Expression of autophagy-related proteins in phyllodes tumor

Phyllodes tumors (PTs) are classified as fibroepithelial tumors and their histologic grade is determined primarily by the features of the stromal component. In this study, we examined the expression profiles of autophagy-related proteins in the stromal component of PTs and analyzed their clinical implications. We selected 204 human PT samples which were excised and diagnosed at Severance Hospital from 2000 to 2008 and created tissue microarray (TMA) blocks. Immunohistochemical assays for autophagy-related proteins (beclin-1, LC3A, LC3B, and p62) were then performed on these samples. The surgical specimens from higher grade PTs less frequently displayed cytoplasmic expression of beclin-1, LC3A, LC3B, and p62 in the stromal component (p<0.001). In univariate analysis, the following profiles were associated with shorter disease-free survival and overall survival: nuclear beclin-1 positivity in the stromal component (p=0.013 and p=0.044, respectively), LC3A positivity in the stromal component (p<0.001 and p<0.001, respectively), and p62 positivity in the stromal component (p=0.012 and p=0.004, respectively). In conclusion, we determined that increased activity of autophagy-related proteins correlated with a higher histologic grade and poorer prognosis in PTs. These results lead us to conclude that the autophagy activity of the stromal cells plays a key role in the progression of PTs.     

Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis

Background/Aims

We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis.

Methods

Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated.

Results

The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4.

Conclusions

The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.     

Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus

Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are nonspecific, and include abdominal discomfort, mild hepatomegaly, and transaminase elevation. In this report we describe three cases of patients presenting serum transaminase elevation and hepatomegaly with a history of poorly controlled type I DM. All of the cases showed sudden elevation of transaminase to more than 30 times the upper normal range (like in acute hepatitis) followed by sustained fluctuation (like in relapsing hepatitis). However, the patients did not show any symptom or sign of acute hepatitis. We therefore performed a liver biopsy to confirm the cause of liver enzyme elevation, which revealed GH. Clinicians should be aware of GH so as to prevent diagnostic delay and misdiagnosis, and have sufficient insight into GH; this will be aided by the present report of three cases along with a literature review.     

Estimating the origin and evolution characteristics for Korean HIV type 1 subtype B using Bayesian phylogenetic analysis

The majority of Korean human immunodeficiency virus type 1 (HIV-1) isolates are composed of the Korean clade B strain that is distinct from the subtype B prevalent in North America and Europe. However, it is still not clear how HIV-1 was introduced, transmitted, and evolved within the Korean population. To identify the evolutionary characteristics of Korean HIV-1, we estimate the molecular epidemic history of HIV-1 subtype B gp120 env in Korea in comparison with sequences isolated from other geographic locations. A Bayesian Markov chain Monte Carlo (MCMC) statistical inference was used to estimate the time of divergence of subtype B. The estimated time of divergence of subtype B and the distinct monophyletic Korean B cluster was estimated to be in the early and mid-1960s, respectively. Substitution rates were estimated at 7.3×10(-3) and 8.0×10(-3) substitutions per site per year for HIV-1 subtype B and Korean clade B, respectively. The demographic dynamics of two Korean data sets showed that the effective number of infections in Korea increased rapidly until the early 1980s, and then the rate only slowly increased until the mid-1990s when the population growth approached a steady-state. These results suggest that the growth rate of prevalent HIV-1 strains in Korea was lower than in other countries, suggesting that the evolution of HIV-1 Korean clade B was relatively slow. Furthermore, the limited transmission of HIV-1 within the Korean population likely led to the independent evolution of this virus to form the HIV-1 Korean clade B.