Grading Of Tumors Research Articles

Grading and proliferation assessment of diffuse astrocytic tumors with monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging and diffusion kurtosis imaging

PurposeTo compare the main parameters derived from monoexponential, biexponential and stretched-exponential diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) with respect to diagnostic performance for tumor grading and proliferation assessment in diffuse astrocytic tumors (DATs). Materials and methodsFifty-eight pathologically confirmed DAT patients who underwent DWI and DKI on a 3-T scanner were prospectively collected and retrospectively reviewed. Measurements including the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), distributed diffusion coefficient (DDC), heterogeneity index (α), mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) were compared between tumor grades (Ⅱ, Ⅲ, and Ⅳ) by using a Jonckheere-Terpstra test. Receiver operating characteristic (ROC) curves were used to assess the diagnostic efficacy of these parameters. Spearman’s rho with the Ki-67 labeling index (LI) was calculated for each parameter. ResultsMK values differed significantly between all DAT subtypes and increased with grade. The ADC, D, f, DDC, α and MD values were significantly higher in grade Ⅱ tumors than in grade Ⅲ/Ⅳ tumors. D* values were significantly lower in grade Ⅱ tumors than in grade Ⅳ tumors (all P < 0.05). In discriminating between grade Ⅱ and Ⅲ tumors, α, MK, MD, D and f had significantly greater area under the ROC curve (AUC) values than D* and FA (0.927, 0.901, 0.896, 0.895, and 0.889, respectively vs 0.659 and 0.598, respectively, P < 0.05). In discriminating between grade Ⅲ and Ⅳ tumors, only MK demonstrated acceptable discrimination (AUC = 0.711). MK and D showed a strong correlation with the Ki-67 LI (ρ = 0.791 and -0.789, respectively, P < 0.001). D*, f, MD, ADC, DDC and α showed a moderate correlation (|ρ| ranged from 0.415 to 0.698, P < 0.05). ConclusionMK and D have considerable potential to predict the degree of proliferation of DATs. MK could effectively characterize microstructural changes throughout the malignant transformation of DATs and provided useful complementary information for grading.

Magnetic Resonance Imaging-Based Grading of Cartilaginous Bone Tumors: Added Value of Quantitative Texture Analysis.

The aim of this study was to assess the interreader agreement and diagnostic accuracy of morphologic magnetic resonance imaging (MRI) analysis and quantitative MRI-based texture analysis (TA) for grading of cartilaginous bone tumors. This retrospective study was approved by our local ethics committee. Magnetic resonance imaging scans of 116 cartilaginous bone neoplasms were included (53 chondromas, 26 low-grade chondrosarcomas, 37 high-grade chondrosarcomas). Two musculoskeletal radiologists blinded to patient data separately analyzed 14 morphologic MRI features consisting of tumor and peritumoral characteristics. In addition, 2 different musculoskeletal radiologists separately performed TA including 19 quantitative TA parameters in a similar fashion. Interreader reliability, univariate, multivariate, and receiver operating characteristics analyses were performed for MRI and TA parameters separately and for combined models to determine independent predictors and diagnostic accuracy for grading of cartilaginous neoplasms. P values of 0.05 and less were considered statistically significant. Between both readers, MRI and TA features showed a mean kappa value of 0.49 (range, 0.08-0.82) and a mean intraclass correlation coefficient of 0.79 (range, 0.43-0.99), respectively. Independent morphological MRI predictors for grading of cartilaginous neoplasms were bone marrow edema, soft tissue mass, maximum tumor extent, and active periostitis, whereas TA predictors consisted of short-run high gray-level emphasis, skewness, and gray-level and run-length nonuniformity. Diagnostic accuracies for differentiation of benign from malignant as well as for benign from low-grade cartilaginous lesions were 87.0% and 77.4% using MRI predictors exclusively, 89.8% and 89.5% using TA predictors exclusively, and 92.9% and 91.2% using a combined model of MRI and TA predictors, respectively. For differentiation of low-grade from high-grade chondrosarcoma, no statistically significant independent TA predictors existed, whereas a model containing MRI predictors exclusively had a diagnostic accuracy of 84.8%. Texture analysis improves diagnostic accuracy for differentiation of benign and malignant as well as for benign and low-grade cartilaginous lesions when compared with morphologic MRI analysis.

An evidence-based approach to assess the accuracy of intravoxel incoherent motion imaging for the grading of brain tumors.

