Nicotinamide N-methyltransferase overexpression may be associated with poor prognosis in ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer-related mortality in women. Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme and there is growing evidence to suggest that it plays an important role in cancer progression. This is the first study to examine the expression of NNMT in serous ovarian cystadenomas, serous borderline tumours, low grade serous carcinomas (LGSC) and high grade serous carcinomas (HGSC) and investigate the potential independent association of NNMT expression with survival. Tissue samples were analysed immunohistochemically for NNMT expression. The stromal NNMT score was significantly higher in HGSC compared to serous cystadenomas and serous borderline tumours (p < .001, p < .043, respectively). The mean stromal NNMT score of patients with HGSC was significantly higher than patients with LGSC (p = .043). Patients with low expression of NNMT had a significantly higher mean recurrence-free survival than patients with high expression (p = .036). NNMT may support tumour progression in ovarian cancer by promoting desmoplastic stromal tumour reaction. NNMT overexpression may be associated with poor prognosis and can be a therapeutic target in ovarian cancer.IMPACT STATEMENTWhat is already known on this subject? Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that is overexpressed in many malignancies. Its overexpression was shown to lead to histone hypomethylation, which in turn can decrease and increase the expression of tumour suppressor proteins and onco-proteins, respectively. NNMT was also shown to play a role in epithelial-to-mesenchymal transition, which is critical in tumour progression and the stromal tumour reaction. The stromal tumour reaction was recently targeted with promising therapeutic results in ovarian cancer.What do the results of this study add? The expression of NNMT in various ovarian neoplasms including serous cystadenomas, borderline tumours and serous carcinomas has not been studied and independently associated with poor survival, previously. This study suggests that NNMT is progressively overexpressed in the stroma of ovarian neoplasms from benign cysts to HGSCs. NNMT overexpression appears to be independently associated with poor survival in ovarian cancer.What are the implications of these findings for clinical practice and/or further research? The implications of these findings are that NNMT may play an important role in the stromal tumour reaction, and therefore its overexpression may contribute to poor survival. NNMT overexpression may be an important target of ovarian cancer therapy.

Expression and Clinical Significance of Nicotinamide N-Methyltransferase in Cervical Squamous Cell Carcinoma.

Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme, overexpressed in various human malignancies. It is associated with cancer progression and resistance to treatment. The role of NNMT in cervical cancer has not been studied thus far. We aimed to evaluate expression of NNMT in cervical squamous cell carcinoma (SCC) and investigate its clinical significance. NNMT expression was assayed by use of immunohistochemistry in 61 cases of SCC, 11 cases of high-grade squamous intraepithelial lesion, 17 cases of low-grade squamous intraepithelial lesion, and 51 benign cervical tissues. NNMT immunoreactivity was scored based on staining intensity and percentage of positively stained cells. The expression of NNMT was significantly higher in SCC than in benign tissue, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion (P<0.001). NNMT expression in benign tissue was significantly lower than in low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. When stratified according to stage, NNMT expression was significantly higher in patients with stage III and IV than those in stage I and II disease (P=0.009). For all stages, patients with metastatic pelvic or para-aortic lymph nodes had significantly higher NNMT expression than patients without nodal involvement (P=0.001). Although preliminary, this is the first study to detect overexpression of NNMT in SCC and increased expression associated with advanced stage and metastatic lymph nodes. NNMT should be investigated further in cervical cancer as a potential therapeutic target and a prognostic indicator.

Nicotinamide N-methyltransferase expression and its association with phospho-Akt, p53 expression, and survival in high-grade endometrial cancer

