OBJECTIVE:Fine-needle aspiration cytology (FNAC) is routinely used in the preoperative evaluation of parotid gland tumors, yet its diagnostic performance varies across categories of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). This study evaluated category-specific malignancy risk and the clinical impact of different diagnostic thresholds. METHODS:We retrospectively analyzed 277 patients who underwent parotidectomy with available preoperative FNAC. Cytologic diagnoses were classified according to the MSRSGC and correlated with final histopathology. Diagnostic performance was assessed using two thresholds: Milan V-VI and Milan III-VI. Trends in malignancy risk across Milan categories were examined, and false-negative and false-positive cases were reviewed by histopathological subtype. Overall discriminatory performance was evaluated using receiver operating characteristic analysis. RESULTS:Final histopathology revealed benign disease in 85.2% and malignancy in 14.8% of cases. Malignancy risk increased significantly across higher Milan categories (p = 0.006). Using Milan V-VI as the threshold yielded high specificity (97.0%) and negative predictive value (88.8%) but low sensitivity (29.3%). Expanding the threshold to Milan III-VI increased sensitivity (78.0%) but markedly reduced specificity (21.2%). Discriminatory performance was poor (AUC 0.622). False-negative results were mainly low-grade malignancies, particularly low-grade mucoepidermoid carcinoma, whereas false-positive results were largely benign oncocytic or hypercellular lesions. CONCLUSIONS:FNAC provides useful preoperative risk stratification for parotid gland tumors within the Milan framework, but its diagnostic value is highly threshold-dependent and limited by tumor biology.

ObjectiveIn pancreatic ductal adenocarcinoma (PDAC), immune and stromal components of the tumor microenvironment critically influence disease progression and survival. Although FoxP3 expression has been linked to prognosis, the clinical relevance of its spatial distribution remains unclear. This study aimed to evaluate the prognostic significance of FoxP3-positive lymphocytes in intratumoral (IT), peritumoral (PT), and tumor-associated stromal (T) compartments.Materials and methodsNinety-eight patients with PDAC who underwent surgical resection between 2015 and 2021 were retrospectively analyzed. FoxP3 expression was assessed immunohistochemically in IT, PT, and T compartments and categorized as low or high based on H-scores. Associations with clinicopathological variables, overall survival (OS), and disease-free survival (DFS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Subgroup analyses were performed according to recurrence status and receipt of adjuvant chemotherapy.ResultsHigh FoxP3 expression in IT, PT, and T compartments was significantly associated with shorter OS. Although FoxP3 expression showed significant associations with DFS in Kaplan-Meier analyses, it did not retain independent significance in multivariate models. Tumor-associated stromal FoxP3 expression correlated with increased stromal response and advanced nodal stage, whereas high PT-FoxP3 expression was associated with positive surgical margins. In patients receiving adjuvant chemotherapy, Kaplan-Meier analyses showed no clear survival separation; however, compartment-specific prognostic effects of FoxP3 were preserved in multivariate analyses.ConclusionFoxP3-positive lymphocyte infiltration represents a clinically relevant prognostic biomarker in PDAC, with its impact on survival strongly dependent on spatial localization within the tumor microenvironment. Compartment-based evaluation of FoxP3 may improve risk stratification and provide a biologically meaningful framework for future immunologically informed therapeutic strategies in PDAC.

