The frequency and prognostic role of P53 and P16 immunoexpression in primary ovarian mucinous tumors.

BACKGROUND: Primary ovarian mucinous tumors are uncommon. Factors leading to invasive progression and metastatic disease have not been fully delineated yet. The aim of this study is to determine the rates of p53 and p16 immunoexpressions in primary ovarian mucinous tumors, to investigate their relationship with clinicopathologic factors and their impact on prognosis and survival. METHODS: Seventy-eight primary ovarian mucinous tumors (30 mucinous cystadenomas, 30 mucinous borderline tumors (MBOT), 18 mucinous carcinomas (MOC)) were evaluated immunohistochemically with p53 and p16 staining. The demographic, clinicopathological data, and postoperative follow-up findings of the patients were analyzed. RESULTS: Mutation-type p53 staining was present in 1/30 (3.3 %) cystadenoma, 10/30 (33.3 %) MBOT and 9/18 (50 %) MOC (p = 0.001). p16 overexpression was detected in 3/30 (10.0 %) MBOT and 5/18 (27.8 %) MOC, but not in any cystadenoma (p = 0.04). The frequency of mutation-type p53 staining in MBOTs with microinvasion was higher (71.4 %) than in those without (28.6 %, p = 0.026). The frequencies of p16 or p53 mutations were similar in MBOTs with and without intraepithelial carcinoma, or mural nodule (p > 0.05). In MOCs with ovarian surface involvement, mutation-type p53 staining was detected in 66.7 % (6/9) and p16 overexpression in 55.6 % (5/9) of the cases. A significant difference was found between MOCs with or without ovarian surface involvement regarding the frequency of p16 overexpression (p = 0.029). Any relationship was not detected between survival and p53 and p16 expression in MOCs (p > 0.05). CONCLUSION: p53 and p16 mutation rates were higher in MOCs compared to mucinous cystadenomas and MBOTs and suggest a relevant role in the development of primary ovarian mucinous carcinoma, however further studies are needed in this regard.

The protective effect of boric acid on cholestatic rat liver ischemia reperfusion injury.

BACKGROUND: To evaluate the potential protective effects of boric acid (BA) in experimental cholestatic liver ischemia reperfusion (IR) injury model. METHODS: The study included 24 female rats which were divided into 3 groups each containing 8 rats. The control group (Group 1) only received laparotomy. In the IR group (Group 2) biliary tract ligation was applied and 1 week later 45 min ischemia and 1 h reperfusion with relaparotomy without any treatment was implemented. In the treatment BA+IR group (Group 3). 1 week after the biliary ligation intraperitoneal administration of 200 mg/kg BA was given 10 min before the ischemia for 45 min and reperfusion for 1 h with relaparotomy. Liver tissue and blood samples were taken for histopathological and biochemical examination. Ischemia modified albumin (IMA), SCUBE1, total antioxidant status (TAS), and total oxidant status (TOS) levels were also examined. RESULTS: Compared to control, groups IR and BA+IR had higher serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total, and direct bilirubin levels. Albumin value was high in the control group and low in the other groups. In terms of IMA levels there was no significant difference between groups (p > 0.05). When SCUBE-1 levels were examined groups IR and BA+IR were significantly higher than the group 1. TAS was highest in the group BA+IR whereas TOS was highest in the group IR and lower in the group BA+IR. In histopathological analysis, loss of intercellular border loss in hepatocytes, diffuse nuclear pycnosis and mild to moderate neutrophilic cell infiltration were observed in the IR group. Statistically significant dissociation, hemorrhage and severe neutrophilic cell infiltration were seen in hepatocytes of rats with IR (p < 0.05). DISCUSSION: BA has promising results in the treatment of experimental IR injury of the cholestatic liver because of its antioxidant effects. It may be used in clinical practice after more extensive studies about the effects of BA on IR injury of the cholestatic liver.

The value of 18FDG PET/CT parameters, hematological parameters and tumor markers in predicting KRAS oncogene mutation in colorectal cancer.

