cfDNA Methylation Profiles and T-Cell Differentiation in Women with Endometrial Polyps.

DNA methylation is a part of the regulatory mechanisms of gene expression, including chromatin remodeling and the activity of microRNAs, which are involved in the regulation of T-cell differentiation and function. However, the role of cfDNA methylation in T-cell differentiation is entirely unknown. In patients with endometrial polyps (EPs), we have found an imbalance of T-cell differentiation and an aberrant cfDNA methylation profile, respectively. In this study, we investigated the relationship between cfDNA methylation profiles and T-cell differentiation in 14 people with EPs and 27 healthy controls. We found that several differentially methylated genes (DMGs) were associated with T-cell differentiation in people with EPs (ITGA2-Naïve CD4, r = -0.560, p = 0.037; CST9-EMRA CD4, r = -0.626, p = 0.017; and ZIM2-CM CD8, r = 0.576, p = 0.031), but not in healthy controls (all p > 0.05). When we combined the patients' characteristics, we found a significant association between ITGA2 methylation and polyp diameter (r = 0.562, p = 0.036), but this effect was lost when adjusting the level of Naïve CD4 T-cells (r = 0.038, p = 0.903). Moreover, the circulating sex hormone levels were associated with T-cell differentiation (estradiol-Naïve CD4, r = -0.589, p = 0.027), and the cfDNA methylation profile (testosterone-ZIM2, r = -0.656, p = 0.011). In conclusion, this study has established a link between cfDNA methylation profiles and T-cell differentiation among people with EPs, which may contribute to the etiology of EPs. Further functional studies are warranted.

Circulating PD1+Vδ1+γδ T Cell Predicts Fertility in Endometrial Polyp Patients of Reproductive-Age.

Clinically, immune cell function is correlated with pathogenesis of endometrial polyp (EP) and infertility of women of reproductive-age. However, the underlying immune cell hallmark in EP patients remains unclear. Here, we focused on analyzing circulating immune cells, and attempted to reveal the correlation between peripheral immune cell functional phenotypes and fertility in EP patients. Through comparison of circulating CD4+/CD8+ T cells, NK cells, and γδ T cells between 64 EP patients and 68 healthy females, we found that γδ T cells, but not CD4+/CD8+ T cells and NK cells, were immunologically correlated with conception rate and conception interval time. Specifically, total γδ T cells and the Vδ1+PD1+ γδ T subpopulation decreased whereas the Vδ1/Vδ2 ratio increased in EP patients compared to healthy controls. Moreover, the patients with the higher Vδ1/Vδ2 ratio (median value equals 1.04) had a poorer fertility and longer interval time of conception (210 days versus 158 days for control). Meanwhile, higher Vδ1+PD1+ γδ T cell proportion (median equals 15.7) was positively correlative with both higher conception rate and shortened median conception interval time (130 days for Vδ1+PD1high group versus 194 days for Vδ1+PD1low group). Notably, in healthy controls, both Vδ1/Vδ2 ratio and Vδ1+PD1+ γδ T cell proportion correlated with pregnancy rate oppositely, comparing to EP patients. Together, our results suggested that imbalanced γδ T cell population occurred in EP patients, and that Vδ1/Vδ2 ratio and PD-1 expression of Vδ1+ γδ T cells could be potentially developed into valuable predictors for fertility in EP patients.

Schwannoma of the sinonasal tract: case report with review of the literature.

Schwannomas of the sinonasal tract are rare, accounting for <4% of head and neck schwannomas. We report the case of a 61-year-old male who presented with unilateral nasal symptoms. Examination and imaging revealed a unilateral polyp at the level of the middle turbinate, with an initial biopsy suggestive of an inflammatory polyp. Due to the persistence of the patient's symptoms and his polyp despite medical therapy, endoscopic nasal polypectomy was performed. The histology surprisingly showed a schwannoma. No further interventions were carried out, and the patient remains disease-free 6 months postoperatively. A review of the literature comprising 60 cases is included. An optimal clinical approach to the investigation and management of schwannomas of the sinonasal tract is subsequently discussed.

