Steroidogenesis in ovarian-like mesenchymal stroma of hepatic and pancreatic mucinous cystic neoplasms.

STEROIDOGENESIS IN HEPATIC MUCINOUS CYSTIC NEOPLASM: Aim Mucinous cystic neoplasms (MCNs) occur in the ovary, pancreas, and retroperitoneum but very rarely in the liver. Mucinous cystic neoplasms are known to harbor ovarian-like mesenchymal stroma (OLS) expressing progesterone and estrogen receptors. In this study we evaluated steroidogenesis in OLS of 25 hepatic MCNs and 24 pancreatic MCNs. Methods Both steroid receptors and steroidogenic factors were immunohistochemically evaluated using H-scores and results were compared with those in 15 ovarian MCNs and 10 normal ovaries. Results Androgen receptor (AR) H-scores in OLS were significantly higher in hepatic, pancreatic, and ovarian MCN than those in normal ovaries. H-scores of cytochrome P450 17α-hydroxylase/c17-20 lyase (P450c17) and 5α-reductase-1 (5αRED-1) in the stroma were significantly higher in OLS of hepatic and pancreatic MCN than in the stroma of ovarian MCN and normal ovary. In tumor epithelium, AR H-scores were significantly higher in hepatic and pancreatic MCN than in ovarian MCN. In both hepatic and pancreatic MCN, a significant positive correlation was detected between AR H-score in the epithelium and P450c17 H-score in OLS (hepatic MCN: Pearson's r = 0.446, P = 0.025; pancreatic MCN: r = 0.432, P = 0.035). In pancreatic MCN, a significantly positive correlation was detected between AR H-score in the tumor epithelium and 5αRED-1 H-score in OLS (Pearson's r = 0.458, P = 0.024). Conclusions These results indicated that locally produced androgens in OLS could be pivotal for tumorigenesis of both hepatic and pancreatic MCN and influence epithelial cells, possibly in a paracrine fashion, which could represent biological significance of OLS in these neoplasms.

Tyrosine kinase inhibitor-induced vasculopathy in clear cell renal cell carcinoma: an unrecognized antitumour mechanism.

AIMS: To evaluate the pathological features of clear cell renal cell carcinoma (CCRCC) treated with tyrosine kinase inhibitors (TKIs), and to elucidate the mechanism of action of TKIs. METHODS AND RESULTS: Twenty cases of CCRCC treated with TKIs (sorafenib or sunitinib) were retrospectively analysed: 16 were patients who had undergone radical nephrectomy after neoadjuvant TKI therapy, and four were autopsy cases of patients who received TKI treatment. All tumours had two distinct regions: one characterized by necrosis and/or degeneration, indicating antitumour activity; and the other characterized by no or few pathological changes, indicating the absence of antitumour activity. Vasculopathy of tumour vessels was observed in or adjacent to the necrotic or degenerative areas; a decreased density of endothelial cells was noted in the tumour vessels. Few or no changes of vasculopathy were observed in tumour vessels in the other CCRCC areas, indicating the absence or low levels of antitumour activity. CONCLUSIONS: This is the first pathological report of vasculopathy in TKI-treated CCRCC cases. Our data suggest that TKIs initially induce vasculopathy in tumour vessels, and consequently cause reduction or diminution of blood supply to the CCRCCs, resulting in antitumour activity characterized by necrosis and hyalinization.

Staphylococcal cassette chromosome mec(SCC mec) analysis of MRSA.

Methicillin-susceptible Staphylococcus aureus changes to methicillin-resistant S. aureus (MRSA) on acquisition of the staphylococcal cassette chromosome mec (SCCmec). At least five types of SCCmec elements have been reported. All the SCCmec elements share four common characteristics: (1) the elements carry the mec gene complex (mec); (2) they carry the ccr gene complex (ccr); (3) the elements are flanked by characteristic nucleotide sequences, both inverted repeats and direct repeats, at both ends; and (4) the SCCmec elements are integrated at the 3' -end of orfX. In the two essential components, mec and ccr, four classes of mec and five types of ccr have been identified. SCCmec elements can be defined by the different combinations of mec and ccr types. Regions other than mec and ccr within the element are designated junkyard regions (J regions). Even in the same SCCmec type, these regions are not always identical and have therefore been regarded as good targets for subtyping SCCmec elements in epidemiological studies. Nucleotide differences in the J1 region and/or the presence of inserted plasmids and transposons, most of which encode resistant determinants integrated in the J2 and J3 regions, can be used to further classify SCCmec types. In this chapter, we describe polymerase chain reaction methods to type SCCmec elements by first identifying the mec and ccr type, and subsequently identifying genes in the J regions.

[Community-associated methicillin-resistant Staphylococcus aureus: current status and molecular epidemiological perspective].

MRSA has been a major causative agent of nosocomial infection. However, recently MRSA has become increasingly isolated from community-associated infections. We summarized here up to date information about community-associated MRSA (C-MRSA) infections and characteristics of C-MRSA strains based on molecular analysis. By using the SCCmec typing, strong evidence was provided for the independent derivation of healthcare-associated MRSA and C-MRSA clones.