Background/aim: Nicotinamide N-methyltransferase (NNMT) is an enzyme that is overexpressed in malignancies. NNMT expression has not been previously studied in endometrial cancer (EC). Increased phospho-Akt (pAkt) levels in response to NNMT overexpression have been reported in in vitro studies of different cancer types. We assayed NNMT expression in primary and metastatic high-grade EC and investigated the relationship of NNMT with p53, pAkt, and survival. Materials and methods: NNMT, pAkt, and p53 expressions were assayed in 100 tissue samples of benign endometria, primary EC, and metastatic EC by immunohistochemistry. Results: The NNMT immunoreactivity score was significantly higher in primary high-grade EC than benign endometrial tissue (P = 0.001). NNMT expression in metastatic tissue was significantly higher than in primary cancer (P < 0.001). Metastatic stromal NNMT expression was significantly higher than that of the adjacent tumor and stroma adjacent to the primary tumor. p53 expression in the primary tumor showed a significant positive correlation with omental NNMT and pAkt expression. NNMT expression was also correlated with pAkt expression in metastatic tissue. NNMT overexpression in metastatic tissue was associated with decreased survival (P = 0.039). Conclusion: This study suggests that NNMT may promote cancer progression and that NNMT overexpression is associated with aberrant p53 expression, pAkt, and poor survival. NNMT's role in cancer progression could make it a target of EC therapy.

Effects of Prednisolone, L-Asparaginase, Gemfibrozil, and Combinations of These Elements on Mice Lipid Profile, Liver, and Pancreas.

The aim of this study is to determine the effects of L-asparaginase (L-ASP), corticosteroids (CSs), and antilipidemics, separately and in combination, on the lipid profiles and the liver and pancreas histology in mice. This study included 8 groups of 7 mice each. Before any drug administration, serum samples were taken from all of the mice. Then, normal saline was applied to the control group, and a medication or combination of medications was applied to the other groups. Levels of triglycerides, cholesterol (COL), and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were determined, and the livers and pancreases were evaluated histologically at the end of the study. Triglycerides increased significantly in the CS-only and the L-ASP-only groups, COL increased significantly in the CS-only group, and HDL increased significantly in the CS-only and the antilipidemic-only groups. LDL was significantly lower in the CS-only and the L-ASP-only groups. CSs and L-ASP were significantly effective in liver necrosis, L-ASP was significantly effective in liver balloon degeneration, and CS were significantly effective in pancreas vacuolization. Triglyceride measurement is recommended before/during CS and/or L-ASP treatment. Starting with an antilipidemic agent can be considered to avoid possible complications in patients with significantly high rates. Indicators of a possible liver or pancreas injury should also be considered.

The evaluation of reliability and contribution of frozen section pathology to staging endometrioid adenocarcinomas.

PURPOSE: To evaluate the reliability and accuracy of intraoperative pathological findings, compared to permanent section (PS) and to understand contributions of frozen section (FS) to final staging in patients with endometrioid carcinomas. METHODS: This is a retrospective analysis of 79 patients undergoing intraoperative FS and with endometrioid adenocarcinomas. Intraoperative pathological findings were compared with final results as to grade, depth of myometrial invasion (MI), cervical involvement, lymphovascular space invasion (LVSI) and stage. We also analyzed whether staging procedures like pelvic or para-aortic lymph node metastasis, peritoneal cytology and extension beyond of uterus were related to FS findings. Staging was based on the FIGO 2009. RESULTS: FS results were agreement in 89.9 % for grade, 88.6 % for depth of MI, 100 % for cervical invasion, and 92.4 % for LVSI, compared with PS. On FS, 12, 16.6 and 44.4 % of specimens in stages of IA, IB and II became upstaged in final pathology, respectively. Of 79 cases, 5 (6.3 %) were upstaged to IIIC1, and 3 (3.8 %) were upstaged to IIIC2 because of lymph node metastasis. A significant relationship was detected between lymph node metastasis, and FS grades (p = 0.001), LVSI (p = 0.000), cervical invasion (p = 0.006) and MI (p = 0.001). CONCLUSION: We consider that intraoperative FS is a useful procedure to identify poor prognostic pathological factors. While grading, depth of MI, cervical stromal invasion and LVSI on FS are significant in predicting lymph node metastasis, the existence of cervical stromal invasion and LVSI should be considered more effective parameters in the identification of metastatic endometrial cancer risks.

Inframammarial Giant Fibroadenoma Removing and a Nipple-sparing Breast Reconstruction in an Adolescent: A Case Report.

Fibroadenomas are common, benign breast tumors that usually affect women in the second and third decade of life. Giant fibroadenomas often cause significant concern for the patient or family regarding malignant potential and altered breast development. Most fibroadenomas are benign. Local excision of small lesions through a circumareolar or inframammary incision rather than radical surgery is appropriate. Breast ultrasound represents the most commonly used imaging modality for the study of pediatric female breast masses and fibroadenomas. Detailed descriptions of the sonographic appearances of fibroadenomas in young girls are sparse. We believe that surgical treatment for the patient should include tumor extirpation and immediate restoration of breast appearance, minimizing visible scars, protection of the developing breast bud, nipple, and areola. This modality reduces psychosocial comorbidity.