Objective:High mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein involved in chromatin remodeling, transcription, DNA replication, and repair. The purpose of this study was to assess the relationship between tissue expression of HMGB1, clinical outcomes, and histopathological characteristics in patients with breast cancer. Materials and Methods:The study included 282 patients with breast cancer. An in vitro diagnostic HMGB1 antibody was applied to the slides of tumor specimens. Results:Overexpression of HMGB1 was found in tumor cells of 123 (43.6%) patients. HMGB1 was only expressed in the nucleus in most tumors (88.7%), while in 32 (11.3%) tumors HMBG1 expression was cytoplasmic and/or extracellular. Severe inflammatory infiltration of the peritumoral stroma was observed in 76 (27%) patients. There was a correlation between remarkable inflammatory cell infiltration in the tumor microenvironment and HMGB1 overexpression, regardless of the molecular subtype, as well as the extranuclear location of HMGB1 expression (p = 0.023). HMGB1 expression was not found to be associated with overall or disease-free survival. However, axillary lymph node metastasis was significantly more common in tumors with intense inflammation (p = 0.024). Conclusion:The proportion of breast cancer patients with HMGB1 expression was lower in the present study than that reported previously. Furthermore, we did not detect a relationship between HMGB1 expression and prognosis. However, the relationship between HMGB1 expression and prognosis had been previously reported only in aggressive breast cancers. It is suggested that understanding the significance of HMGB1 expression in breast cancer may open new treatment opportunities, especially in aggressive and/or triple negative tumors.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality. FoxP3 expression and the tumor microenvironment (TME) play crucial roles in tumor progression and immune evasion. OBJECTIVES: To investigate the association between FoxP3 expression in intratumoral (IT), peritumoral (PT), and tumor-associated (T) regions, and various clinicopathological prognostic factors in PDAC patients. PATIENTS AND METHODS: Ninety-eight PDAC patients diagnosed between 2015 and 2021 were evaluated. FoxP3 expression was assessed by immunohistochemistry in IT, PT, and T regions. Patients were stratified into high and low FoxP3 expression groups based on median values. Correlations with tumor size, stage, histological differentiation, invasion patterns, lymph node metastasis, and survival outcomes were analyzed. Patients were also grouped according to recurrence status (Ex) or survival (Survived) for further clinicopathological evaluation. RESULTS: High FoxP3 expression in IT, PT, and T regions was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). The T-FoxP3 subgroup demonstrated increased stromal response and higher lymph node metastasis incidence. Elevated PT-FoxP3 expression correlated with positive surgical margins in the Ex group. ROC analysis confirmed that high FoxP3 expression correlated with recurrence. Stromal responses were significantly higher in the Ex group and in patients with high FoxP3 expression. Other clinicopathological variables did not differ significantly between groups. CONCLUSION: FoxP3 expression is a promising prognostic biomarker in PDAC, linked to poorer survival outcomes. Targeting FoxP3 may be beneficial in developing future therapeutic strategies to improve patient prognosis.

Background: The survival rate among stomach adenocarcinoma patients is exceedingly low. NGAL (neutrophil gelatinase-associated lipocalin) has pivotal roles in cell proliferation, immunity, and tumorigenesis. KIM-1 (Kidney Injury Molecule-1), also referred to as TIM-1 and HAVcr-1, is a transmembrane glycoprotein located in healthy immune cells and epithelial cells, and its upregulated form is generally found in several human cancers. Aim: The aim of this study was to investigate the prognostic significance of the expression of KIM-1 and NGAL in stomach cancers and identify NGAL-positive inflammatory cells in the tumor microenvironment. Materials and Methods: We immunohistochemically evaluated the expression of NGAL and KIM1 in 172 cases of stomach adenocarcinomas. Result: The mean age of the patients was 64.07 ± 12.35 years, and the mean and median follow-up period were 25.5 and 20.3 months, respectively. The expression rates of KIM-1 and NGAL in tumor cells were identical at 31.4% (n = 54). In 27 of these cases, both proteins were present. Among the deceased patients, the rate of simultaneous KIM-1 and NGAL positivity was relatively higher (p = 0.041). NGAL-positive inflammatory cells were observed in 13.4% of cases, with no significant correlation between these cells and survival times (p = 0.497). However, there was a negative correlation between survival times and KIM-1 (p = 0.037) and NGAL (p = 0.016) expressions in tumor cells. Conclusions: The present study has shown that KIM-1- and NGAL-positive tumor cells are influential in gastric tumorigenesis. Given the progress in anti-KIM-1 therapy, the presence of KIM-1 expression could contribute to the development of new treatment options for aggressive gastric cancer. However, these discoveries need to be validated in larger-scale studies.

