HMGA2 is a Specific Immunohistochemical Marker for Pleomorphic Adenoma and Carcinoma ex-Pleomorphic Adenoma

Abstract

Aims

Accurate classification of salivary gland neoplasms may be challenging due to morphologic overlap, particularly in small biopsies. Recurrent translocations involving High Mobility Group A2 (HMGA2) are present in a subset of pleomorphic adenoma (PA) and carcinoma ex-pleomorphic adenoma (CA ex-PA). We evaluated immunohistochemical HMGA2 expression in 225 salivary gland tumors including 56 PAs, 37 CA ex-PAs and 132 potential histologic mimics to determine its diagnostic utility.

Methods and results

HMGA2 expression was identified in 19 PAs (33.9%) and 9 CA ex-PAs (24.3%). Expression was strong and diffuse throughout all PAs and 4 of 9 positive CA ex-PA cases. In 5 CA ex-PAs, HMGA2 showed weak-to-strong multifocal staining within the carcinomatous component, with strong, diffuse HMGA2 expression in residual PA. Among histologic mimics: 6 de novo salivary duct carcinomas (28.5%), 3 epithelial-myoepithelial carcinomas (33.3%) and 1 case each of myoepithelioma and basal cell adenoma expressed HMGA2. FISH for HMGA2 rearrangement performed on a subset of tumors showed diffuse HMGA2 expression in PA and CA ex-PA was frequently associated with rearrangement of the HMGA2 locus, while cases of de novo salivary duct carcinoma, or CA ex-PA with limited or no HMGA2 expression, had an intact HMGA2 locus.

Conclusions

HMGA2 expression is a highly specific (96.2%), but low sensitivity (29.8%), marker for PA and CA ex-PA when compared to histologic mimics, and is frequently associated with rearrangement of the HMGA2 locus.

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Studying the association between methylene tetrahdrofolate reductase (MTHFR) 677 gene polymorphism, cardiovascular risk and lichen planus

Abstract

Background

There is a reported relation between hyperhomocysteinemia and lichen planus (LP). An increase in homocysteine (Hcy) and the risk of cardiovascular disease (CVD) in patients with methylenetetrahydrofolate reductase (MTHFR) mutation has been described

Objective

To detect MTHFR (C677T) gene polymorphism, and to find its association with CVD risk, Hcy and folic acid levels in patients with LP

Methods

This hospital-based case-control study included 110 patients with LP; 70 with cutaneous LP (CLP) and 40 with oral LP (OLP). 120 age and sex matched healthy subjects were used as controls. Three ml venous blood sample was taken for detection of MTHFR gene polymorphism by PCR-RFLP technique and for measurement of the lipid profile. Hcy and folic acid were measured by ELISA. Hypertension was evaluated

Results

There were significantly higher prevalence of hypertension with higher Hcy, triglycerides and cholesterol levels and lower folic acid and HDL levels among patients’ groups. Hypertension with higher Hcy and cholesterol levels together with lower folic acid and HDL levels have been found in OLP when compared to CLP. Patients showed a significant higher percentage of the MTHFR 677 TT genotype (P=0.003) and of the MTHFR 677 T allele (P=0.042) compared to controls. Moreover, there was higher a prevalence of MTHFR 677 T allele in patients with CLP.

Conclusion

MTHFR 677 gene polymorphism may be a risk factor for the development of the LP, and to predispose these patients to higher risk of CVD.

This article is protected by copyright. All rights reserved.