Microfilaria-dependent thoracic pathology associated with eosinophilic and fibrotic polyps in filaria-infected rodents.

BACKGROUND: Pulmonary manifestations are regularly reported in both human and animal filariasis. In human filariasis, the main known lung manifestations are the tropical pulmonary eosinophilia syndrome. Its duration and severity are correlated with the presence of microfilariae. Litomosoides sigmodontis is a filarial parasite residing in the pleural cavity of rodents. This model is widely used to understand the immune mechanisms that are established during infection and for the screening of therapeutic molecules. Some pulmonary manifestations during the patent phase of infection with L. sigmodontis have been described in different rodent hosts more or less permissive to infection. METHODS: Here, the permissive Mongolian gerbil (Meriones unguiculatus) was infected with L. sigmodontis. Prevalence and density of microfilariae and adult parasites were evaluated. Lungs were analyzed for pathological signatures using immunohistochemistry and 3D imaging techniques (two-photon and light sheet microscopy). RESULTS: Microfilaremia in gerbils was correlated with parasite load, as amicrofilaremic individuals had fewer parasites in their pleural cavities. Fibrotic polypoid structures were observed on both pleurae of infected gerbils. Polyps were of variable size and developed from the visceral mesothelium over the entire pleura. The larger polyps were vascularized and strongly infiltrated by immune cells such as eosinophils, macrophages or lymphocytes. The formation of these structures was induced by the presence of adult filariae since small and rare polyps were observed before patency, but they were exacerbated by the presence of gravid females and microfilariae. CONCLUSIONS: Altogether, these data emphasize the role of host-specific factors in the pathogenesis of filarial infections.

Tn and Sialyl-Tn antigens in canine gastric tissues.

Malignant transformation is often associated with abnormal protein glycosylation expressed, amongst others, by the accumulation of simple mucin-type carbohydrates namely Tn and Sialyl-Tn (STn) antigens. These are usually limited in normal tissues and their increased expression has been associated with cancer progression and poor prognosis. This study aims to evaluate the role of Tn and STn antigens in the neoplastic transformation of the canine gastric mucosa and to correlate their putative immunoexpression alterations with some pathological features. Tn and STn antigens expression were immunohistochemically evaluated in canine normal gastric mucosa (n = 3), gastric polyps (n = 9) and gastric carcinomas (n = 25), neoplastic emboli (n = 12) and metastases (n = 8). In normal gastric mucosa, Tn antigen was detected in the gastric epithelial cells, while STn antigen was absent. Similarly, all gastric polyps expressed Tn antigen, but none displayed STn antigen immunostaining. In carcinomas, Tn antigen was expressed in 96% of the cases and STn antigen in 68% of the neoplasms. STn antigen was significantly higher in carcinomas compared with normal mucosa (P < .05). No correlation was found between each antigen and the different subtypes of tumours according to WHO classification, tumour differentiation, lymph vascular invasion or metastasis. All neoplastic emboli expressed both antigens, and the expression score was similar or higher than that displayed by the neoplastic cells of the primary tumour. The high prevalence of STn antigen in gastric carcinomas compared with normal mucosa highlights the cancer-associated nature of this antigen. Our results link STn antigen expression to neoplastic transformation and suggest that it may be a useful marker of gastric cancer progression in dogs.

Polypoidal Choroidal Vasculopathy Associate With Diminished Regulatory T Cells That Are Polarized Into a T Helper 2-Like Phenotype.