Background:Differentiation of high-grade gliomas (HGGs) and low-grade gliomas (LGGs) is an important clinical problem because treatment strategies vary greatly. This study was performed to investigate the potential diagnostic value of incoherent intravoxel motion imaging (IVIM) to distinguish HGG from LGG by meta-analysis.Methods:A computerized search of the literature was performed using the free-access PubMed database, Web of Science, and Chinese biomedical database, and relevant articles until September 18, 2018 that used IVIM to distinguish HGG from LGG were included. All analyses were performed using Review Manager 5.3 and Stata. Mean difference (MD) at 95% confidence interval (CI) of the apparent diffusion coefficient (ADC), diffusion coefficient value (D), perfusion fraction value (f), and perfusion coefficient value (D∗) were summarized.Results:Nine studies were used for general data pooling. In the tumor parenchyma (TP) regions, subgroup analysis revealed D∗ in HGG is higher than in LGG (MD = 1.19, P = .002), and D in HGG is lower than in LGG (MD = −1.06, P = .001). However, no significant difference in f (MD = 0.89, P = .056) was detected between HGG and LGG. In the white matter regions, HGG had higher D∗ (MD = 0.76, P = .04) compared with LGG, while no marked differences between the D value (P = .07) and f (P = .09) values.Conclusion:The present meta-analysis shows that the ADC, D, and D∗ values derived from IVIM may be useful in differentiating HGG from LGG. Considering the small sample of this study, we need to be cautious when interpreting the results of this study. Other prospective and large-sample randomized controlled trials were needed to establish the value of IVIM in differentiating HGG from LGG.

Advances in the management of upper tract urothelial carcinoma: improved endoscopic management through better diagnostics.

As a rare disease, the management of upper tract urothelial carcinoma (UTUC) continues to evolve. While radical nephroureterectomy remains the gold standard, there is a growing desire to pursue nephron-sparing approaches through endoscopic management, particularly for low-risk disease or in the setting of imperative indications. A particular challenge for those undertaking endoscopic management is appropriate grading and staging of tumors, and thereby appropriate patient selection. In this review we will cover the current state of diagnostics for UTUC as well as highlight the challenges in accurate diagnosis. Additionally, we will focus on emerging technologies to aid in optimizing diagnostic accuracy in UTUC. This will include discussion of narrow band imaging, photodynamic diagnosis, optical coherence tomography, and confocal laser endomicroscopy.

Assessment of tumour-associated necrosis provides prognostic information additional to World Health Organization/International Society of Urological Pathology grading for clear cell renal cell carcinoma.

The aims of this study were to evaluate the impact of tumour-associated necrosis (TAN) on metastasis-free survival for clear cell renal cell carcinoma (RCC), and to determine whether TAN provides survival information additional to World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading. The study consisted of 376 cases of clear cell RCC treated by nephrectomy, for which follow-up was available. WHO/ISUP grade was assigned, and sections were assessed for the presence of TAN. American Joint Committee on Cancer (AJCC) pT staging category and tumour size were also recorded. The development of metastatic disease was taken as the clinical endpoint, and survival analyses, utilising univariate and multivariate models, were performed. WHO/ISUP grades were: grade 1, 35 cases (9.3%); grade 2, 188 cases (50.0%); grade 3, 91 cases (24.2%); and grade 4, 62 cases (16.5%). Staging categories were pT1-pT2 [234 tumours (62.2%)] and pT3-pT4 [139 tumours (37.0%)]. TAN was seen in 128 cases (34.0%). Neither TAN nor metastases were seen in grade 1 tumours. Among grade 2-4 tumours, those with TAN had a significantly worse prognosis than those without TAN (P=0.017, P=0.04, and P=0.006, respectively). Multivariate analysis (WHO/ISUP grade, pT staging category, and TAN) showed all three variables to be independently associated with outcome (P=0.009, P=0.005, and P=0.001, respectively). For all tumour grades and pT staging categories, it was found that the presence of TAN was associated with a 2.91-fold greater risk of metastatic disease. Tumour-associated necrosis is an important prognostic factor for clear cell RCC, independently of WHO/ISUP grade. This supports the suggestion that TAN could be incorporated into tumour grading criteria.

Phosphorylated Histone H3 (PHH3) as a Novel Cell Proliferation Marker and Prognosticator for Meningeal Tumors: A Short Review.