Background: Even the slightest bit of evidencehave demonstrated that elevated expressions of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) play critical roles in tumor progression in many malignant diseases. But still a little is known about their effects on ovarian carcinogenesis. In this retrospective study, we havetargeted to investigate the positivity of KIM-1 and NGAL (if any) in a spectrum of ovarian surface epithelial neoplasms. Methods: Herein we have assessed the prognostic values of KIM-1 and NGAL tissue expressions and their relations with some clinicopathologic parameters of 128 cases with ovarian neoplasms. Results: This study group consists of cases of 34 (26.6%) benign, and 10 (7.8%) borderline serous tumors, 29 (22.7%) serous, 38 (29.7%) endometrioid and 17 (13.3%) mucinous carcinomas. KIM-1 expression was found in both tumor and inflammatory cells, but NGAL expression was detected only in inflammatory cells. Although it is known that KIM-1 biomarker is expressed at a higher rate in carcinoma cases compared to benign tumors, due to the limited number of cases any statistically significant intergroup difference could not be observed (p = 0.217). Besides, NGAL-positive inflammatory cells were detected at a statistically significantly higher rate in cases with borderline serous tumors and carcinomas (p = 0.003). Conclusions: Herein we have shown the presence of a correlation between infiltrationof NGAL-positive inflammatory cells and malignant behavior of ovarian neoplasms. In addition, we have detected the strong cytoplasmic expression of KIM-1 (or its synonym T-cell immunoglobulin and mucin domain/TIM-1), in more than one-third of the malignant ovarian neoplasms which provides supportive evidence favoringthe use of anti-TIM1 immunotherapies in the treatment of patients with KIM-1 positive ovarian neoplasms.

BACKGROUND/AIMS:Neuroendocrine cell hyperplasia is a non-neoplastic proliferation of enterochromaffin-like cells and is considered a premalignant lesion because of their potential to progress to neuroendocrine tumor. In this study, we aimed to evaluate the demographic and clinical features, laboratory, radiological and endoscopic findings, gastric biopsy histopathological features, follow-up frequency, and histopathological findings of patients diagnosed with gastric neuroendocrine cell hyperplasia as well as to investigate the factors that play a role in the development of neuroendocrine tumors on the basis of neuroendocrine cell hyperplasia.MATERIALS AND METHODS:The study has been conducted in 2 centers with 282 patients that were grouped as those with and without neuroendocrine tumor. Individuals with control endoscopy were separated as those with regression of neuroendocrine cell hyperplasia and those without regression, and the determined parameters were evaluated between the groups.RESULTS:The most common histological subtype of neuroendocrine cell hyperplasia was linear+micronodular (50.4%). Neuroendocrine tumor developed in 4.3% (12/282) of the patients with neuroendocrine cell hyperplasia after a mean of 36 months. The presence of polyps as confirmed via endoscopy and dysplasia as confirmed via histopathological examination was significantly higher in favor of the group with neuroendocrine tumor (P = .01). In patients with neuroendocrine cell hyperplasia regressed and patients in whom it did not regress were examined, the rate of asymptomatic patients and increased sedimentation rate were found in favor of the group that did not regress (P = .02 and P = .02), but no difference was found in other parameters.CONCLUSION:Neuroendocrine tumor development rate was found to be 4.3% in the background of neuroendocrine cell hyperplasia. Two factors predicting progression from neuroendocrine cell hyperplasia to neuroendocrine tumor can be elaborated as the presence of polypoid appearance due to neuroendocrine cell hyperplasia as confirmed via endoscopy and dysplasia as confirmed via histopathological examination.

Introduction: Pancreatic ductal (PDACs), and ampullary (AACs) adenocarcinomas have different clinical and pathological prognostic features. The aim of our study is to comparatively evaluate the characteristic clinicopathologic features, prognostic factors and overall survival of resectable PDACs and AACs. Methods: We retrospectively compared a total of 120 patients with resectable adenocarcinomas stemming from main pancreatic duct, ampulla of Vater, and both regions in terms of prognostic clinicopathologic features and mean survival rates. Results: Adenocarcinomas (AC) originating from pancreatic ducts (n: 75) ,ampulla of Vater (n:19), and both of these anatomical (n:26) regions were pancreatobiliary (PB) (93.3%), intestinal (5.1%), and mixed ( 1.6%) histologic type tumors. There was no statistically significant difference between the tumor groups in terms of lymphovascular invasion (LVI) (p = 0.225), but perineural invasion (PNI) was seen at a statistically significantly lower rate in cases with AAC (p = 0.002). Lymph node involvement was seen more frequently in PDACs. A statistically significant intergroup difference was found when Pearson's chi-square test was used (p = 0.065). The median survival time was longer in AAC and stage I cases compared to those with PDAC and stage II-IV disease. Conclucion: In our study, tumor stage, perineural invasion and lymph node involvement were evaluated as important prognostic parameters in pancreatic and ampullary adenocarcinomas. A statistically significant difference was not detected between tumor groups regarding mean survival rates. Adenocarcinomas originating from the pancreatic head outside the ampullary region and also from the ampulla had independently poor prognostic factors closely comparable to PDACs.