Purpose: To investigate possible roles of T helper (Th) cells, regulatory T cells (Tregs), and the recently mapped Th-like Tregs in patients with polypoidal choroidal vasculopathy (PCV). Methods: In this prospective case-control study, we obtained fresh venous blood from patients with PCV (n = 24), age-matched healthy controls (n = 32), and patients with neovascular AMD (n = 45). All participants underwent a comprehensive ocular examination including fluorescein and indocyanine green angiography for where retinal disease was suspected. Using flow cytometry, we identified Th subsets, Tregs, and Th-like Tregs. Plasma samples were stored at -80°C to investigate plasma cytokines of interest. Results: Compared to healthy controls, patients with PCV had lower percentages of Tregs (8.7% ± 2.8% vs. 7.3% ± 1.7%, P = 0.027), which were significantly more Th2-like polarized (42.6% ± 13.3% vs. 50.5% ± 13.0%, P = 0.029). These changes differed from that observed in neovascular AMD, which compared to healthy controls had fewer Th1/Th17 cells (3.6% ± 2.7% vs. 2.4% ± 2.5%, P = 0.049), comparable Treg levels, and no distinct polarization of Th-like Tregs. Because of these findings, we measured plasma IL-4 and IL-33 levels. Plasma IL-33 in patients with PCV (median 0.30 pg/mL) was twice as high compared to healthy controls (median 0.16 pg/mL; P = 0.037). Conclusions: PCV associate with diminished Tregs that are polarized more into a Th2-like phenotype. This is correlated to IL-33 levels, which we also find increased in patients with PCV. Our findings suggest a possible role for Th2-like Tregs and IL-33 in PCV.

Concomitant p53 and PTEN immunoexpression to predict the risk of malignancy in endometrial polyps.

The aim of this retrospective cross-sectional study was to assess the usefulness of phosphase and tensin homolog deleted on chromosome 10 (PTEN) and p53 protein immunoexpression in predicting the risk of malignancy in endometrial polyps. The study was conducted at tertiary public hospital, university teaching center, and private practice clinic.A total of 159 patients with endometrial polyps who underwent hysteroscopic polypectomy between January 2010 to December 2014 were included. p53 and PTEN immunoexpression were assessed in histologic endometrial polyp samples. Patients were allocated into 2 groups: group A, endometrial polyps without atypia (120), and group B, endometrial polyps with atypia (39), which were subdivided into A1 (80) and B1 (21) = p53-/PTEN+ immunostaining; A2 (20) and B2 (11) = p53+/PTEN+; A3 (14) and B3 (4) = p53+/PTEN-; A4 (6) and B4 (3) = p53-/PTEN-.There was no significant difference between groups regarding clinical and epidemiologic parameters, except for age. Neoplasia incidence within groups was higher when at least 1 marker was abnormally stained (in group A, P = .0089, odds ratio [OR] = 13.94 [1.62; 120.27]; in group B, P = .0255, OR 12.73 [1.38; 117.27]). Overall neoplasia incidence was higher in group B than in group A (20.5% vs 5.8%; P = .0113). Malignant neoplasia was found more frequently in patients with p53+ (P = .0006, OR = 7.67 [2.30; 25.54]) and PTEN- (P = .0043; OR = 5.43 [1.77; 16.61]).Immunohistochemical analysis using p53 and PTEN as markers, either alone or concomitantly, can be useful to predict malignant transformation in cases of endometrial polyps.

Macrophages in patients with recurrent endometrial polyps could exacerbate Th17 responses.

Endometrial polyps (EPs) are outgrowths in the endometrium with unknown etiology. The fact that EPs can often recur after surgical removal suggests that EPs are not induced by random events but by continuous or recurrent processes in patients. We previously demonstrated that the risk of EP development was positively associated with overactive Th17 responses. However, the requirements of Th17 upregulation are yet unclear. Here, we recruited 26 women with symptomatic EP and 24 without EP, and peripheral mononuclear cells were harvested for the examination of circulating immunity. Compared to controls without EP, the patients with symptomatic EP presented significantly elevated levels of monocyte activation. The circulating monocytes from patients secreted higher levels of tumor necrosis factor (TNF), interleukin (IL)-1ß, IL-6 and IL-23 directly ex vivo and with LPS stimulation. In memory CD4+ T cells, monocytes were not required for IL-17 expression, but the presence of activated monocytes significantly increased the secretion of IL-17. In naive CD4+ T cells, activated monocytes were required for significant IL-17 secretion and RORC transcription. Interestingly, the monocytes from EP individuals were significantly more potent in promoting Th17 differentiation from naive CD4+ T cells than the monocytes from controls. Furthermore, we showed that monocyte-mediated Th17 differentiation required the secretion of TNF, IL-1ß and IL-6. Together, this study demonstrated activated monocytes supported Th17 inflammation in patients with EP.