Cell proliferation markers are used in grading of brain tumors and in patient stratification for different treatments. Therefore, defining simple and accurate proliferation markers are of essential importance. Ki67 labeling index is widely studied, yet it is subject to interlaboratory variability. Ki67 protein is expressed on all cell cycle phases except G0 and does not precisely reflect proliferating cells. Counting mitotic figures (MFs) is used in World Health Organization grading of brain tumors (meningiomas), but the detection of MFs on conventional hematoxylin and eosin stained slides is very time consuming. Further, karyorrhexis and pyknosis in apoptotic or crushed cells may mimic mitotic morphology and falsify counting results. Histone H3 phosphorylation on serine-10 is specific to mitosis and phosphorylated histone H3 (PHH3) proliferation markers (as counts defined per area or as indices defined per cell numbers) are increasingly being used to evaluate proliferation in various tumors. Herein, we review current data on PHH3 proliferation markers in meningeal tumors. PHH3-staining highlights mitotic cells and makes easier of rapid grading by driving pathologist's attention on the most mitotically active areas. Thereby, it would function more sensitive in detecting MFs that might be otherwise overloked and more precise by reducing interobserver variability through allowing the pathologist to analyze if the stained nuclei exhibit morphologic features of mitosis.

Profilin-1 deficiency leads to SMAD3 upregulation and impaired 3D outgrowth of breast cancer cells

BackgroundAdhesion-mediated activation of FAK/ERK signalling pathway, enabled by the formation of filopodial protrusions (FLP), has been shown to be an important event for triggering of dormancy-to-proliferation switch and metastatic outgrowth of breast cancer cells (BCC). We studied the role of actin-binding protein profilin1 (Pfn1) in these processes.MethodsQuantitative immunohistochemistry (IHC) of BC tissue microarray (TMA) and survival analyses of curated transcriptome datasets of BC patients were performed to examine Pfn1’s association with certain clinicopathological features. FLP formation and single cell outgrowth of BCC were assessed using a 3D matrigel culture that accurately predicts dormant vs metastatic outgrowth phenotypes of BCC in certain microenvironment. Gene expression studies were performed to identify potential biological pathways that are perturbed under Pfn1-depleted condition.ResultsLower Pfn1 expression is correlated with lower nuclear grade of breast tumours and longer relapse-free survival of BC patients. Pfn1 depletion leads to defects in FLP and outgrowth of BCC but without impairing either FAK or ERK activation. Guided by transcriptome analyses, we further showed that Pfn1 depletion is associated with prominent SMAD3 upregulation. Although knockdown and overexpression experiments revealed that SMAD3 has an inhibitory effect on the outgrowth of breast cancer cells, SMAD3 knockdown alone was not sufficient to enhance the outgrowth potential of Pfn1-depleted BCC suggesting that other proliferation-regulatory pathways in conjunction with SMAD3 upregulation may underlie the outgrowth-deficient phenotype of BCC cells upon depletion of Pfn1.ConclusionOverall, these data suggest that Pfn1 may be a novel biomarker for BC recurrence and a possible target to reduce metastatic outgrowth of BCC.

Axillary ultrasound-guided core biopsy in breast cancer: identifying higher nodal burden and more aggressive clinicopathological characteristics.

Patients with sentinel lymph node (SLN) metastases may not require axillary lymph node dissection (ALND) but it remains unclear if patients with a positive ultrasound-guided axillary core biopsy (ACB) would satisfy such criteria. The aim of this study was to assess if breast cancer patients with a positive pre-operative ACB have more aggressive tumour characteristics/higher axillary nodal burden compared to those with a positive SLN. Data was extracted from a prospectively maintained breast cancer database between 2012 and 2015. Patients who underwent ALND after either positive ACB or SLN were included and tumour characteristics/nodal burden were compared. One hundred eighty patients underwent ALND, 125/180 after positive ACB and 55/180 after positive SLNB. Patients with positive ACB were more likely to undergo mastectomy (chi-square test; p = 0.03) and have higher tumour grades (Mann-Whitney test; p < 0.01) compared to the SLNB group. Median positive nodes excised during ALND were 2 (1-22) and 1 (1-11) for ACB and SLNB groups respectively (p < 0.001). Fifty-six patients received neoadjuvant chemotherapy (NCT). Of 72/125 patients in the ACB group not receiving NCT, the median number of positive nodes was 4 (range, 1-22). Ten patients within the ACB group satisfied ACOSOG Z011 criteria. Breast cancer patients with a positive ACB are more likely to have aggressive tumour characteristics and higher nodal burden compared to those identified as having axillary nodal disease on SLNB, which may affect surgical decision making.