Introduction: Information regarding HER2-low tumors in metastatic gastric cancer is sparse. Our aim here was to determine the frequency of low HER2 expression in metastatic gastric cancer and to compare the clinicopathological characteristics, survival, and treatment response of HER2-low patients with HER2-zero patients. Methods: The clinicopathological features, treatment responses, and survival of HER2-low tumors and HER2-zero tumors were compared. Results: Of 226 patients, 71 (31.4%) had low HER2 expression and 155 (68.6%) had zero HER2 expression. HER2-low tumors were detected more frequently in older patients and in low-grade tumors than HER2-zero tumors (69% vs. 47.7%, p = 0.003, 16.9% vs. 3.8%, p < 0.001). On the contrary, HER2-zero tumors were more likely to be poor grade than HER2-low tumors (47% vs. 22.2%, p < 0.001). All patients received a first-line chemotherapy regimen. The disease control rate was not statistically different between both groups (40% vs. 46.4%, p = 0.11). The median survival was 12.05 (95% CI, 8.09–16.02) months in HER2-low patients and 10.41 (95% CI, 8.52–12.3) months in HER2-zero patients with no statistical difference (p = 0.73). Conclusion: HER2-low metastatic gastric cancer has a higher rate of being low grade than HER2-zero tumors. HER2-low metastatic gastric cancer is similar to HER2 zero in terms of chemotherapy response and survival.

Background: Trastuzumab is commonly utilized in the management of metastatic HER2-positive breast cancer. Our main goal was to examine the clinical outcomes and immune markers of patients who received trastuzumab and chemotherapy treatment. Methods: Between 1995 and 2012, a total of 98 patients diagnosed with metastatic HER2-positive breast cancer were retrospectively analyzed at Ege University Hospital and Tepecik Training and Research Hospital. The clinicopathological characteristics and clinical outcomes of the patients were assessed, and the associations between response rates, survival and the immune profiles of tumor infiltrating lymphocytes were statistically evaluated. Results: The average age of patients at the time of diagnosis was 50.1 +/- 10.3 (ranging from 30 to 79) years. The mean follow-up period for all patients was 97.9 +/- 53.8 months. Among the patients, complete response was observed in 24.5%, partial response in 61.2%, and stable disease in 8.2% of cases. The average progression-free survival was 50.3 +/- 26.9 months (ranging from 1 to 163 months), and the average overall survival was 88.8 +/- 59.4 months (ranging from 12 to 272 months). After analyzing all cases, it was found that patients who were younger (p=0.006), exhibited higher CD3-positivity (p=0.041), presented with higher FOXP3-positivity (p=0.025), showed complete or at least partial response to treatment (p=0.008), and experienced a long-term response to trastuzumab (and chemotherapy) treatment had longer survival (p=0.001). Conclusion: Patients with HER2-positive breast cancer, who initially respond positively to palliative trastuzumab and chemotherapy treatment, can achieve long-term tumor remission lasting for several years.

Abstract Purpose Trastuzumab is commonly utilized in the management of metastatic breast cancer. Our main goal was to examine the extended outcomes of patients experiencing a persistent positive response to trastuzumab treatment. Methods Between 1995 and 2012, a total of 98 patients diagnosed with inoperable, locally recurring or metastatic HER2-positive breast cancer were retrospectively analyzed at Ege University Hospital and Tepecik Training and Research Hospital. The clinical and pathological characteristics of the patients were assessed, and the associations between response rates, survival, and the immune profiles of tumor infiltrating lymphocytes were statistically evaluated. Results The average age of patients at the time of diagnosis was 50.1 ± 10.3 (ranging from 30 to 79) years. The mean follow-up period for all patients was 97.9 ± 53.8 months. Among the patients, complete response was observed in 24.5%, partial response in 61.2%, and stable disease in 8.2% of cases. The average progression-free survival was 50.3 ± 26.9 months (ranging from 1 to 163 months), and the average overall survival was 88.8 ± 59.4 months (ranging from 12 to 272 months). After analyzing all cases, it was found that patients who were younger (p = 0.006), exhibited higher CD3- positivity (p = 0.041), presented with higher FOXP3- positivity (p = 0.025), showed complete or at least partial response to treatment (p = 0.008), and experienced a prolonged response to trastuzumab treatment (p = 0.001) had longer survival. Conclusions Patients with HER2-positive breast cancer, who initially respond positively to palliative trastuzumab treatment, can achieve long-term tumor remission lasting for several years.