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Development of a financially viable model for the management of mandibular fractures as day cases in a level 1 major trauma centre

Publication date: Available online 29 April 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): J. Haq, J. Olding, S. Chegini, C. Huppa, R. Bentley, K. Fan
There is a subgroup of patients with mandibular fractures who could safely and effectively be managed in an outpatient day-care unit. Suitability depends on medical, social, and operative factors, and identification of the correct criteria will govern management after that in the emergency department. Reduced use of beds would lead to less money being spent on emergency treatment, and increased capacity for elective surgery. The aims of this study were to identify a group of patients with mandibular fractures whose duration of operation and period of recovery would be suitable for treatment in the day-care unit, and to evaluate the potential financial benefits. Inpatients were assessed for day surgery using medical, social, and surgical criteria. Each patient’s suitability for discharge was assessed two, three, and five hours postoperatively. A financial feasibility study was made retrospectively on a larger sample of patients with mandibular fractures. The discharge criteria from the day-care unit were fully met by 26/40 patients at five hours postoperatively, mean (range) duration of operation was 145 (40–285) minutes, and mean (SD) Mandibular Injury Severity Score was 13 (3), range 7–20. When all the criteria were combined (n=100), 12 of the patients were suitable for day care. With 24 bed-day savings/100 patients, potential earnings would increase to around £80 000/year at this hospital. In conclusion, we have identified a group of patients who were suitable for management of mandibular fractures in the day-care unit. Considerable cost savings are anticipated.

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Use of couplers for vascular anastomoses in 601 free flaps for reconstruction of defects of the head and neck: technique and two-year retrospective clinical study

Publication date: Available online 29 April 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): A. Assoumane, L. Wang, K. Liu, Z.-J. Shang
We describe our experience with the use of 854 couplers for venous or arterial anastomoses, or both, in 601 free flaps for reconstruction of defects of the head and neck. We reviewed 601 patients who had had free flaps (with the microvascular anastomoses being made with couplers in 519) between July 2013 and December 2015. Personal details, and clinical data including the site of the defect, the tumour excised, the types of flaps, the size of the couplers, the method of anastomosis (venous or arterial) in which the coupler was used, and postoperative complications were recorded. There were 417 men (69%) and 184 women (31%), mean (range) age 53 (13–91) years. Four types of flaps were used: anterolateral thigh flap (n=232), radial forearm flap (n=223), fibula free flap (n=78), and iliac crest flap (n=68). The sizes of couplers ranged from 1–4mm, most being 2mm (n=158), followed by 1.5mm (n=122). The recipient vessels used included a single vein (n=348), two veins (n=406), and both vein and artery (n=100). The overall success rate was 99%, and eight patients required resuture, which was successful in each case. This retrospective study shows that a coupler is easy to use, and is a reliable and time-saving technique for microvascular anastomosis. However, the disadvantage is the cost of the instrument, which in less developed countries will limit its use.

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Linoleic acid induces migration and invasion through FFAR4- and PI3K-/Akt-dependent pathway in MDA-MB-231 breast cancer cells

Abstract

                <p>An increased risk of developing breast cancer has been associated with high levels of dietary fat intake. Linoleic acid (LA) is an essential fatty acid and the major <em>ω</em>-6 polyunsaturated fatty acid in occidental diets, which is able to induce inappropriate inflammatory responses that contribute to several chronic diseases including cancer. In breast cancer cells, LA induces migration. However, the signal transduction pathways that mediate migration and whether LA induces invasion in MDA-MB-231 breast cancer cells have not been studied in detail. We demonstrate here that LA induces Akt2 activation, invasion, an increase in NFκB–DNA binding activity, miR34a upregulation and miR9 downregulation in MDA-MB-231 cells. Moreover, Akt2 activation requires EGFR and PI3K activity, whereas migration and invasion are dependent on FFAR4, EGFR and PI3K/Akt activity. Our findings demonstrate, for the first time, that LA induces migration and invasion through an EGFR-/PI3K-/Akt-dependent pathway in MDA-MB-231 breast cancer cells.</p><br /><br />

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Haplotypes of the RANK and OPG genes are associated with chronic arthralgia in individuals with and without temporomandibular disorders