Correlation of epidermal growth factor receptor score with prognostic variables in transitional cell carcinoma of urinary bladder among north-eastern Indian population

Background: Epidermal growth factor receptor (EGFR) has demonstrated over expression in bladder tumours and correlation with stage and grade of tumours. The aim of present study was to find the relation between score of the EGFR in Transitional Cell Carcinoma (TCC) of bladder and its various prognostic variables.Methods: This is a retrospective study conducted in Dept of Urology, Gauhati Medical College Hospital between Dec 2016 and July 2017. Forty cases of TCC bladder that were operated either by TURBT or radical cystectomy have been taken. However, patients with CKD, pre-existing systemic disease and UTI were excluded from the study. Presence of EGFR and its score were analysed. The rating was done as 0 (non-immunoreactive), 1+ (weak), 2+ (moderate) and 3+ (strong). The correlation between EGFR score and the various factors like age, sex, stage, size of tumour, presence of CIS, tumour grade, muscle invasion, number of tumours and type of stalk were evaluated statistically using chi square tests.Results: Average age is 59.825 years and male to female ratio is 5.6:1. EGFR score is not significantly related with age, sex, stage of disease, muscle invasiveness or number of tumours whereas size of tumour, presence of CIS changes, grade of TCC and type of tumour stalk bears statistically significant relation with EGFR score.Conclusions: Studies have shown EGFR positivity to be associated with high tumour stage, tumour progression, and poor clinical outcome. Authors have found size &gt;3cm, CIS changes, high grade tumours and broad-based stalks to be significantly associated with higher EGFR scores among patients with TCC of bladder.

WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies

PurposePathological parameters assessed on biopsies and resection specimens have a pivotal role in the diagnosis, prognosis and management of patients with renal cell carcinoma (RCC).MethodsA non-systematic literature search was performed, updated to January 2018, to identify key standards and controversies in the pathological classification, grading and staging of RCC.ResultsAlthough most RCCs exhibit characteristic morphology that enables easy categorisation, RCCs show considerable morphological heterogeneity and it is not uncommon for there to be difficulty in assigning a tumour type, especially with rarer tumour subtypes. The differentiation between benign and malignant oncocytic tumours remains a particular challenge. The development of additional immunohistochemical and molecular tests is needed to facilitate tumour typing, because of the prognostic and therapeutic implications, and to enable more reliable identification of poorly differentiated metastatic tumours as being of renal origin. Any new tests need to be applicable to small biopsy samples, to overcome the heterogeneity of renal tumours. There is also a need to facilitate identification of tumour types that have genetic implications, to allow referral and management at specialist centres. Digital pathology has a potential role in such referral practice.ConclusionMuch has been done to standardise pathological assessment of renal cell carcinomas in recent years, but there still remain areas of difficulty in classification and grading of these heterogeneous tumours.

Expression of the Hippo signalling effectors YAP and TAZ in canine mammary gland hyperplasia and malignant transformation of mammary tumours.

Canine mammary tumours (CMTs) are common neoplasms in dogs that feature many of the clinical, genetic and molecular characteristics of human breast cancer. Despite their high metastatic potential, few adjuvant chemotherapeutic treatment options exist for malignant CMTs, and the development of novel, targeted pharmacological approaches will require a better understanding of their pathogenesis. As recent evidence suggests that dysregulated Hippo signalling is involved in the development and progression of breast cancer, we sought to determine if this pathway could also play a role in CMT. The expression of the Hippo signalling effectors YAP and TAZ was analysed by immunoblotting and immunohistochemistry in samples including normal mammary gland, lobular hyperplasia, benign tumours and malignant tumours of all grades. We found a significant increase in TAZ (but not YAP) expression occurred in lobular hyperplasia relative to normal mammary gland, suggesting a role for TAZ in non-neoplastic epithelial proliferation. Nuclear expression of both TAZ and YAP were significantly higher in malignant tumours than in benign ones, suggesting that Hippo dysregulation could play a role in CMT malignant transformation. No differences in YAP or TAZ expression were detected between grades of malignant tumours. Together, our results indicate that alterations in Hippo signalling may play a role in the pathogenesis of CMT, in a manner similar to breast cancer. Hippo pathway components may therefore represent targets for the development of novel chemotherapeutic agents that could be useful for the treatment of both the human and canine diseases.

