Apmis

doi: 10.1111/apm.12453pmid: N/A

Sousa, Andreia M.; Grandgenett, Paul M.; David, Leonor; Almeida, Raquel; Hollingsworth, Michael Anthony; Santos‐Silva, Filipe

doi: 10.1111/apm.12587pmid: 27538373

Mucin 1 (MUC1) has been described as the renaissance molecule due to the large set of functions it displays in both normal and neoplastic cells. This membrane‐tethered glycoprotein is overexpressed and aberrantly glycosylated in most epithelial cancers, being involved in several processes related with malignant phenotype acquisition. With a highly polymorphic structure, both in the polypeptide and glycan counterparts, MUC1 variability has been associated with susceptibility to several diseases, including cancer. Biochemical features and biological functions have been characterized upon the full‐length MUC1 protein, remaining to clarify the real impact on cell dynamics of the plethora of MUC1 isoforms. This review aims to encompass a detailed characterization of MUC1 role in carcinogenesis, highlighting recent findings in cell differentiation and uncovering new evidences of MUC1 isoforms involvement in malignant phenotype.

Soini, Ylermi

doi: 10.1111/apm.12600pmid: 27670825

Soft tissue sarcomas are a versatile group of tumors with a proposed origin from mesenchymal stem cells. During recent years, the molecular biologic mechanisms behind the histogenesis of these tumors have become clearer. In addition to translocations and other genomic changes, epigenetic mechanisms have been shown to be greatly involved in the histogenesis of sarcomas as well as other cancers. Even though the molecular mechanisms behind sarcomas appear to be more complex than previously expected, epigenetic mechanisms bring new opportunities and means for the treatment of these complex diseases.

Roos, Sara; Fyhr, Ing‐Marie; Sunnerhagen, Katharina S.; Moslemi, Ali‐Reza; Oldfors, Anders; Ullman, Michael

doi: 10.1111/apm.12586pmid: 27539941

Muscle biopsy is an essential part in the diagnostic workup in patients with suspected neuromuscular disorders. It is therefore important to be aware of morphological alterations that can be caused by systemic factors or natural ageing. Chronic limb ischaemia is frequent in elderly individuals. This study was performed to examine histopathological and mitochondrial changes in muscle in patients with chronic critical limb ischaemia. Muscle biopsy of skeletal muscle of the lower limb of patients with chronic ischaemia leading to amputation was performed and compared with muscle biopsies of healthy, age‐matched controls. The histopathological abnormalities included fibrosis, necrosis, atrophy, glycogen depletion, internal nuclei, rimmed vacuoles, fibre type grouping, cytochrome c oxidase deficient fibres, MHC‐I upregulation, and signs of microangiopathy. The only alteration found in age‐matched controls was a few cytochrome c oxidase deficient fibres. There were also increased levels of multiple mitochondrial DNA deletions in ischaemic muscles compared with controls. Critical limb ischaemia is associated with significant histopathological changes in muscle tissue and also increased levels of mitochondrial DNA deletions. Since the alterations mimic different primary myopathic changes, chronic ischaemia is important to consider as a differential diagnosis in elderly individuals, investigated with muscle biopsy for muscle disease.

Fabijanovic, Dora; Zunic, Iris; Martic, Tamara Nikuseva; Skenderi, Faruk; Serman, Ljiljana; Vranic, Semir

doi: 10.1111/apm.12588pmid: 27599467

Germ cell tumors of the testis are a heterogeneous group of neoplasms that affect male adolescents and young adults. Wnt signaling pathway components have been shown to be actively involved in normal and malignant germ cell differentiation and progression. In this study, we aimed to explore the expression patterns of the secreted frizzled‐related protein (SFRP) and Disheveled protein family (DVL) in a subset of testicular germ cell tumors. Eighty‐five formalin‐fixed, paraffin‐embedded tissue samples of the primary germ cell tumors of the testis were stained against SFRP1, SFRP3, DVL1, and DVL2 proteins using immunohistochemistry. SFRP1 and SFRP3 exhibited lower expression in both seminomas and mixed/non‐seminomatous tumors, compared with atrophic/benign tissue (p < 0.001). SFRP3 expression was lower than SFRP1 expression within the seminoma group (p = 0.004), but not within the mixed/non‐seminomatous group (p = 0.409). The majority of the tested cases (27/28, 96%) exhibited low DVL1 protein expression (median 0%, range 0–90%). In contrast, 20 out of 22 tested cases (91%) exhibited strong expression of DVL2 protein (median 80%, range 0–100%). No significant difference in DVL1 and DVL2 protein expression was observed between seminomas and mixed/non‐seminomatous tumors (p = 0.68 and 0.29). The secreted frizzled‐related protein and disheveled protein family members appear to be actively involved in the pathogenesis of primary testicular germ cell tumors.