Publication date: Available online 29 April 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): L.L. Bonato, V. Quinelato, R. Borojevic, A.R. Vieira, A. Modesto, J.M. Granjeiro, R. Tesch, P.L. Casado
The aim of this study was to evaluate the association between genetic polymorphisms and the comorbid presence of chronic systemic arthralgia in patients with articular temporomandibular disorders (TMD). Subjects were evaluated for the presence of TMD and asked about the presence of chronic joint pain. Four groups were included in the study: articular TMD and systemic arthralgia (n=85), no articular TMD and systemic arthralgia (n=82), articular TMD and no systemic arthralgia (n=21), no articular TMD and no systemic arthralgia (control, n=72). A total of 14 single nucleotide polymorphisms in the OPG, RANK, and RANKL genes were investigated. In the statistical analysis, a P-value of <0.05 was considered significant. For the OPG gene, an association was observed between the group with chronic arthralgia and joint TMD and the control group (P=0.04). There was also a tendency towards an association of the haplotype CGCCAA with an increased risk of developing chronic joint pain, even in the absence of TMD (P=0.06). For the RANK gene, the AGTGC haplotype was associated with the lowest risk of presenting chronic joint pain in individuals without TMD (P=0.03). This study supports the hypothesis that changes in the OPG and RANK genes influence the presence of chronic joint pain in individuals with and without TMD.

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Comparison and evaluation of risk factors for meningeal, pleural, and extrapleural solitary fibrous tumors: A clinicopathological study of 92 cases confirmed by STAT6 immunohistochemical staining

Publication date: Available online 29 April 2017
Source:Pathology – Research and Practice
Author(s): Ji Min Kima, Yoon-La Choia, Hyung Kyu Parka
Solitary fibrous tumors (SFTs) are an uncommon type of mesenchymal tumors that are presumably fibroblastic in nature. SFTs are translocation-associated neoplasms that can be consistently diagnosed through the evaluation of NAB2/STAT6 gene fusion. Currently, SFTs have a different grading system and criteria according to their primary sites, and the differences and similarities in SFTs according to their primary sites are still poorly understood. Therefore, we compared SFTs according to their primary sites and histologic appearance, and validated the current grading system of SFTs.A total of 92 patients (with 15 meningeal, 30 pleural, and 37 extrapleural SFTs) were evaluated. The patients with pleural SFTs (mean age: 60.2 years) showed a significantly increased age at diagnosis. Tumors with hemangiopericytoma-predominant morphology had significantly higher grades in the evaluation of several risk factors such as cellularity (P<0.001), pleomorphism (P=0.001), and mitotic activity (P<0.001). Consequently, hemangiopericytoma (HPC)-predominant tumors had a significantly higher recurrence rate. The meningeal SFT group had significantly higher proportion of the HPC-predominant histologic phenotype compared with pleural or extrapleural SFTs (66.67% vs. 5.00% or 18.92%, respectively; P<0.001). Consequently, meningeal SFTs showed significantly higher recurrence rates compared with pleural or extrapleural SFTs (33.33% vs. 12.50% or 2.70%, respectively; P=0.009). Regarding the evaluation of risk factors, a tumor size ≥10cm (P=0.017), a mitotic index ≥4/10 high power fields (HPFs) (P=0.001), high tumor cellularity (P=0.003), high nuclear pleomorphism (P=0.005), and tumor necrosis (P=0.004) were associated with both recurrence and disease-specific mortality. Upon evaluation of the usefulness of the criteria using previously described factors, the predictive model was on the borderline of validation. Of the five factors indicated in the log rank test, only a mitotic index ≥4/10 HPFs remained a significant factor in the multivariate Cox model.

Graphical abstract

image

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Expression of miR-23a by Apoptotic Regulators in Human Cancer: A Review.

Related Articles

Expression of miR-23a by Apoptotic Regulators in Human Cancer: A Review.