The coexistence of Hirschsprung’s disease (HD) with anorectal malformation (ARM) is rare but many surgeons still ask pathologists to look for ganglia in the terminal rectum or fistula. In this study, we aimed to highlight the rarity of this association and question the necessity of histological evaluation. After obtaining board review approval, rectal specimens of ARM patients who underwent corrective surgery in the last 8 years were re-analyzed by two blinded pathologists for the presence and structure of ganglia. Clinical and radiological data of patients retrieved from center records and correlated with histopathologic findings. 67 patients with ARM were identified, distal rectal specimen was obtained in 47. The median age at the time of surgery was 11 months (2 days–59 months). A normal pattern of ganglia was present in 51.1

Objective To investigate the diagnostic accuracy of the Thyroid Imaging, Reporting and Data System of the American College of Radiology in thyroid nodules. Material and Method A total of 151 nodules were collected from 62 patients undergoing thyroid surgery in our center between August 2017 and September 2018. Ultrasonographic features of each nodule were recorded and classified according to the Thyroid, Imaging Reporting and Data System of the American College of Radiology by two radiologists and compared with a one-to-one basis on histopathology. Results The median size of 151 thyroid nodules measured on the ultrasound and in the pathology specimens were 19 (3-85) mm and 17 (0-97) mm, respectively. Papillary carcinoma was demonstrated in 28 patients (45%), papillary microcarcinoma in 14 patients (22.5%), and Hurthle cell carcinoma in 1 (1.6%) patient. Overall sensitivity, specificity, positive predictive value, and negative predictive value for this nodule risk stratification model were analyzed as 82.5%, 57%, 64.58%, and 77.67%, respectively. Conclusion Setting a definitive size threshold for fine needle aspiration might be misleading, instead signifying the malignant features on ultrasonography, and making a decision for surgery on an individual base should be recommended.

BACKGROUND:Considerable progress has been made in the treatment of multiple myeloma (MM) patients with the development of various new agents that increased survival rates over the past fifteen years. Cereblon (CRBN) plays an important role in mediating the antitumor effects of immunomodulatory drugs (IMiDs) among these new agents. The aim of our study is to investigate immunohistochemically (IHC) cereblon protein expression status in MM.METHODS:Immunohistochemically, CRBN expression and its relationship with various prognostic factors were evaluated in bone marrow biopsies of 96 patients with MM in a single centre.RESULTS:Cytoplasmic and nuclear CRBN expression was detected in all neoplastic cells. While a complete or partial response to treatment was obtained in 45 patients, the disease was stable in 13 and progressive in 17 patients. Survival was longer in those treated with IMiD-containing regimens (p = 0.044). Both the survival rate (p = 0.013) and the survival time were significantly increased (p = 0.023) in those who received the treatment protocol containing protease inhibitors. A significant relationship was found between the treatment protocol and treatment response in the chi-squared analysis (p = 0.008). Although the longest survival time - though not statistically significant - was detected in the group treated with protease inhibitors (log rank, p = 0.217). The survival analysis revealed the presence of a relationship between IgG and IgA positivity and survival.CONCLUSIONS:In this study, the survival time of the patients who received treatment regimens containing protease inhibitors and IMiD was longer, independent of the presence of strong nuclear CRBN expression. The survival rate was significantly higher in those who used IMiD and protease inhibitors in combination. Since the survival rate was found to be increased in IgG positive cases and we thought that evaluation of immunoglobulin tissue expression in MM cases can provide prognostic prediction.

