MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study.

BACKGROUND: Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutSα (hMSH2-hMSH6) and MutSß (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. MATERIAL AND METHODS: Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSßhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. RESULTS: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed. CONCLUSIONS: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT.

[Factors influencing the quality of clinical practice guidelines in ovarian cancer]. / Factores que influyen en la calidad de las guías de práctica clínica de cáncer de ovario.

OBJECTIVE: To identify the characteristics of the published clinical practice guidelines for the management of epithelial ovarian cancer that suggest a good methodological quality. MATERIAL AND METHODS: A literature review was performed on 25 clinical practice guidelines for epithelial ovarian cancer that were identified in different databases (MEDLINE, Guidelines International Network, National Guidelines Clearing house) published between 2007 and 2014. The quality of the guidelines was evaluated using the Appraisal of Guidelines Research and Evaluation II tool. Descriptive and bivariate analyses were performed to assess the association between the quality of the guidelines and of some of their features and their developers. RESULTS: Just under half (48%) of the guidelines were rated as low quality. Scientific societies or independent centres and private funding, or under-reporting the source of funding, were statistically associated with lower quality of clinical practice guidelines (P<.01). The guidelines developed by National Program Guidelines had a median of consistently higher scores in all domains of the Appraisal of Guidelines Research and Evaluation II, with significant differences in the definition of scope and objectives, the participation of stakeholders, the methodological rigour of development, and applicability to the context. CONCLUSIONS: Features such as the nature of the developer and funding of the guidelines are predictors of quality that should be taken into account prior to the use of the recommendations of a document.

Histopathological grading systems analysis of oral squamous cell carcinomas of young patients.

BACKGROUND: To analyze the clinicopathological profile of young patients (≤ 40 years) with oral SCC and correlate with a control group (≥ 50 years) by means of histopathological grading systems. MATERIAL AND METHODS: 14 young patients and 14 control patients were selected with similar clinical stage and tumor location. Demographic and clinical data were obtained from patient records and histological sections were evaluated according to four histopathological grading systems. Associations between categories of demographic and clinical data were performed through Chi-square test and Exact Fisher test. The survival analyzes were performed according to the Kaplan-Meier method. RESULTS: The comparison between groups showed a greater association of treatment modalities in younger patients (p=0.022), they had a higher incidence of local recurrence and regional metastasis (p=0.018) and lower disease-free survival in 5 years (p=0.069). There was no difference in 5-year overall survival among the studied groups. There was no difference in histological grading between studied groups according to the four used systems. CONCLUSIONS: This study showed that, despite tumors had similar histological grade and more therapeutic modalities were used in the young group, tumors in young patients had a higher incidence of recurrence/metastasis, showing tendency to a more aggressive behavior.

Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis.

Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X(7), encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X(7) has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores +/-2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004

Parotid mycobacteriosis is frequently caused by Mycobacterium tuberculosis in advanced AIDS.

BACKGROUND: Tuberculosis is one of the leading infectious diseases in the world, with more than 2 million new cases annually. It is one of the main causes of death of human immunodeficiency virus (HIV)-positive patients, involving multiple organs and particularly the lungs. Nevertheless there are few consistent studies about tuberculosis involving the parotid of HIV patients. The objective of this work was to describe the histological and immunohistochemical characteristics of 10 cases of mycobacteriosis involving the parotid of autopsied patients with advanced acquired immunodeficiency syndrome (AIDS), including identification of the Mycobacterium species. METHODS: Detection of 'M. tuberculosis complex' was performed by polymerase chain reaction (PCR) and ligase chain reaction (LCR) and Mycobacterium avium by PCR. RESULTS: All cases showed involvement of intraparotid lymph nodes, but the glandular parenchyma was affected in only three cases. Most of the cases (80%) presented a chronic non-caseating granulomatous inflammation, and in two cases predominated foamy macrophages, full of bacteria, and no granuloma formation. In areas of mycobacteriosis, macrophages predominated followed by TCD8, B and TCD4 lymphocytes. All cases were infected by Mycobacterium genus and 'M. tuberculosis complex' was detected in five cases by LCR and in eight by PCR, while M. avium was positive in one case only, which was also positive for M. tuberculosis. CONCLUSIONS: Parotid mycobacteriosis in advanced AIDS is characterized by intraparotid lymph node non-caseating inflammatory granulomatous lesion, caused mainly by M. tuberculosis.

Sebaceous adenoma of oral cavity: report of case and comparative proliferation study with sebaceous gland hyperplasia and Fordyce's granules.

Sebaceous adenoma (SA) is a rare solitary tumour with a predilection for the forehead and scalp. In the English literature, less than 10 cases of SA have been described in the oral cavity. The objective of this study was to examine the clinicopathologic features and evaluate the expression of epidermal growth factor and its receptor, estrogen receptor and androgen receptor in SA and in its differential diagnoses including sebaceous gland hyperplasia (SGH) and Fordyce's granules (FG). Additionally, we analysed the proliferative potential of sebaceous cells from SA, SGH and FG by measuring proliferating cell nuclear antigen (PCNA) expression and quantification of argyrophilic nuclear organizer regions (AgNORs). The SA showed many clinicopathologic similarities to cases previously reported including the biphasic population of cells, in the periphery of lobules undifferentiated basaloid cells whereas the central area was formed by mature sebocytes. SA was composed of 198 lobules of sebaceous cells, whereas SGH and FG showed a mean of 21 +/- 7.81 and 5.84 +/- 2.83, respectively. The AgNOR and PCNA indices were similar in SA, SGH and FG. These data suggest that lobule counts may be used as additional criteria in distinguishing SA of the oral cavity from other intraoral sebaceous gland lesions.