Cancer Biol Ther. 2017 Apr 28;:0

Authors: Roufayel R, Kadry S

Abstract

MicroRNAs play fundamental roles in mammalian development, differentiation and cellular homeostasis by regulating essential processes such as proliferation, migration, metabolism, migration and cell death. These small non-coding RNAs are also responsible in RNA silencing, and in many developmental and pathological processes. Not surprisingly, miR-23a misexpression contributes to numerous diseases including cancer where certain miRNA genes have been classified as either oncogenes or tumor suppressor genes. Since a single microRNA is capable of targeting a large number of mRNA sequences, de-regulated miRNA expression has the ability to alter various transcripts and activate a wide range of cancer-related pathways. This review article documents reduced levels of mature miR-23a in various tumors, primarily due to epigenetic silencing or alterations in biogenesis pathways. Moreover, inhibition of miR-23a in stressed cells represent a general mechanism for inducing apoptosis and these microRNAs are showed to be regulated by molecular chaperon HSP70. Microarray expression analysis of miRNA overexpression or depletion is now used in the characterization of cancer development pathways and as a biomarker for early cancer detection.

PMID: 28453394 [PubMed – as supplied by publisher]

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The reliability of the Adelaide in-shoe foot model

Publication date: July 2017
Source:Gait & Posture, Volume 56
Author(s): Chris Bishop, Susan Hillier, Dominic Thewlis
Understanding the biomechanics of the foot is essential for many areas of research and clinical practice such as orthotic interventions and footwear development. Despite the widespread attention paid to the biomechanics of the foot during gait, what largely remains unknown is how the foot moves inside the shoe. This study investigated the reliability of the Adelaide In-Shoe Foot Model, which was designed to quantify in-shoe foot kinematics and kinetics during walking. Intra-rater reliability was assessed in 30 participants over five walking trials whilst wearing shoes during two data collection sessions, separated by one week. Sufficient reliability for use was interpreted as a coefficient of multiple correlation and intra-class correlation coefficient of >0.61. Inter-rater reliability was investigated separately in a second sample of 10 adults by two researchers with experience in applying markers for the purpose of motion analysis. The results indicated good consistency in waveform estimation for most kinematic and kinetic data, as well as good inter-and intra-rater reliability. The exception is the peak medial ground reaction force, the minimum abduction angle and the peak abduction/adduction external hindfoot joint moments which resulted in less than acceptable repeatability. Based on our results, the Adelaide in-shoe foot model can be used with confidence for 24 commonly measured biomechanical variables during shod walking.

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Urothelial carcinoma involving the ureteral orifice: A clinicopathologic analysis of 93 cases

Publication date: Available online 29 April 2017
Source:Human Pathology
Author(s): Anand C. Annan, Keith A. Stevens, Adeboye O. Osunkoya
Although tumors involving the bladder and ureter have been well described, there are only few studies in the pathology literature specifically analyzing tumors involving the ureteral orifice (UO). A search was performed for biopsy and resection specimens (transurethral resection, radical cystectomy/cystoprostatectomy, nephroureterectomy and bladder cuff resection) of urothelial carcinoma (UCa) involving the UO. Ninety three cases were identified. Sixty two (67%) patients were male. Mean patient age was 71years (range: 43–91years). Forty two of 93 (45%) cases were invasive UCa (41 high-grade UCa; 1 low-grade UCa); 17/42 (40%) were invasive into muscularis propria. Tumor laterality was as follows: right side, 43 (46% of cases); left side, 42 (45%); bilateral, 4 (4.5%); and in 4 cases (4.5%) the laterality was not specified by the Urologist. Seven cases of UCa with variant histology were also identified. Five patients had lymph node (LN) metastasis at the time of resection, and another 3 presented with LN or distant metastasis after resection (range: 4–38months). Although this study focused primarily on the index tumor involving the UO (Group 1 cases are those with only UO involvement), in 70/93 (75%) cases (Group 2 cases), at least one other tumor was located at another site within the bladder. The fact that the majority of cases (75%) had tumors located at other sites of the bladder, emphasizes that careful examination of the UO needs to be performed by both Urologists and Pathologists when examining cases of UCa of the bladder.

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