Endotyping of Chronic Rhinosinusitis With and Without Polyp Using Transcription Factor Analysis.

Inflammation of the nose and paranasal sinus or rhinosinusitis (RS) is a significant global health problem that is both very common and very costly to treat. Previous reports reveal variability in histology and mechanism of inflammation in patients with chronic rhinosinusitis with and without polyp (CRScNP and CRSsNP, respectively). There are various methods and hypothesis that try to explain this variability. Accordingly, the aim of this study was to investigate the incidence of each type of sinonasal inflammation among patients diagnosed with CRScNP or CRSsNP using transcription factor analysis (TFA). This study included mucosa specimens from nose/paranasal sinuses from patients with chronic rhinitis (CR), CRSsNP, or CRScNP that were obtained at the Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during the June 2009 to May 2012 study period. TFA was employed to measure the following transcription factors: T-box transcription factor (T-bet) for Th1, GATA binding protein 3 (GATA-3) for Th2, retinoic acid-related orphan receptor C (RORC) for Th17, and forkhead box P3 (FOXP3) for Treg. Forty-one subjects (22 males, 19 females) were enrolled, with a mean age of 45.93 ± 13 years. Twenty-six patients were diagnosed with CRScNP, 7 with CRSsNP, and 8 with CR (controls). The majority of CRScNP specimens (76.9%) had eosinophil count greater than 100 cells/high-power field (HPF). Mean eosinophil count was 930.08 ± 1,399 cells/HPF (range: 17-5,570). Th2 transcription factor (GATA-3) was statistically significantly higher in the CRScNP group than in the CRS and control groups (p < 0.001); whereas, Treg transcription factor (FOXP3) was statistically significantly lower in the CRScNP group than in the CRSsNP and control groups (p < 0.001). The transcription factors for Th1 and Th17 (T-bet and RORC, respectively) were not significantly different among the three groups. The result of transcription factor analysis revealed hyperfunction of Th2 in patients with CRScNP, which might result in hypereosinophilic infliltration in the polyps. One explanation for this finding is the decreased activity of Treg. Although environment-host interaction is the most probable hypothesis, the etiology of aberrant adaptive immunity needs to be elucidated.

CD4+ T cell imbalance is associated with recurrent endometrial polyps.

Endometrial polyps (EPs) are localized benign overgrowths at the endometrium, with currently unknown aetiology and pathogenesis. Although symptoms of EP can be alleviated or resolved by hysteroscopic polypectomy, a significant fraction of individuals develop recurrent EPs after initial EP removal. In rare cases, EPs may also undergo malignant transformation. In-depth understanding of the mechanisms that are involved in EP development is urgently needed. Recent works indicate that dysregulations in the immune system participate in the development of a variety of symptoms, such as aging, obesity and hypertension, many of which are EP risk factors. Based on these discoveries, we investigated the cellular immune system in premenopausal women with and without EP. Compared to EP-free controls, the women with EP presented significantly higher RORC expression but unchanged TBX21 and FOXP3 expression in the circulating CD4+ T cells. When stimulated with PMA/ionomycin, CD4+ T cells from women with EP presented significantly higher interferon (IFN)-γ and interleukin (IL)-17 secretion, and lower transforming growth factor (TGF)-ß secretion. Hysteroscopic polypectomy did not significantly alter the composition of CD4+ T cells, as the women with EP presented a similar upregulation of Th17 inflammation and a downregulation of regulatory T cell (Treg) response postoperatively. Notably, in women that developed recurrent EP, the CD4+ T cells presented higher preoperative and postoperative RORC, IFN-γ, and IL-17 expression, as well as lower postoperative FOXP3 and TGF-ß expression, than hysteroscopic polypectomy-treated women without EP recurrence. These data demonstrated an association between CD4+ T cell imbalance and recurrent EP development.

