Apmis

doi: 10.1111/apm.12872pmid: N/A

Blanca, Ana; Sanchez‐Gonzalez, Alvaro; Requena, Maria J.; Carrasco‐Valiente, Julia; Gomez‐Gomez, Enrique; Cheng, Liang; Cimadamore, Alessia; Montironi, Rodolfo; Lopez‐Beltran, Antonio

doi: 10.1111/apm.12973pmid: 31231851

microRNA alterations are involved in bladder cancer tumorigenesis. The aim of the current study was to evaluate the potential role of miR‐100 and miR‐138 as prognostic biomarkers in Ta/T1 non‐muscle‐invasive bladder cancer (NMIBC). We assessed a quantitative RT‐PCR analysis of miR‐100 and miR‐138 in 50 bladder tumor samples (stage Ta/T1) and four healthy adjacent tissues. Western blot analysis was used to measure protein expression of FGFR3 and cyclin D3 in order to know whether these targets can be regulated by miR‐100 and miR‐138, respectively. The statistical analysis included non‐parametric tests (Mann–Whitney U and Kruskal–Wallis) and univariate survival analysis by Kaplan–Meier method and the log‐rank test. Low expression of miR‐138 characterized recurrent tumors (p = 0.043), and higher expression levels were associated with longer recurrence‐free survival (p = 0.012). However, low miR‐100 expression correlated with longer progression‐free survival (marginal significance; p = 0.053) and cancer‐specific overall survival (p = 0.006). Additionally, higher levels of miR‐100 were associated with negative FGFR3 protein expression (p = 0.032) and higher levels of miR‐138 were associated with positive cyclin D3 protein expression (p = 0.037). Our results support miR‐138 and miR‐100 as prognostic biomarkers in patients with NMIBC.

Lindh, Claes; Kis, Lorand; Delahunt, Brett; Samaratunga, Hemamali; Yaxley, John; Wiklund, Nils Peter; Clements, Mark; Egevad, Lars

doi: 10.1111/apm.12970pmid: 31127651

This study aimed to investigate the expression of programmed death receptor ligand 1 (PD‐L1) and deficient mismatch repair (dMMR) in ductal adenocarcinoma of the prostate. A tissue microarray of 32 ductal and 42 grade‐matched acinar adenocarcinomas was used. Slides were stained for PD‐L1, PD‐L2, MMR proteins, CD4 and CD8. PD‐L1 expression in tumor cells was only seen in 3% (1/34) of ductal and 5% (2/42) of acinar adenocarcinomas (p = 1.0), while PD‐L1 expression in tumor‐infiltrating immune cells was seen in 29% (10/34) of ductal and 14% (6/42) of acinar adenocarcinomas (p = 0.16). dMMR, as defined by loss of one or more of the MMR proteins, was identified in 5% (4/73) of cases, including 1 ductal and 3 acinar adenocarcinomas. There was a suggested association between infiltration of CD8+ lymphocytes and ductal subtype (p = 0.04) but not between CD4+ lymphocytes and tumor type (p = 0.28). The study shows that both dMMR and PD‐L1 expression is uncommon in tumor cells of both ductal and acinar adenocarcinoma of the prostate, while PD‐L1 expression in tumor‐infiltrating immune cells is a more common finding.

Paarnio, Karoliina; Tuomisto, Anne; Väyrynen, Sara A.; Väyrynen, Juha P.; Klintrup, Kai; Ohtonen, Pasi; Mäkinen, Markus J.; Mäkelä, Jyrki; Karttunen, Tuomo J.

doi: 10.1111/apm.12971pmid: 31132191

Toll‐like receptors (TLRs) are involved in colorectal cancer (CRC) pathogenesis. However, the significance of serum TLR concentrations in CRC is unknown. We analyzed serum TLR2 and TLR4 concentrations with ELISA in preoperative samples from 118 patients with CRC and 88 matched controls. We also assessed tissue TLR expression with immunohistochemistry and by detecting serum determinants of systemic inflammation. Most participants (>70%) had undetectable serum TLR2. The mean serum TLR4 levels were lower in patients than in controls (1.1 vs 1.8 ng/mL; p = 0.015). Undetectable TLR4 was more common in stage I (39%) than in stages II–IV (11%, p < 0.001). TLR2 or TLR4 expression in tumor cells did not correlate with serum levels, but abundant TLR2 expression in normal colon epithelium was associated with detectable serum TLR2 (p = 0.034). Undetectable serum TLR2 was linked to high modified Glasgow prognostic scores (p = 0.010), high CRP levels (p = 0.013), blood vessel invasion (p = 0.013), and tended to be associated with worse 5‐year survival (p = 0.052). In conclusion, serum TLR2 levels were inversely associated with systemic inflammation in patients with CRC. Moreover, serum TLR2 levels might depend more on normal colorectal mucosa contributions than on tumor tissue contributions. Further studies are required to assess the prognostic value of serum TLR2.

Kronvall, Göran; Baron, Sandrine; Larvor, Emeline; Rudas–Villarreal, Casandra; Hobson, Jonathan; Smith, Peter

doi: 10.1111/apm.12972pmid: 31231825

Two quite different disc contents are used for antimicrobial susceptibility testing of two fluoroquinolone drugs, flumequine and enrofloxacin, in the disc diffusion test, 30 and 5 µg, respectively. Using the SRA method, single‐strain regression analysis, we studied the impact of disc content when testing two relevant bacterial species, Aeromonas sobria and Vibrio anguillarum. There were no major differences between the antimicrobial regression lines for the two species. Wild‐type strains produced acceptable zones of inhibition over a wide range of disc contents. The flumequine 30 µg disc should be lowered in its drug content. No rational reasons for choosing so different disc contents for the two antimicrobials were apparent. At present, the choice of disc content for new antimicrobials are outside the realm of clinical microbiologists. It is recommended that reference authorities, such as EUCAST, CLSI and USCAST, are consulted for the choice of disc contents in the future.

Zhao‐Fleming, Hannah H.; Wilkinson, Jeremy E.; Larumbe, Eneko; Dissanaike, Sharmila; Rumbaugh, Kendra

doi: 10.1111/apm.12969pmid: 31127652

Necrotizing soft tissue infections (NSTIs) are associated with high morbidity and mortality and are increasing in incidence. Proper identification of the microbial causes of NSTIs is a crucial step in diagnosis and treatment, but the majority of data collected are culture based, which is biased against fastidious organisms, including obligate anaerobes. The goal of this study was to address this gap in knowledge by characterizing NSTI microbial communities through molecular diagnostics. We performed 16S rRNA sequencing on human NSTI samples and identified five genera most commonly found in NSTIs (Prevotella, Bacteroides, Peptoniphilus, Porphyromonas, and Enterococcus). We found that a >70% contribution of obligate anaerobes to the bacterial population distribution was associated with NSTI mortality, and that NSTI samples, from both survivors and non‐survivors, had an increased relative abundance of gram negative bacteria compared to those of abscess patients. Based on our data, we conclude that obligate anaerobes are abundant in NSTIs and a high relative abundance of anaerobes is associated with a worse outcome. We recommend increasing anaerobe antibiotic coverage during the treatment of NSTIs even when anaerobes are not found by traditional clinical microbiology methods, and especially when there is a clinical suspicion for anaerobe involvement.

Christensen, Anne Friesgaard; Sorensen, Grith Lykke; Junker, Kirsten; Revald, Peter; Varnum, Claus; Issa, Saida Farah; Junker, Peter; Sorensen, Flemming Brandt

doi: 10.1111/apm.12974pmid: 31233243