Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer

We aimed to evaluate the expression of sarcosine metabolism-related proteins according to site of metastatic breast cancer, and the clinical implications. Immunohistochemical staining for glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX) was performed on tissue microarrays from 162 metastatic breast cancer (bone metastases = 47, brain metastases = 39, liver metastases = 24, and lung metastases = 52). Sarcosine metabolism-related proteins showed variable expression with regard to metastatic sites. GNMT was expressed in brain and lung metastases, but not in bone and liver metastases (P = 0.016). In view of the sarcosine metabolic phenotype, high sarcosine and intermediate type were only found in the brain and lung metastases, and low sarcosine type was observed more frequently in bone and lung metastases (P = 0.047). By univariate analysis, PIPOX positivity was correlated with shorter overall survival (OS) (P = 0.031). In lung metastases, PIPOX positivity (P = 0.019) and stromal PIPOX positivity (P = 0.001) were associated with shorter OS. In conclusion, in metastatic breast cancer, sarcosine metabolism-related proteins are differently expressed according to the metastatic site. Expression of GNMT and high sarcosine type are predominantly observed in brain and lung metastases.     

Effect of Gleason scores of lymph node metastases on prognosis of patients with prostate cancer

The long-term mortality risk from prostate cancer increases in lymph node (LN) positive patients. This study was done to assess the effect of lymph node Gleason score (LNGS) on prognosis in patients with LN-positive prostate cancer. Among the 1,415 patients who received pelvic lymph node dissection (PLND), 117 (8.4%) patients had a positive LN. The PGS of the prostate specimens and the LNGS of the positive LNs were assessed by uropathologists. The median age of patients at surgery was 67 years (interquartile range [IQR], 62-71 years) and the median follow-up duration was 44.3 months (IQR, 27.0-78.5 months). Pathologic Gleason scores (PGS) of 6-9 included one (0.9%), 53 (49.5%), 22 (20.6%), and 31 (29.0%) patients. The median total number of retrieved LNs was 9.0 (IQR, 5.3-12.8). The median number of positive LNs was one (IQR, 1-2). Cancer architecture with a Gleason pattern and score were observed in LNs as in ordinary prostate specimens. LNGS 6-9 included nine (8.1%), 57 (51.4%), 31 (27.9%), and 14 (12.6%) patients. The speaman’s analysis showed the meaningful correlation between PGS and LNGS (P = 0.249, P = 0.011). The univariate analysis showed that the number of positive LNs and LNGS were significantly associated with prostate cancer-specific survival (P = 0.028; P = 0.005). The same architecture that is seen in the prostate was seen in positive LNs, and LNGS may be a significant prognostic factor in patients with LN-positive prostate cancer.     

Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal

Background/Aims

A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal.

Methods

The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis.

Results

Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD.

Conclusions

Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.     

Advancing Biomarker Development Through Convergent Engagement: Summary Report of the 2nd International Danube Symposium on Biomarker Development,Molecular Imaging and Applied Diagnostics; March 14–16, 2018; Vienna,Austria

Molecular Imaging and Biology - Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During...     

Expression of p16INK4a,p15INK4b,p21WAF1/Clip1 cell cycle inhibitors on blastic cells in patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL)

Cyclin-dependent kinases (cdk) play the important role in neoplastic transformation. Their activity depends on interaction with proteins called inhibitors. There are two groups of inhibitors: INK4 (p16INK4a, p15INK4b, p18INK4c, p19INK4d) and proteins p21WAF1/Clip1, p27Kip1, p57Kip2. Alteration of inhibitors expression was assessed in acute lymphoblastic leukemia (ALL) and in acute myeloblastic leukemia (AML), but the results are not clear. The aim of our study was to estimate p16INK4a, p15INK-4b, p21WAF1/Clip1 expression in blast cells in patients with AML and ALL by cytochemistry method and to compare with the result of treatment. Forty-two patients were included in the study, 23 with AML and 19 with ALL. Expression of inhibitors was considered as positive when detected in > 5% of blast cells. Complete remission (CR) rate in patients with positive expression p16INK4a and p15INK4b was statistically significantly higher than in patients with negative expression: for p16INK4a chi 2 = 7.78, p < 0.01, for p15INK4b, chi 2 with Yates' modification = 3.94, p < 0.05. There was no difference in CR rate in patients with positive and negative p21WAF1/Clip1 expression. Moreover the patients with simultaneous expression of three inhibitors reached CR more often than the others: chi 2 = 7.43, p = 0.01 for AML and chi 2 = 6.74, p < 0.01 for ALL. Our study indicates that estimation of p16INK4a, p15INK4b, p21WAF1/Clip1 expression in blast cells can be used as prognostic factor in acute leukemia.     

Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with the APOE p.Leu167del Mutation

Apolipoprotein (apo) E mutants are associated with type III hyperlipoproteinemia characterized by high cholesterol and triglycerides levels. Autosomal dominant hypercholesterolemia (ADH), due to the mutations in the LDLR, APOB, or PCSK9 genes, is characterized by an isolated elevation of cholesterol due to the high levels of low‐density lipoproteins (LDLs). We now report an exceptionally large family including 14 members with ADH. Through genome‐wide mapping, analysis of regional/functional candidate genes, and whole exome sequencing, we identified a mutation in the APOE gene, c.500_502delTCC/p.Leu167del, previously reported associated with sea‐blue histiocytosis and familial combined hyperlipidemia. We confirmed the involvement of the APOE p.Leu167del in ADH, with (1) a predicted destabilization of an alpha‐helix in the binding domain, (2) a decreased apo E level in LDLs, and (3) a decreased catabolism of LDLs. Our results show that mutations in the APOE gene can be associated with bona fide ADH.