OBJECTIVE: In this study we investigated the predictive value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), neutrophils/lymphocytes ratio (NLR), platelets/lymphocytes ratio (PLR), carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in the prediction of KRAS gene mutation which plays an important role in the choice of treatment in colorectal cancer patients. SUBJECTS AND METHODS: A total of 55 cases with untreated colorectal cancer who had undergone both PET/CT examinations for initial staging and also mutation analysis of KRAS oncogene were studied. Fluorine-18-FDG PET/CT parameters (SUVmax, MTV, TLG), hematological parameters (NLR, PLR), and tumor markers (CEA, CA 19-9) were recorded and the relationship between these parameters and KRAS oncogene mutation was evaluated using receiver operating characteristics (ROC) analysis and multiple logistic regression analysis. RESULTS: In 20 cases mutations in the KRAS gene were detected, while in 35 cases mutations were not observed (wild-type). ROC analysis revealed that SUVmax, MTV, TLG, NLR, PLR, and CA 19-9 could not predict mutations in KRAS oncogene (P=0.600, 0.263, 0.214, 0.057, 0.104, 0.189, respectively) although CEA value showed signi..cant difference (P=0.031) but without high value of the area under the curve (0.676). Multivariate logistic regression analysis also did not show significant association between KRAS gene mutations and SUVmax, MTV, TLG, NLR, PLR, CEA, CA 19-9 values. CONCLUSION: We observed that in patients with colorectal cancers, we cannot predict KRAS gene mutations using PET/CT parameters (SUVmax, MTV, TLG), hematological parameters (NLR, PLR) or tumor marker CA 19-9. We detected a significant but not very strong association only between CEA and KRAS mutations.

Stanniocalcin-2 expression in glioblastoma - A novel prognostic biomarker: An observational study.

The objective of this study was to assess the prognostic relevance of Stanniocalcin-2 (STC2) expression, as determined via immunohistochemistry in tumor tissue, in a cohort of 83 patients diagnosed with glioblastoma who underwent maximal safe surgical resection followed by radiotherapy concurrent with adjuvant temozolomide. STC2 expression levels were categorized using a 3-tiered semiquantitative system: negative expression (level 0-), low expression (level 1+), and high expression (levels 2 + and 3+). Patients were categorized into 2 distinct groups according to their STC2 expression levels: negative STC2 (-/+) and positive STC2 (++/+++). The primary outcome measure was the relationship between STC2 expression and progression-free survival (PFS), with overall survival (OS) serving as the secondary endpoint. Kaplan-Meier survival analysis confirmed that patients exhibiting high STC2 expression had significantly shorter OS (8 vs 20 months, P < .001) and PFS (6 vs 18 months, P < .001) than those with low or negative STC2 expression. Multivariate analysis revealed that STC2 expression was an independent prognostic factor for both OS (hazard ratio: 0.4; 95% confidence interval: 0.2-0.8; P < .05) and PFS (hazard ratio: 0.3; 95% confidence interval: 0.2-0.4; P < .05) in patients with glioblastoma. Furthermore, elevated STC2 expression in GBM was correlated with several established aggressive clinicopathological characteristics, including advanced age (≥65 years), low ECOG PS (≥2), and isocitrate dehydrogenase mutation negativity. These findings underscore that heightened STC2 expression within the tumor tissue of GBM patients functions as an adverse prognostic marker, correlating with an elevated risk of progression and reduced OS. Therapeutic interventions targeting the AKT-mTOR, ERK1-2, and mitogen-activated protein kinase pathways as well as immune checkpoint inhibitors and vascular endothelial growth factor blockade, as well as potential forthcoming antibody-drug conjugates targeting the STC2 molecule, have the potential to broaden the scope of combined treatment strategies.

Effect of ischemia-reperfusion injury on elafin levels in rat liver.

BACKGROUND: The aim of this study was to quantify serum levels of elafin, a serine protease inhibitor, and to assess its effects on histopathological and biochemical parameters in hepatic ischemia-reperfusion injury. METHODS: Forty female Wistar albino rats were divided into five groups: Group 1 served as the control group. Liver ischemia was induced for 30 minutes in the other four groups. An additional 1-hour, 2-hour, and 3-hour reperfusion was induced in Groups 3, 4, and 5, respectively. At the end of the experiment, intracardiac blood samples were obtained for biochemical examination, and tissue samples from the liver were taken for histopathological examination. Levels of elafin, ischemia-modified albumin (IMA), total antioxi-dant status (TAS), and total oxidant status (TOS) were also examined. RESULTS: Serum elafin levels decreased beginning from Group 2, with the lowest level reached in Group 5 (p<0.01). The IMA level was the lowest in the control group and the highest in Group 5 (p<0.01). TOS, aspartate aminotransferase (AST), and alanine amino-transferase (ALT) levels were lowest in the control group and highest in Group 5 (p<0.01). Group 5 had the highest IMA/albumin ratio, although no significant differences were found between these four groups. The lowest TAS level was found in the control group, but a stable and significant increase was not detected in the other groups. No significant differences were found between the groups in terms of alkaline phosphatase (ALP) and albumin levels. A negative correlation was observed between serum elafin levels and AST, ALT, and TOS levels (p<0.01). The number of Grade 1 histopathological results was found to be higher in the groups with reperfusion (Groups 3, 4, 5). In histopathological subgroup analysis, while the elafin level was lower in Grade 1 group, AST, ALT, and TOS levels were higher (p<0.01). Additionally, the IMA/albumin ratio was found to be higher in the Grade 1 group (p=0.02). CONCLUSION: In hepatic ischemia-reperfusion injury, elafin levels decreased as the reperfusion time increased. As the reperfusion time increased, both hepatocyte damage and oxidant capacity increased, with a negative correlation observed between these findings and elafin levels. Therefore, elafin may play a protective role in hepatic ischemia-reperfusion injury and could assist clinicians in assessing liver injury.