The role of macrophages in the differentiation process of ureteral polyps.

Objective To evaluate the role of macrophage infiltration in the differentiation process of ureteral polyps and cancers. Methods This retrospective immunohistochemical study analysed archival samples of pathologically-confirmed specimens of low- and high-grade ureteral cancer, ureteral papilloma and ureteral polyps. The samples were immunohistochemically stained for cluster of differentiation (CD)4, CD8, CD16, CD25, CD56 and CD68 using immunofluorescence in order to identify different T-lymphocyte populations and macrophages. Results A total of 70 specimens were included in the analysis: 21 specimens of ureteral cancer, 17 specimens of ureteral papilloma, and 32 specimens of ureteral polyps. The largest proportion of CD4+CD25+ regulatory T cells was observed in the low-grade ureteral cancer group and almost none were observed in ureteral papillomas. The largest proportion of CD8+ cytotoxic T-lymphocytes was observed in the ureteral polyps. The largest proportion of CD56+ natural killer cells was detected in the ureteral polyps, with very low levels observed in the other three groups. The largest proportion of CD16+CD68+ macrophages was observed in the high-grade ureteral cancer group, which was significantly higher than that observed in the ureteral papillomas. Conclusions This study revealed that CD16+CD68+ macrophages appear to participate in ureteral neoplastic transformation.

Unique invariant natural killer T cells promote intestinal polyps by suppressing TH1 immunity and promoting regulatory T cells.

CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APCMin/+ mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4+, NK1.1- CD44int, and PD-1lo, and they were negative for the NKT cell transcription factor promyelocytic leukemia zinc-finger. The absence of iNKT cells was associated with a reduced frequency of regulatory T (Tregs) cells and lower expression levels of FoxP3 protein and transcript uniquely in the polyps, and a switch to an inflammatory macrophage phenotype. Moreover, in iNKT cell-deficient APCMin/+ mice, expression of T-helper (TH) 1-associated genes, such as IFN-γ and Nos2, was increased in polyps, concomitantly with elevated frequencies of conventional CD4+ and CD8+ T cells in this tissue. The results suggest that a population of regulatory iNKT cells locally promote intestinal polyp formation by enhancing Treg cells and immunosuppression of antitumor TH1 immunity.

ENDOMETRIAL POLYPS IN WOMEN OF REPRODUCTIVE AGE: CLINICAL AND PATHOGENE-TIC VARIATIONS.

The aim of the study was to study the relationship between the morphofunctional characteristics of the endometrium, hormonal homeostasis and microbiocenosis of the reproductive system in patients with endometrial polyps. The study involved 130 patients aged 18-35 years: 34 patients with endometrial polyps, 30 patients with micropolyps, 36 patients with endometrial polyps and micropolyps, 30 healthy women of the control group. Hysteroscopy was performed for women who had been suspected for endometrial polyps and who had infertility or repeated recurrent miscarriages. Endometrial samples from healthy women were obtained by aspiration biopsy. The endometrial sections were immunostained with monoclonal antibodies against the specific markers of plasmacytes (CD138), NK cells (CD56, CD16), pan-leukocytes (CD45), macrophages (CD68), cellular marker for proliferation (Ki-67), ER, PR. Bacteriological examination of the endometrium was performed by PCR and by cultivating aerobic and anaerobic microorganisms on special growth media. In all groups of women the content in blood serum for 3-5 day of a menstrual cycle of gonadotropic hormones (FSH, LH) and sex steroid hormones (estradiol, prolactin) was studied, for 21 days of a cycle estimated the content of progesterone. Level of an expression of receptors of progesterone and estrogen estimated in endometrium and at EP, also in І a cycle phase. Highlighted are separate clinical and pathogenetic variations of endometrial polyps: isolated polyps, micropolyps, polyps in conjunction with micropolyps. In the course of study, it was found that progesterone deficiency and local immune imbalance with severe hypofunctional NK cells against viral and fungal infestations result in excessive endometrial cell proliferation and development of an isolated polyp. The case of a polyp merging with micropolyps potentiates an active inflammatory process alongside all of the mechanisms mentioned above. Micropolyps as a macroscopic manifestation of an active inflammatory process in chronic endometritis are characterized by focal infiltrates of leukocytes (CD45), macrophages (CD68), plasmacells (CD138) and NK (CD56) cells, whose activity leads to excess abnormal proliferation of endometrium, even in the absence of hormone receptor disorders.