Synovial sarcoma in a premature newborn.

Synovial sarcoma is rarely detected in infants, with an annual incidence of 0.5 per million. Synovial sarcoma occurs more frequently in adolescents and young adults, with the majority of patients presenting between 15 and 40 years of age. It is extremely rare, however, in pediatric patients under 2 years of age. In the present study we examined a 3-day-old male infant born at 32 weeks who had a mass on his left arm. Synovial sarcoma was identified on histopathological and immunohistochemical analysis of biopsy material acquired from the mass. On whole body magnetic resonance imaging, diffuse metastases were detected in the bilateral lungs in the retroperitoneal zone, in bilateral suprarenal glands, the right liver lobe, the right kidney, and the brain. To our knowledge this is the youngest patient to be diagnosed with synovial sarcoma in the literature.

The effect of platelet-rich plasma on osteochondral defects treated with mosaicplasty.

PURPOSE: This study investigated the efficacy of platelet-rich plasma (PRP) on articular surfaces on which the mosaicplasty technique was performed. Our hypothesis was that PRP can accelerate the osseointegration process and enhance the quality of articular integrity after the mosaicplasty procedure. METHODS: Standard defects were created in the femoral groove of both patellofemoral joints of 12 New Zealand rabbits. PRP solution was placed inside the defect before fixation of the osteochondral autografts and injected inside the involved joint after capsular closure of the tested knees. The contralateral knees served as the control sides. The animals were euthanized three or six weeks after mosaicplasty, and both limbs were assessed according to Pineda's histological grading scale. Significance level was set at p ≤ 0.05 a priori, and the Mann-Whitney U test was used for statistical analysis. RESULTS: Histologic findings at the interface between the transferred autograft and the original cartilage revealed better integration of the adjacent surfaces in the mosaicplasty with PRP group three weeks after the procedure; the difference was significant (p < 0.05). However, no significant difference in the transition zone was observed between the groups six weeks after the experiment (p = 0.59). CONCLUSIONS: Our animal model showed that adjunctive use of PRP produced a better healing response and resulted in superior histological scores after three weeks compared with the mosaicplasty-only procedure. Interpretation of our results is important in terms of rapid return to previous activity levels. Thus, application of PRP can represent a valid therapeutic option for improving the efficacy of mosaicplasty by stimulating the local healing response.

A Rare Tumor Causing Optic and Oculomotor Nerve Compression: Clivus Plasmacytoma Case Report.

Plasmacytomas rarely affect the skull base and may be found as an isolated lesion or as a part of multiple myeloma. The typical feature of plasmacytomas is aggressive bone destruction in the skull. It is often confused with the chordoma of the clivus. The most common location for skull-base plasmacytomas is the nasopharynx. The most commonly affected cranial nerve in clivus tumors is the abducens nerve. In our 64-year-old male case, a plasmacytoma was detected in the clivus. There was ptosis and decreased vision due to optic nerve and oculomotor nerve involvement due to the plasmacytoma. Radiotherapy was applied for the treatment.

The Use of Platelet-Rich Fibrin and Polypropylene Mesh in Repair of Nasal Septal Perforation.

OBJECTIVE: In this study, we aimed to investigate the effectiveness of the use of polypropylene mesh and platelet-rich fibrin (PRF) in nasal septal perforation (NSP) repair. STUDY DESIGN: Prospective experimental study. SETTING: Laboratory. METHODS: Twenty-four adult male New Zealand rabbits were used in our study. In all subjects, a 10 × 10 mm perforation was created in the septum. The subjects were divided into 3 equal groups according to the different methods used in perforation closure. The bilateral mucosal flap was used in the control group, polypropylene mesh + bilateral mucosal flap in the mesh group, and polypropylene mesh + bilateral mucosal flap + PRF in the mesh + PRF group. RESULTS: NSP treatment success rate was found to be significantly higher in the mesh (4/6, 66.7%) and mesh + PRF (6/6, 100%) groups compared to the control group (0/6, 0%). Re-epithelialization score was higher in the mesh + PRF group and the control group compared to the mesh group. While the necrosis, neutrophil, and abscess scores were highest in the mesh group, they were similar to the control group in the mesh + PRF group. CONCLUSIONS: While polypropylene mesh significantly increases the success rate in NSP repair, it causes severe inflammatory responses. However, when polypropylene mesh is combined with PRF, it both increases the rate of perforation closure and significantly reduces the complications associated with the use of mesh.