I004] Diffusion-weighted MRI: Techniques, applications and challenges in oncology

Diffusion-Weighted MRI (DWI) is a powerful method that exploits Brownian motion of water molecules to explore tissue microstructure. It is made possible through the dependence of the MRI signal from diffusing spins on the direction and strength of applied magnetic field gradients. The signal loss increases with the apparent diffusion constant, and the direction dependency arises through the presence of barriers in the tissue that hinders or restricts the diffusion process. By repeating the measurement with several different gradient directions and strengths, anisotropic diffusion in tissue can be characterized. Several analysis methods, both model-free and based on biophysical diffusion models are available to characterize tissue microstructure, although most available protocols have been developed to characterize white matter fibers in the brain. There is an increasing interest to use DWI in oncology and its use is multi-faceted. For pre-surgical planning of brain tumor resections it can be used to identify essential white matter fibers that should be spared. However its use is not limited to the brain or to the characterization of surrounding tissue. Any soft matter tissue can greatly benefit from this technique, and especially a detailed characterization of tumor tissue can be achieved. For instance, the apparent diffusion coefficient can be helpful for identifying tumor borders, or even for classification and/or grading of tumors in e.g. the breast, prostate and liver. More advanced measures derived from DWI, like for instance kurtosis also hold great promise for the oncology-field. In future studies it will be essential to identify the best combination of efficient imaging protocols and analysis techniques that allow a full characterization at the microstructural level in order to achieve the specific goals for the tumor and organ in question.

Low serum 25-hydroxy vitamin D levels are associated with aggressive breast cancer variants and poor prognostic factors in patients with breast carcinoma.

This study was conducted to assess the serum 25-hydroxy (OH) vitamin D levels in patients with breast cancer compared to healthy controls and to identify its association with aggressive breast cancer phenotypes. Serum 25-OH vitamin D levels of 78 breast cancer patients and 78 matched healthy controls were estimated using ELISA. The cases and controls were matched with respect to age, menopausal status, parity, weight, height and co-morbidities. Prognostic factors like grade of tumour, hormone receptor status, HER2 neu status and lymphovascular invasion were compared with 25-OH vitamin D levels. The mean serum 25-OH vitamin D levels of cases were significantly lower compared to the controls (22.33 ± 8.19 vs. 37.41 ± 12.9 ng/mL; p = 0.0001). Patients with higher grades of tumour, non-luminal types of breast cancer and breast cancers with estrogen receptor negativity had significantly lower serum 25-OH vitamin D levels than their opposing groups. Patients with excellent and good Nottingham's prognostic Index (NPI) had significantly higher serum 25-OH vitamin D levels than the moderate and poor NPI groups. Newly diagnosed breast cancer patients have significantly lower serum 25-OH vitamin D levels than healthy controls. Lower level of serum 25-OH vitamin D correlates with aggressive breast cancer phenotypes.

Utility of three dimensional (3-D) ultrasound and power Doppler in identification of high risk endometrial cancer at a tertiary care hospital in southern India: A preliminary study

ObjectiveThe study was conducted to find the utility of three dimensional (3-D) ultrasound and Doppler sonography in differentiating benign and malignant endometrial lesions and to ascertain the association of sonology parameters with type, grade and stage of endometrial cancer. Materials and methodsWomen attending the gynaecology department of a tertiary care hospital, with a provisional diagnosis of carcinoma endometrium were subjected to three dimensional power Doppler ultrasound evaluation and assessment of vascular patterns. VOCAL (Virtual Organ Computer-aided Analysis) software was used to assess volume, Vascularisation Index (VI), Flow Index (FI) and Vascularisation Flow Index (VFI). Ultrasound parameters were compared with histologic diagnosis to evaluate the diagnostic performance using Receiver Operating Characteristic (ROC) Curve. ResultsSixty-four women were included in the study, 33 with benign and 31 with malignant endometrial lesions. Larger endometrial volume and higher Doppler indices correlated with malignant lesions. The variables with good discriminatory potential between benign and malignant status were VI and VFI, having a sensitivity of 90.3% and specificity of around 80%. VFI (adjusted odds ratio of 40.4; (95% CI – 8.46–192.88), p value < 0.001) was the only significant variable identified by multivariate logistic regression, when adjusted for age and post-menopausal status. Multiple global and focal vessel pattern was seen predominantly in malignant cases (specificity 93.9%), although the sensitivity was low (61.2%). Higher stages and grades of tumour and non-endometrioid types had higher Doppler indices, and requires further evaluation. Conclusions3-D ultrasound has good discrimination potential between benign and malignant endometrial lesions and could be useful as a screening tool. However, utility of 3-D tool for differentiation between tumour characteristics needs further validation.