Immune analysis of expression of IL-17 relative ligands and their receptors in bladder cancer: comparison with polyp and cystitis.

BACKGROUND: Bladder cancer, cystitis and bladder polyp are the most common urinary system diseases all over the world. Our former research results show that IL-17A and IL-17 F contribute to the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer (Pca) while IL-17E interacting with IL-17RB might have an anti-tumor effect. RESULTS: Using imunohistochemistry, we systemically compared immunoreactivity of ligands (IL-17A, E and F) and receptors (IL-17RA, IL-17RB and IL-17RC) of IL-17 family, infiltration of inflammatory cells and changes of structural cells (fibroblast cells, smooth muscle and vascular endothelial cells) in sections of bladder tissues from subjects with bladder cancer, cystitis and bladder polyp. Compared with subjects with cystitis, immunoreactivity for IL-17A, IL-17 F and IL-17RC was significantly elevated in the group of bladder cancer (p < 0.01), while immunoreactivity of IL-17E, IL-17RA and IL-17RB, and the infiltrating neutrophils were decreased (p < 0.05). The numbers of infiltrating lymphocytes and phagocytes and CD31+ blood vessels and immunoreactivity of CD90+ fibroblasts were also elevated in patients with bladder cancer compared with those of cystitis. The patterns of IL-17 ligands and receptors, and inflammatory cells and structural cells varied in cystitis, bladder polyp and bladder cancer. In bladder cancer, immunoreactivity of IL-17E and IL-17 F was positively correlated with smooth muscles and lymphocytes, respectively. In addition, immunoreactivity of IL-17A and IL-17E was positively correlated with their receptors IL-17RA and IL-17RB respectively. CONCLUSIONS: The data suggest that changed patterns of expression of the IL-17 cytokine family ligands and receptors might be associated with infiltration of inflammatory cells and structural cells (CD90+ fibroblasts and CD31+ blood vessels), which might also contribute to occurrence and development in bladder cancer.

Th17 expression and IL-17 levels in laryngeal squamous cell carcinoma patients.

CONCLUSION: The Th17 cell frequency in peripheral blood and levels of IL-17 showed significant differences between patients with laryngeal squamous cell carcinoma and those with vocal cords polyps. Serum levels of IL-17 were correlated with laryngocarcinoma staging. OBJECTIVES: To investigate associations among the frequency of Th17 cells, levels of IL-17, and laryngeal squamous cell carcinoma. METHOD: Eighty in-patients with laryngeal squamous cell carcinoma and 114 in-patients with polypus of the vocal cord were enrolled. Th17 cell frequencies in peripheral blood and serum levels of IL-17 were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. The tissue expression levels of IL-17 mRNA transcripts and protein were measured using quantitative RT-PCR or immunohistochemical detection, respectively. RESULTS: Th17 cell frequencies in peripheral blood and serum concentrations of IL-17 were significantly higher in patients with laryngocarcinoma compared with those in patients with polyps (p < 0.01 for both Th17 cells and IL-17 levels). Serum concentrations of IL-17 were significantly higher in patients with advanced laryngocarcinoma than in patients with early laryngocarcinoma (p < 0.01). The mRNA and protein levels of IL-17 were significantly higher in laryngocarcinoma tissues than in adjacent normal tissues (p < 0.01 for mRNA levels, p < 0.05 for protein levels).