Association of endocan expression with clinicopathological prognostic parameters in breast carcinoma.

BACKGROUND: Breast cancer (BC) is a common malignancy in women. Some molecules, including endocan, are still under investigation as potential prognostic factors in BC. OBJECTIVE: In the present study, we aimed to determine the relationship between endocan expression and clinicopathological prognostic parameters in BC. METHODS: Two hundred and fifty-five patients diagnosed with BC were included in the present study. The immuno-reactivity scoring (IRS) system was used to reveal the tissue endocan expression levels. RESULTS: We found that endocan expression is associated with tumor necrosis, tumor size, and the presence of lobular carcinoma in situ (LCIS) in BC. There was no relationship between endocan expression and survival as well as other clinicopathological prognostic parameters. CONCLUSION: Endocan overexpression in BC is associated with some prognostic parameters, including tumor necrosis, tumor size, and the presence of LCIS. Further studies with larger series are needed to reveal the clinical and therapeutic implications of endocan in BC.

Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.

BACKGROUND: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples. MATERIALS AND METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n = 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants. RESULTS: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs - ERBB2, FGFR1, and AR copy number gains and 5 SNVs - IDH1.R132H, TP53.E204∗, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively. CONCLUSION: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeqTM. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.

New defining body (Ugras body) in polypoid dedifferentiated liposarcoma of the vallecula. Histomorphological, immunohistochemical and molecular genetic findings.

This is a description of a dedifferentiated liposarcoma seen in a 27-year-old female patient. The tumor originated from the vallecula and contains distinctive bodies. These bodies, which are formed by the aggregation of tumor cells, contain collagen in several regions and are oval or elongated in shape. Immunohistochemically, the tumor cells showed staining for MDM2, p16, Vimentin, beta catenin, smooth muscle actin, bcl-2 and p53. Ki-67 ratio was 17% in hypercellular areas of the tumor. Molecular genetic studies have found copy number increase for CDK4 and MDM2 genes. Final histopathological diagnosis was dedifferentiated liposarcoma with unique bodies. Although meningothelial-like whorls is defined in dedifferentiated liposarcoma, this body has not been defined until now. To our knowledge, this is the first case of a DDL containing a cellular spindle cell component seen as rare sheet-like areas and distinctive ball-like, or elongated, serpiginous formations in the middle of paucicellular, collagenous areas.

Capsule endoscopy findings in celiac disease.

Capsule endoscopy (CE) is a noninvasive imaging method used to evaluate intestinal mucosa. We aimed to examine intestinal mucosal changes in celiac disease (CD) with CE. Eight untreated patients who had anti-endomysial antibody-positive duodenal biopsy results consistent with CD were included in the study. Villous atrophy, scalloping, fissuring, and mosaic pattern (consistent with CD) were detected in seven patients; one patient was excluded for early meal consumption. No patchy involvement was found in the intestine or distal region of the intestine (ileum) in any of the patients. The common feature of all patients was that villous atrophy, scalloping, fissuring, and mosaic patterns detected in the proximal intestine gradually decreased towards the distal intestine. CE provided no diagnostic contribution to CD when compared with duodenal biopsy. It can be used to show villous atrophy in selected cases and to evaluate the extension of intestinal involvement in CD.

The effects of microwave emitted by cellular phones on ovarian follicles in rats.

