissue microarray block composed of 73 papillary thyroid carcinomas (PAP CA) or microcarcinomas (PAP MCA) and six adenoma (AD) samples from patients followed at the Federal University Hospital. The expression levels were compared with the non-neoplastic tissues from the same patient. Two different pathologists analyzed the samples and attributed scores of staining intensity and the proportion of stained cells. A total index was obtained by multiplying the values of intensity and the proportion of stained cells (INTxPROP). Results: tAMPK, pAMPK, and pACC showed a predominant cytoplasmic staining in papillary carcinomas, adenomas, and non-neoplastic thyroid tissues. However, the intensity and the proportion of stained cells were higher in carcinomas, so that a significant increase was found in the INTxPROP score both in PAP CA and PAP MCA, when compared with their respective controls. Conclusion: Our results show unequivocally that AMPK pathway is highly activated in papillary thyroid carcinomas; however, more studies are necessary to understand the pathophysiological significance of AMPK activation in thyroid carcinogenesis.

BackgroundAngiogenesis is a proliferative process resulting in the development of new blood vessels from existing endothelial cells and is considered crucial for tumor growth and metastasis. Tumor angiogenesis can be quantified by microvascular density (MVD), which is evaluated in highly vascularized tumor areas (hot spots) by immunohistochemical assays using CD34 and CD31 pan-endothelial antibodies. More recently, CD105 has been successfully used for some tumor types because it could discriminate neovascularization. The expression of CD34 and CD105 in hepatocellular carcinomas (HCC) and hepatic precancerous lesions has been reported—although the results for CD105 are controversial—but to the best our knowledge, CD105 has not been previously investigated in dysplastic nodules (DN). We investigated and compared MVD-CD34 and MVD-CD105 immunoexpression in tissues containing different stages of hepatocarcinogenesis, including DN.MethodsA total of 31 regenerative nodules (RN), 26 DN and 25 small HCC from explants were used for immunohistochemical tests with CD34 and CD105 antibodies. Antibody expression was quantified by computerized image analysis measurement of MVD, areas containing highly positive endothelial cells within the nodules.ResultsThe median MVD for CD34 was higher in HCC than in DN and RN (p < 0.01), and was higher in DN compared with RN (p = 0.033). In contrast, MVD with CD105 was higher in RN, and the difference was significant in RN and DN compared with HCC (p = 0.019 and p = 0.012, respectively). When MVD with CD34 and CD105 were compared within a single group, there was a significant predominance of CD105 in RN and DN (p < 0.01). In addition, MVD-C34 in HCC predominated compared with MVD-CD105, but the difference was not statistically significant (p = 0.128).ConclusionsThis study identified a close relationship between CD105 and liver cirrhosis, and that CD34 antibody is a good endothelial marker for hepatic carcinogenesis. There was no difference between the use of CD105 and CD34 antibodies in preneoplastic lesions.

Inflammatory myofibroblastic tumor (IMT) occurs infrequently in the liver. It is controversial whether it represents a low grade mesenchymal neoplasm or a reactive inflammatory lesion. Local recurrence and metastasis are rare and some tumors are associated with infectious agents. We report on a case of a large and partially resected IMT with local recurrence and diaphragm and kidney infiltration detected on routine surveillance two years later. Histologically, the tumor showed spindle cells without atypia, mitosis or necrotic areas in a myxoid and collagenized background with inflammatory cells. In the liver portal tracts, granulomatous lesions with viable eggs of Schistosoma mansoni were identified. Immunohistochemistry demonstrated spindle cells which were smooth-muscle actin and vimentin positive. In conclusion, this case points out that these histological patterns do not predict the aggressive biological behavior of the lesion. A reason for the recurrence and the infiltration may be incomplete tumor resection. Further investigation is necessary in order to better clarify an infectious cause in some IMTs.

No abstract