Pathologic Features of Colorectal Inflammatory Polyps in Miniature Dachshunds.

The histopathologic characteristics of colorectal inflammatory polyps that formed in Miniature Dachshunds were compared with those of other colorectal proliferative lesions, including adenomas and adenocarcinomas. Fifty-three colorectal polypoid lesions were histopathologically classified into inflammatory polyps (26 cases), adenoma (18 cases), and adenocarcinoma (9 cases). All 26 dogs that were diagnosed with inflammatory polyps were Miniature Dachshunds, indicating that colorectal inflammatory polyps exhibit a marked predilection for this breed. The inflammatory polyps had complex histopathologic features and were classified into 3 stages based on their epithelial composition. In early stage (stage 1), the polyps tended to exhibit a thickened mucosa containing hyperplastic goblet cells, dilated crypts filled with a large amount of mucus, and mild lymphocyte and macrophage infiltration. In later stages (stages 2 and 3), more severe neutrophil infiltration, interstitial mucus accumulation, granulation tissue, and occasional osteoid tissue were seen. Also, a few small foci of dysplastic epithelial cells were detected. The hyperplastic goblet cells, which were a major component of the epithelium of the inflammatory polyps, were positive for cytokeratin 20 (CK20), while the dysplastic epithelial cells found in inflammatory polyps (stage 3) and the tumor cells of the adenomas and adenocarcinomas were negative for CK20. These CK20-negative epithelial cells exhibited cytoplasmic and nuclear immunoreactivity for beta-catenin. In addition, the epithelial cells in the inflammatory polyps demonstrated significantly higher cyclooxygenase 2 and fibroblast growth factor 2 expression than did those of the adenomas and adenocarcinomas, suggesting that the arachidonate cascade is involved in the development of colorectal inflammatory polyps in miniature dachshunds.

[Inflammation, malignancy and immunology in gastrointestinal spindle cell tumors: what is beyond GIST?]. / Entzündung, Malignität und Immunologie gastrointestinaler Spindelzelltumoren : Was gibt es abgesehen von GIST noch?

Many mesenchymal tumors and tumefactions associated with the gastrointestinal tract feature prominent inflammatory cells but the mechanisms for the inflammation and the processes themselves remain poorly understood. Such classic lesions include Kaposi sarcoma, inflammatory fibroid polyp, sclerosing mesenteritis and inflammatory myofibroblastic tumor but, more recently, the recognition of IgG4-related fibrosclerosing disease has resulted in modification of the views on pathogenesis and treatment of such inflammatory lesions in many anatomical sites. In some lesions the inflammation may reflect viral influences (Kaposi sarcoma) or a bacterial infectious trigger (IgG4-related fibrosclerosing disease) whereas in others such an interaction is unclear and alterations in various genes have been detected, such as anaplastic lymphoma receptor tyrosine kinase gene rearrangements in inflammatory myofibroblastic tumor and platelet-derived growth factor receptor alpha (PDGFRA) gene mutations in inflammatory fibroid polyp and some gastrointestinal stromal tumors (GIST). Even the inflammatory milieu of GISTs may have an impact on the outcome. This article discusses the practical diagnostic considerations as well as the theoretical background.

Helicobacter pylori but not gastrin is associated with the development of colonic neoplasms.