OBJECTIVE: The aim of this study was to investigate whether there were any toxic effects of microwaves of cellular phones on ovaries in rats. METHODS: In this study, 82 female pups of rats, aged 21 days (43 in the study group and 39 in the control group) were used. Pregnant rats in the study group were exposed to mobile phones that were placed beneath the polypropylene cages during the whole period of pregnancy. The cage was free from all kinds of materials, which could affect electromagnetic fields. A mobile phone in a standby position for 11 h and 45 min was turned on to speech position for 15 min every 12 h and the battery was charged continuously. On the 21st day after the delivery, the female rat pups were killed and the right ovaries were removed. The volumes of the ovaries were measured and the number of follicles in every tenth section was counted. RESULTS: The analysis revealed that in the study group, the number of follicles was lower than that in the control group. The decreased number of follicles in pups exposed to mobile phone microwaves suggest that intrauterine exposure has toxic effects on ovaries. CONCLUSION: We suggest that the microwaves of mobile phones might decrease the number of follicles in rats by several known and, no doubt, countless unknown mechanisms.

[Treatment of olfactory neuroblastoma via subfrontal and midfacial degloving approaches: a case report]. / Olfaktör nöroblastomun subfrontal kraniofasyal ve midfasyal degloving yaklasimlarla tedavisi: Olgu sunumu.

A 12-year-old girl presented with complaints of nasal obstruction and a right infraorbital swelling. A biopsy obtained from the right nasal passage revealed olfactory neuroblastoma. The tumor was completely excised via subfrontal craniofacial and midfacial degloving approaches. No recurrence was observed during a three-year follow-up.

Prognostic factors and COX-2 expression in advanced stage esophageal squamous cell carcinoma.

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including squamous cell carcinomas of the esophagus, but its clinicopathologic role in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to analyze expression of COX-2 in ESCC and to correlate this expression with clinicopathologic parameters and survival. From 1999 to 2003, endoscopic tissue samples from 110 patients with ESCC were collected for analysis. COX-2 expression was examined through immunohistochemical staining. Clinicopathologic data were analyzed to verify significance. COX-2 expression was detected in 50 of 110 ESCC specimens (45%). COX-2 expression was negative to weak in 73% (COX-2 low) and moderate to strong in 27% (COX-2 high) of tumors. Statistical differences between COX-2 high and COX-2 low were found according to status of the stage (stage IVM1a/IVM1b) (P=.001): cancer antigen (CA) 19-9 (normal/high) (P%.011), CA 12-5 (normal/high) (P=.011), and CA 15-3 (normal/high) (P=.035). Survival was significantly reduced among patients with high COX-2 expression (median overall survival, 3 mo) when compared with the COX-2 low group (median overall survival, 6 mo) (P=.0001). In the univariate analysis, age, body mass index, stage, COX-2, lactate dehydrogenase, CA 12-5, and CA 15-3 were significant factors for survival. With the use of COX regression analysis, only stage (P=.000), COX-2 (P=.000), lactate dehydrogenase (P=.023), and CA 15-3 (P=.002) were independent prognostic factors. Results showed that in patients with ESCC, COX-2 overexpression was significantly correlated with visceral metastases IVM1b). COX-2 overexpression is an unfavorable prognostic factor in ESCC.

Possible role of Helicobacter pylori in the etiopathogenesis of chronic otitis media.

OBJECTIVE: To investigate a possible contribution from Helicobacter pylori to the etiopathogenesis of chronic otitis media. STUDY DESIGN: Prospective clinical trial. METHODS: Tympanomastoidectomy, radical mastoidectomy, and modified radical mastoidectomy procedures were performed according to the pathology of ear disease. Biopsy specimens were taken from middle ear, mastoid antrum, and tympanic orifice of eustachian tube. Helicobacter pylori DNA was extracted from these biopsy specimens by using nested polymerase chain reaction. RESULTS: Helicobacter pylori DNA was detected in 3 (7.9%) of 38 chronic otitis media patients. CONCLUSION: Even though it is possible to detect Helicobacter pylori in middle ear cleft in chronic otitis media, its role in the etiopathogenesis of the issue is controversial.

Melanotic neuroectodermal tumor in a newborn.

Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon, fast-growing, pigmented neoplasm of neural crest origin; it primarily affects the maxilla of the infants during the first year of life. Approximately 200 instances of this tumor are reported in the medical literature. We present a case of newborn with MNTI on the left maxillary alveolar ridge. The patient underwent complete surgical resection without maxillectomy. There has been no recurrence in a follow-up period of 1 year. The diagnostic features and management alternatives of MNTI are discussed.