The comparation of B-ultrasound, CTU and IVU in patients with bladder cancer

Objective By means of comparing the value of B-ultrasound, computed tomography urography(CTU)and intravenous urography(IVU) in the screening and diagnosis the patients with bladder cancer, to find the necessary imaging examination in initial diagnosis of bladder cancer. Methods IVU, CTU and ultrasound findings of 280 patients with initially diagnosed bladder cancer from September 2012 to August 2016 in our hospital were reviewed retrospectively. Results Only 3 upper urinary tract tumors were detected with IVU(0.84%), and all the 3 and another 2 upper urinary tract tumors were found out by ultrasonography and CTU.The IVU finding wasn’t correlated with the size, site, number, pathological classification, grading and clinical staging of bladder tumors (P>0.05). Conclusions In the screening, diagnosis and follow-up of the patients with bladder cancer, routine IVU at first diagnosis of bladder cancer is unnecessary.Ultrasound and CTU scanning could be an alternative. Key words: Urinary Bladder Neoplasms; Tomography, X-Ray Computed; Ultrasonography; Urography

PO-301 Diagnosis of glioma tumours using circulating cell-free DNA

IntroductionGliomas are the most frequent tumours of brain, and they make up about 30% of all brain and central nervous system tumours, and 80% of all malignant brain tumours. Diagnosis of different glioma tumour types and their tumour grade is an essential step to suggest a right treatment for the glioma patients. Existing standard diagnostic technique for glioma tumour includes tissue biopsy, which is a highly invasive and hence a risky technique for the patient’s health. ‘Liquid biopsy’ is a new and recently developed non-invasive cancer diagnostic technique. This technique includes collection of blood or urine sample and diagnosis of cancer based on analysing molecular bits or cancer cells that are released from tumour tissue in to the blood or urine system. Circulating cell-free DNA (cfDNA) fragments is one those molecular bits that are released into the bloodstream after the rapid apoptosis or necrosis of the tumour cells in the cancer patients.Material and methodsOur goal is to do the comprehensive study between distinct types of glioma cancer tumours and cfDNA of the respective patients to elucidate the scope of cfDNA in liquid biopsy technique for glioma diagnosis.Results and discussionsWe have successfully detected glioma specific mutations such as IDH1 and 2, PDGFRA, NOTCH1, PIK3R1 etc., on the cfDNA isolated from the plasma of glioma patients and could relate this mutations to the different tumour grades of glioma. We are also studying the dynamics of these mutations in response to the glioma drug treatment by collecting blood samples at different time intervalsConclusionThis study may help in developing liquid biopsy technique for glioma tumour diagnosis and in its prognosis for monitoring the glioma treatment by non-invasive approach, and will eventually help physicians to decide the right treatment on right time and will bypass the existing ‘’wait-and-see’ approach of treatment monitoring.

IDH1(R132H) Immunoexpression in Glioma

Background and objectives: Gliomas are the most common type of primary brain tumors. They result from accumu-- lation of multiple genetic alterations. Isocitrate dehydrogenase 1 mutations are detected in gliomas. This study aimed to assess IDH1 immunoexpression in different types of gliomas and to correlate the results with patient’s age, gender, tumor site, tumor type and grade. Methods:During the period from January 2015 –January 2017, 97 cases of gliomas were collected from Rizgary Teaching Hospital and private laboratories in Erbil city. Typing and grading of tumors were done according to World Health Organization classification of brain tumors 2007.Immunohistochemical staining was done for IDH1 using monoclonal Antibody IDH1R132. Results: Out of 97 cases of gliomas; 16 were grade I, 27 were grade II, 10 were anaplastic gliomas grade III and 44 cases were glioblastomas; grade IV. Positive IDH1 immunoex- pression was observed in 36 (37.1%) cases of gliomas. The highest prevalence of IDH1 was found in the age group 30-44 years (52.8%), in supratentorial tumors (44.3%) and in grade II and III astrocytoma (72.2% and 75%).Highly significant correlation was found between Isocitrate dehydrogenase 1 expression and age of the patients, tumor type and grade while a significant correlation was found between Isocitrate dehydrogenase 1 expression and tumor site. Conclusions:Our study concluded that Isocitrate dehydrogenase 1 is 36 (37.1%) expressed in gliomas and it is sig- nificantly associated with patient’s age, tumor site, histological type and grade, thus it may act as a good diagnostic and prognostic marker for gliomas.