Recent studies have suggested that Helicobacter pylori (H. pylori) constitutes a risk for the development of colonic neoplasia. Hypergastrinemia can be induced by H. pylori infection, and gastrin can act as putative promoter of colorectal carcinogenesis. Aim of our study was to assess whether H. pylori infection and/or increased serum gastrin levels are associated with the occurrence of colonic neoplasms. For this, we reviewed prospectively collected data of 377 patients with a minimum age of 50 years who underwent colonoscopy. H. pylori and CagA status were determined by serology. Serum gastrin levels were measured in fasting state by commercially available assay. In H. pylori infected patients (n = 138; 36.6%), the overall prevalence of colonic neoplasms was more frequent compared to H. pylori negative patients (n = 239; 63.4%) (OR = 2.73, 95% CI: 1.76-4.24). H. pylori infection occurred more frequently in patients with hyperplastic polyps (OR = 2.66, 95% CI: 1.23-5.74) and adenomas presenting with low grade intraepithelial neoplasia (IEN) (OR = 1.85, 95% CI: 1.14-2.99). Attributable risk for adenomas with high grade IEN and colorectal adenocarcinoma (n = 14) was not assessed due to the low number of cases. The expression of CagA was also associated with an increased risk for colonic neoplasms (OR = 2.25, 95% CI: 1.29-3.94). Hypergastrinemia did not increase the risk for any colonic neoplasms and there was no difference in basal serum gastrin levels between H. pylori positive and negative patients. In conclusion, H. pylori infection, including CagA expression is associated with an increased risk for the development of colonic neoplasm.

Expression of CD4+ T cell cytokine genes in the colorectal mucosa of inflammatory colorectal polyps in miniature dachshunds.

Inflammatory colorectal polyps (ICRPs) in miniature dachshunds are recently recognized as a major cause of large bowel diarrhea in this dog breed in Japan. ICRPs are characterized by the formation of multiple small polyps and a space-occupying large polyp in the colorectal area, and are thought to be a novel form of inflammatory bowel disease (IBD). In humans, specific cytokine patterns attributed to T helper (Th)1, Th17 and regulatory T cells have important roles in the pathogenesis of IBD. Thus, the aim of the present study was to assess the gene expression of cytokines of T cell subsets in the colorectal mucosa from dogs with ICRPs. Colorectal mucosal specimens from 10 dogs with ICRPs and 14 control dogs were used in this study. Interferon (IFN)-γ, interleukin (IL)-4, IL-17A and IL-10 mRNA expression was assessed using quantitative real-time PCR. IL-17A mRNA expression was significantly increased in large polyps compared to small polyps and controls. IFN-γ and IL-10 mRNA expression in large polyps were significantly higher than in controls. There was no significant difference in IL-4 mRNA expression among the three groups. IL-17A is thought to play important roles in the pathogenesis of ICRPs. IL-10 up-regulation could oppose the proinflammatory function of IL-17A.

Cellular immune environment in endometrial polyps.

STUDY OBJECTIVE: To investigate the immune environment of endometrial polyps (EPs). DESIGN: Prospective case-control study. SETTING: Teaching hospital and university research laboratory. PATIENT(S): Reproductive-age women undergoing hysteroscopy dilation and curettage for benign indications. Samples were collected from women with (n = 23) and without (n = 40) EPs. INTERVENTION(S): Endometrial samples were immunohistochemically stained with antibodies against mast cells (MCs) and regulatory T cells (Tregs). MAIN OUTCOME MEASURE(S): Tryptase+, chymase+, and c-Kit+ MCs and Foxp3+ Tregs were quantified in EPs and polyp-adjacent, polyp-distant, and control endometrium. RESULT(S): Densities of all MC types were highly significantly increased in EPs compared with adjacent, distant, and control endometrium. Chymase+ and c-Kit+ MCs were increased in density in adjacent compared with control endometrium. c-Kit+ MCs were also increased in distant compared with control endometrium. Foxp3+ Treg density was increased in EPs compared with distant and control endometrium and decreased in distant compared with control endometrium. CONCLUSION(S): This study provides novel insights into localized disturbances in the cellular immune environment within EPs consistent with EPs being inflammatory lesions associated with MC overactivity. Tregs are likely to be recruited to EPs in an attempt to suppress the inflammatory process due to the greatly increased presence of MCs. These immunologic disturbances are likely to be involved in the causation of abnormal bleeding and infertility in premenopausal women with EPs, and their role in the pathophysiology requires further research.