Park, Jeong Su; Shin, Sue; Kim, Eui‐Chong; Kim, Ji Eun; Kim, Yong Beom; Oh, Sohee; Roh, Eun Youn; Yoon, Jong Hyun

doi: 10.1111/apm.12592pmid: 27546189

Persistent human papillomavirus type 16 (HPV16) is the major risk factor for cervical cancer. HPV16 intratypic variants differ in their geographical distribution and oncogenic potential. This study aimed to analyze the distribution of HPV16 variants and their association with cervical lesion histopathology in Korean women. In total, 133 HPV16‐positive cervical samples from women admitted to Seoul National University Boramae Hospital were analyzed by sequencing E6, E7, and L1 genes and the long control region (LCR), and the variant distribution according to cervical lesion grade was determined. Isolates were grouped into a phylogenetic lineage, and A1‐3, A4, C, and D sublineages were detected in 54.1, 37.8, 0.7, and 7.4% of samples, respectively. The most commonly observed LCR variations were 7521G>A (91.5%), 7730A>C (59.6%), and 7842G>A (59.6%). Furthermore, A4 or D sublineage‐positive women had a higher risk for cervical cancer than women who were positive for A1–3. Among HPV phylogenetic clusters, A1–3 was the predominant sublineage, and within A1–3, the 350G polymorphism was highly frequent. These results differed from those of previous studies in Korea and other Asian countries. The findings suggest that cervical neoplasia incidence in HPV16‐infected patients could be affected by the distribution of HPV16 variants in the population.

Leppänen, Joni; Helminen, Olli; Huhta, Heikki; Kauppila, Joonas H.; Miinalainen, Ilkka; Ronkainen, Veli‐Pekka; Saarnio, Juha; Lehenkari, Petri P.; Karttunen, Tuomo J.

doi: 10.1111/apm.12599pmid: 27677532

Doublecortin‐like kinase 1 (DCLK1) is a microtubule‐associated kinase. In murine intestine, DCLK1 marks tuft cells with characteristic microvilli, features of neuroendocrine cells and also quiescent stem cell‐like properties. The occurrence and pathological role of DCLK1‐positive cells in human intestinal mucosa is unknown. We analysed DCLK1 expression in healthy duodenal, jejunal and colorectal mucosa samples (n = 35), and in duodenal specimens from patients with coeliac disease (n = 20). The samples were immunohistochemically double‐stained with DCLK1, and synaptophysin, chromogranin A and Ki‐67. Ultrastructure of DCLK1‐expressing duodenal cells was assessed using correlative light and electron microscopy. DCLK1 expression was seen in about 1% of epithelial cells diffusely scattered through the intestinal epithelium. Electron microscopy showed that the duodenal DCLK1‐positive cells had short apical microvilli similar to neighbouring enterocytes and cytoplasmic granules on the basal side. DCLK1‐positive cells were stained with synaptophysin. The number of DCLK1‐positive cells was decreased in villus atrophy in coeliac disease. Our findings indicate that in human intestinal epithelium, DLCK1‐positive cells form a subpopulation of non‐proliferating neuroendocrine cells with apical brush border similar to that in enterocytes, and their number is decreased in untreated coeliac disease.