Tumor size correlates with grading in nonfunctioning pancreatic neuroendocrine tumors and is not age-dependent

Tumor size correlates with grading in nonfunctioning pancreatic neuroendocrine tumors and is not age-dependent

Advances and controversies in the classification and grading of pituitary tumors.

Pituitary tumors are common lesions, and they represent the second most frequent primary brain tumor. Their classification has undergone several changes over time. The World Health Organization conducts periodic expert review/consensus meetings and publishes the results as recommendations for changes in classification, based on advances in molecular and genetic advances. This paper summarizes the results of the 2017 WHO Classification, which recommends several important changes. This paper provides a review of the major changes and issues leading to an understanding of the basis for a new pituitary tumor classification. They include the rejection and modification of prior conceptual and pathological characteristics of these neoplasms. There is also considerable concern related to invasive and recurrent pituitary tumors which follow a less benign course than the typical pituitary adenoma. A review of the outcome data for the previously designated "atypical" pituitary tumor category revealed that the former criteria were not adequate to support their ability to predict with accuracy the clinical course of a given tumor. A similar review was accomplished regarding the role of the p53 tumor suppressor mutation. Again, there was no reliable contribution of p53 status to tumor aggressiveness. Other changes have occurred regarding the cytogenetic lineage of the various subtypes of pituitary adenoma. The transcription factors Pit-1, SF-1, and TPit play a major role in determining tumor subtypes and have become part of the classification criteria. These advances now help provide the background for more reliable and consistent classification of pituitary adenomas. Further definition of aggressive characteristics such as cavernous sinus and dural invasion remain to be considered in the quest to make more accurate prognostic projections based on histopathological analysis. The 2017 WHO Classification of Pituitary Tumors provides a more solid basis for accurate and reliable prognostic assessment of these lesions. Further progress undoubtedly will be made as the recommendations of this update are incorporated in to routine use.

Histology-guided proteomic analysis to investigate the molecular profiles of clear cell Renal Cell Carcinoma grades

Renal Cell Carcinoma (RCC) is the most frequent form of kidney cancer and approximately 80% of cases are defined as clear cell RCC (ccRCC). Among the histopathological factors, tumour grade represents one of the most important parameters to evaluate ccRCC progression. Nonetheless, the molecular processes associated with the grading classification haven't been deeply investigated thus far. Therefore, the aim of this study was to uncover protein alterations associated with different ccRCC grade lesions. Formalin-fixed paraffin-embedded samples from ccRCC patients were analysed by histology-guided MALDI-MSI and shotgun proteomics in order to study the biological processes implicated in ccRCC. MALDI-MSI data highlighted signals able to discriminate among different grades (AUC > 0.8). The ion at m/z 1428.92 was identified as Vimentin and was overexpressed in grade 4 lesions, whereas ions at m/z 944.71, m/z 1032.78 and m/z 1325,99 were identified as histones H2A, H3, and H4, respectively. nLC-ESI-MS/MS analysis provided a further list of proteins and their abundances, showing a difference in protein content among the four grades. Moreover, the obtained molecular profiles showed a correspondence with the different Cancer-Specific Survival rate at 10 years post-surgery, as reported in literature. SignificanceDespite the generally accepted role of tumour grade in ccRCC diagnosis, the proteomic processes associated with the different tumour grades has not been extensively studied and doing so may provide insights into the development of the disease. In the current study, data obtained using MALDI-MSI was integrated with that obtained using nLC-ESI-MS/MS to highlight the proteomic alterations underlying the different ccRCC grades. The combined approach identified vimentin and three histones (H2A, H3 and H4) that were able to discriminate among the four grades whilst the nLC-ESI-MS/MS analysis alone provided a further list of proteins with an altered abundance. Furthermore, there was a good correlation between the molecular profiles generated for each grade and the different Cancer-Specific Survival rate at 10 years post-surgery. Such findings could be a valuable starting point for further studies aimed at clarifying the molecular events that occur during the development of ccRCC.