FOXA1 is associated with high tumor grade, myometrial invasion and lymph node invasion in endometrial endometrioid carcinoma.

OBJECTIVES: FOXA1 expression has been demonstrated in several hormone-dependent cancers. However, data are limited concerning the role of FOXA1 in endometrial cancers. The present study aimed to investigate FOXA1 expression via the microarray technique in benign hyperplasia, endometrial intraepithelial neoplasia, and endometrial endometrioid carcinoma. We also aimed to determine whether there were any associations between FOXA1 expression, tumor grade, myometrial invasion and lymphatic invasion. MATERIAL AND METHODS: Paraffin-embedded sections prepared from samples obtained from 114 patients who underwent surgical hysterectomy or curettage were analyzed. Data were retrieved from digitally-stored medical records. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded tissue blocks. Full tumor sections were used for immunohistochemical analysis performed. RESULTS: Carcinomas with nuclear grade 3 had higher FOXA1 values than others, while grade 2 carcinomas also had higher FOXA1 values relative to grade 1 (p < 0.001). FOXA1 values of FIGO stage III carcinomas were significantly higher than others and stage II values were also significantly higher than stage I FOXA1 values (p < 0.001). Patients with myometrial and lymph node invasion had significantly higher FOXA1 values than others (p < 0.001 and p = 0.047, respectively). FOXA1 had 91.30% sensitivity, 63.60% specificity and 77.78% accuracy for predicting the presence of myometrial invasion with a cut-off value of 9. CONCLUSIONS: FOXA1 expression is higher in endometrial endometrioid carcinoma compared to benign endometrial hyperplasia or intraepithelial neoplasia. In patients with endometrial endometrioid carcinoma, high FOXA1 expression is associated with high tumor grade, myometrial and lymph node invasion. However, FOXA1 expression is not associated with lymphovascular or cervical invasion.

The extent of cyclin D1 expression in endometrial pathologies and relevance of cyclin D1 with the clinicopathological features of endometrioid endometrial carcinoma.

BACKGROUND: Cyclin D1, a member of the cyclin protein family, is instrumental in the cell cycle due to its influence on the progression from G1 to the S phase. Its overexpression causes reduced doubling time and is also associated with clonogenic growth. The purpose of the present study was to assess cyclin D1 expression in patients with simple hyperplasia (SH), endometrial intraepithelial neoplasia (EIN) and endometrioid endometrial carcinoma, and to evaluate whether there was an association between cyclin D1 expression and the clinicopathological features of endometrioid endometrial carcinoma. METHODS: Retrospective data were available for 193 patients (30 SH, 40 EIN, and 123 endometrioid endometrial carcinoma cases). To detect cyclin D1 expression, immunohistochemistry staining was performed with tissue microarrays. RESULTS: The percentage of cases with positive cyclin D1 staining were 30%, 60% and 78%, for SH, EIN and endometrioid endometrial carcinoma, respectively (P < 0.001). Carcinomas with higher nuclear grade, histological grade, and FIGO grade displayed higher mean cyclin D1 expression compared to lower grade carcinomas. In addition, patients with lymphovascular invasion (P = 0.006), myometrial invasion (P < 0.001) and lymph node invasion (P < 0.001) had higher mean cyclin D1 expression compared to those without invasion. There was a significant correlation between cyclin D1 expression and clinicopathological features of endometrioid endometrial carcinoma including tumor grade, FIGO grade, lymphovascular invasion, lymph node invasion and myometrial invasion (P < 0.05 for each). CONCLUSION: Cyclin D1 expression is significantly higher in patients with endometrioid endometrial carcinoma compared to that of the SH and EIN. The extent of cyclin D1 expression is strongly correlated with nuclear and histological grade, myometrial invasion, lymphovascular invasion and lymph node invasion in patients with endometrioid endometrial carcinoma. These findings contribute in several ways to our understanding of cyclin D1 expression and provide a basis for future research on this topic.