Singh, HariOm; Marathe, Shruti D.; Nain, Sumitra; Nema, Vijay; Angadi, Mansa; Bapat, Shradha S.; Ghate, Manisha V.; Gangakhedkar, Raman R.

doi: 10.1111/apm.12594pmid: 27538541

The HIV‐1‐induced neurological toxicity has been associated with the deficiency of matrix metalloproteinases. Tat protein of HIV up regulates MMP‐7 release and activation, leading to neurotoxicity. The SNP ‐181A>G of MMP‐7 is known to have functional effects on its promoter activity. Therefore, we aimed to evaluate the association of variants of MMP‐7 ‐181A>G gene in HIV‐associated neurocognitive disorder (HAND). In the present case–control study, we recruited 50 HIV‐infected individuals with HAND, 130 HIV‐infected individuals without HAND and 150 unrelated healthy individuals. Polymorphism for MMP‐7 ‐181A>G gene was genotyped by PCR‐RFLP method. Frequency of ‐181GG and G allele of MMP‐7 did not differ significantly between patients with HAND and without HAND (8.0% vs 13.1%, p = 0.22 and 31% vs 38.1%, p = 0.21). Individuals with ‐181 AG, ‐181GG genotype, and G allele of MMP‐7 were found to have reduced the risk of development of HAND but not significant (50.0% vs 51.9%, p = 0.09, OR = 0.54; 13.1% vs 19.0%, p = 0.33, OR = 0.71 and 38.1% vs 44.9%, p = 0.09, OR = 0.75). Individuals in early HIV disease stage having ‐181AG genotype and ‐181AG + GG combined genotype of MMP‐7 were not associated with the development of HAND (OR = 1.27, p = 0.25 and OR = 1.25, p = 0.17). Tobacco and alcohol consumption among individuals with any genotype of MMP‐7 was not associated with the risk of development of HAND. In conclusion, individuals with ‐181GG genotype and G allele had no impact on susceptibility to the development of HAND and its severity.

Cavanagh, Jorunn Pauline; Wolden, Runa; Heise, Philipp; Esaiassen, Eirin; Klingenberg, Claus; Aarag Fredheim, Elizabeth G.

doi: 10.1111/apm.12591pmid: 27599662

The primary aim of this study was to determine antimicrobial resistance in coagulase‐negative staphylococci (CoNS) from healthy adults in the community. Healthy adults (n = 114) were swabbed on six body sites; both armpits, both knee pits and both sides of the groin. Species determination was performed using Matrix Assisted Laser Desorption Ionization – Time of Flight (MALDI‐TOF) and susceptibility testing for 11 relevant antimicrobials was performed by the disc diffusion method and minimal inhibitory concentration gradient test. In total, 693 CoNS isolates were identified. Susceptibility testing was done on 386 isolates; one CoNS from each species found on each participant from the different body sites. The prevalence of antimicrobial resistance in the CoNS isolates were; erythromycin (24.6%), fusidic acid (19.9%), tetracycline (11.4%), clindamycin (7.8%), gentamicin (6.2%) and cefoxitin (4.1%). Multidrug resistance was observed in 5.2% of the isolates. Staphylococcus epidermidis and S. hominis were the first and second most prevalent species on all three body sites. We conclude that CoNS isolates from healthy adults in the community have a much lower prevalence of antimicrobial resistance than reported in nosocomial CoNS isolates. Still, we believe that levels of resistance in community CoNS should be monitored as the consumption of antimicrobials in primary care in Norway is increasing.

Kirdar, Sevİn; Sener, Asli Gamze; Cengİz, Merve; Aydin, Nerİman

doi: 10.1111/apm.12593pmid: 27670736

The prevalence of autoantibody in the patients with chronic hepatitis C infection, and the relationship between the autoantibodies and HCV genotypes were investigated in this study. One hundred and eight anti‐HCV positive and 86 anti‐HCV negative patients were included in the study. Anti‐HCV were studied by enzyme immunassay (EIA). HCV RNA was determined by real time polymerase chain reaction (PCR) and HCV genotypes were determined by a reverse‐line blot hybridization. Anti‐nuclear antibodies (ANA), anti‐smooth muscle antibodies (ASMA), Anti‐mitochondrial antibodies (AMA), liver kidney microsomal antibodies (LKM) were detected by indirect immunofluorescence assay. Among patients, 13 (12.03%) of 108 were positive for at least one autoantibody. The positivity was not observed in control group. The most prevalent autoantibody in anti‐HCV positive group was ANA. ANA was positive in six HCV patients with genotype 1. In HCV patients with genotype 1, the frequencies of ANA, ASMA, AMA and LKM1 were six, two, three and one, respectively. In HCV patients with genotype 2, ANA was positive one patient and ASMA, AMA and LKM1 were not detected in HCV patients with genotype 2. In conclusion, the autoantibodies in patients with chronic hepatitis C in the study were low as compared to those reported in previous studies.