Objective:Breast cancer is the most common cancer among women worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) has important roles in immunity, cell proliferation, and carcinogenesis. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein also known as hepatitis A virus cellular receptor 1 and T-cell immunoglobulin and mucin, has restricted expression in immune cells and healthy epithelial cells, but it is up-regulated in several human cancers. The aim of this study was to determine the prognostic values of NGAL and KIM-1 expression in tumor cells and to detect the presence of NGAL-positive neutrophils (PNL) in the tumor microenvironment.Materials and Methods:The expression of NGAL and KIM-1 protein were assessed by immunohistochemical staining in tissue specimens from 412 primary breast cancer cases.Results:In this series, the mean age of the patients was 55.6±12.4 years. In 218 (52.9%) cases, there was NGAL expression in tumor cells. In 104 (25.2%) cases there was KIM-1 expression in tumor cells. NGAL-positive inflammatory cells were seen in tumors of 45 (10.9%) cases. There was no significant relationship between NGAL-positive PNL presence in the tumor microenvironment and other clinicopathological features. However, there was a significant association between the presence of in situ carcinomas and NGAL expression (p = 0.008) and KIM-1 expression (p = 0.020) in tumor cells.Conclusion:This study has demonstrated positivity of NGAL and KIM-1 in breast cancer cells. Considering the development of anti-KIM-1 therapies, the presence of KIM-1 expression may be a new treatment option in breast cancer, especially in in situ component-rich tumors. These findings should be confirmed in larger series.

Objective: MicroRNAs represent an emerging class of small non-coding RNAs that play important roles in the post-transcriptional regulation of gene expression. This study was aimed to evaluate the relevance of microRNA in classical mixed cellularity Hodgkin lymphoma (MCHL) pathogenesis. Methods: The expressions of 157 microRNAs in lymph nodes from 20 paediatric and 20 adult patients with MCHL and 20 normal lymph nodes (controls) were analysed. Results: The patients' mean age was 7.4 years for the children and 47.4 years for the adults. Most of the patients were male (n = 14, 70%) in both groups. Stage III disease (n = 9, 45%) was common in the paediatric group, while stage II disease (n = 18, 90%) in others. Thirty-six cases (90%) were alive, while four (10%) were deceased. With microRNA sequencing, it was determined that miR-1273e, miR-4322, miR-5008-5p, and miR-6511b-5p were upregulated, while miR-508-5p was down-regulated in only paediatric tumours. Conclusion: These results suggest that microRNAs may play an important role in the biology of paediatric MCHL and may be useful in developing therapies targeting microRNAs.

Although novel therapies have improved the treatment outcome of patients, chronic lymphocytic leukaemia (CLL) is still considered incurable. Recently, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), causing coronavirus disease 2019 (Covid 19), emerged in late 2019, and it has posed a global health threat. In a limited number of cases, it has been shown that some lymphoma types spontaneously regress after SARS-CoV2 infection suggesting that the infection can trigger de immune system against the tumour cell. Cross-reactivity of pathogen-specific T cells with tumour antigens and natural killer cell activation can be the possible mechanism of this hypothesis.

BACKGROUND:The accumulation of excess glutamate in the synapse leads to excitotoxicity, which is the underlying reason of neuronal death in intracranial tumors.METHODS AND RESULTS:We identified the expression levels of glutamate dehydrogenase, glutamine synthetase and sirtuin 4 in U87 cell line and various intracranial tumors. mRNA expressions of glutamate dehydrogenase (GDH), glutamine synthetase (GS) and sirtuin 4 (SIRT4) were analyzed in various intracranial tumors using qPCR. GDH, GS and SIRT4 protein expressions were analyzed in glioblastoma (U87) and glial (IHA-immortalized human astrocytes) cell lines via western blotting. The protein expressions of SIRT4 and GS were shown to be elevated and GDH protein expression was reduced in U87 cells in comparison to IHA cells. All types of intracranial tumors displayed lower GS mRNA expressions compared to controls. SIRT4 mRNA expressions were also shown to be lower in all the tumors and grades, although not significantly. GDH mRNA expression was found to be similar in all groups.CONCLUSION:The molecular mechanisms of glutamate metabolism and excitotoxicity should be discovered to develop therapies against intracranial tumors.