Two Uncommon Sites of Metastasis: Breast and Hypophysis Metastases of Head and Neck Adenoid Cystic Carcinoma Detected by FDG PET/CT.

Adenoid cystic carcinoma (ACC) is a rare epithelial malignancy arising from secretory glands, particularly the salivary glands. It tends to invade nerves and has a high potential for distant hematogenous metastasis, especially to the lungs, bone, liver and brain. The breast and hypophysis are not common sites of ACC metastatic disease. Herein, we report a case of ACC of the head and neck region with two unusual sites of metastases, the hypophysis and breast.

TTF-1 may not be a reliable marker for differentiating metastasis from brain tumors.

OBJECTIVE: TTF-1 is widely used as an immunohistochemical marker of lung and thyroid tumors. However, TTF-1 expression has been described in tumors from other sites. The presence of TTF-1 expression in primary brain tumors is largely unclear and has not been clearly specified yet. We characterized expression of two TTF-1 clones in primary brain tumors with relevance to tumor types and grades. MATERIAL AND METHOD: We studied immunohistochemistry with tissue micro-array, using both clones (8G7G3/1 and SPT24) in 45 primary brain tumors of different types and grades. Our cases consisted of 1 grade I, 7 grade II, 4 grade III, 20 grade IV astrocytic tumors; 9 meningiomas, 2 oligodendrogliomas, 1 schwannoma and 1 medulloblastoma. RESULTS: We have found TTF-1 nuclear staining using the SPT24 clone in 4 cases (3 cases were grade IV and 1 was grade III). Focal and weak staining was seen in three cases and moderate-strong and diffuse staining was seen in one case. All the tumors were negative with clone 8G7G3/1. Clone SPT24 was more sensitive but less specific. CONCLUSION: TTF-1 can also be expressed in primary brain tumors, particularly grade III to IV tumors. TTF-1 expression was a rare finding in previous studies, however strong and diffuse staining was not observed until today. We think that TTF-1 nuclear expression in high-grade astrocytic tumors cannot rule out primaries even when diffuse and strong staining. Clinical and pathological parameters should be evaluated together.

First Aid Knowledge of University Students in Poisoning Cases.

OBJECTIVES: Poisoning is a crucial public health problem which needs serious approach and response to treatment. In case of poisoning, proper first aid is lifesaving and application should be applied in every condition. This research was conducted in order to evaluate first aid knowledge of university students for poisoning. METHODS: The research was conducted between the dates of May 2013-June 2013 with the permission gained from the University Rectorship. The cohort of the research contained 4,560 students who received education in Istanbul. The sample of the study included 936 students who accepted to participate in the research and attended the school during the research. The data were collected by using a questionnaire form, which had 21 questions prepared by researchers. Analysis of the data was carried out with a percentage evaluation method and chi square tests in a computer environment. RESULTS: In our study, 92.6% of students (n=867) knew the phone number of the ambulance in case of emergency. In addition, 57.3% of students (n=536) knew the phone number of the poison hotline, and it was seen that they answered correctly the questions regarding the relation between body system and indications of poisoning. It was determined that the students who received education in medical departments answered the questions correctly more than the students who had education in other departments. (p≤0.001, p≤0.01). CONCLUSIONS: It was observed that the university students in medical departments had more first aid knowledge on poisoning cases compared to the students in other departments who did not have sufficient information regarding these issues. It is thought that first aid education in all departments of universities, both poisoning and other first aid issues, should be conveyed to all students.

Voltage-gated sodium channel activity promotes prostate cancer metastasis in vivo.

Epigenetic upregulation of voltage-gated sodium channels (VGSCs) has been reported in a number of carcinoma cell lines and tissues. Furthermore, a large body of experimental evidence suggested that functional VGSC expression enhances various in vitro cell behaviours, such as directional motility, that would be involved in the metastatic cascade. However, it is not known if VGSC activity promotes metastasis in vivo. Here, using the Copenhagen rat model of prostate cancer and blocking VGSC activity in primary tumours with tetrodotoxin, we show (1) that the number of lung metastasis is reduced by >40% and (2) that lifespan is significantly improved.