Differentiated Tumor Types Research Articles

Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types.

Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.

Abstract LB056: Crowdsourcing rare cancer research in the Hack4NF GENIE-NF tumor identification and classification challenge

Abstract A key challenge in rare tumor research is the paucity of genomic data that can be used to understand and devise better therapeutic strategies for rare cancers. Furthermore, the “curse of dimensionality,” in which data has many features, such as genetic variants, but few specimens, makes it difficult or impossible to use conventional machine learning techniques to explore these data. To address these challenges in the context of tumors associated with the rare disease neurofibromatosis, we ran a hackathon to stimulate the development of methods to better understand the biology of tumors related to this disease. The hackathon had three challenges centered around variant effect prediction, drug discovery, and genomics. The genomics track of the hackathon leveraged the AACR Project GENIE database (1) and challenged participants to develop new frameworks that accurately use GENIE data to classify neurofibromatosis-related tumors. They were asked to first identify the neurofibromatosis-related tumors in the dataset. They were then asked to use one or more novel classification methods to classify the tumor samples into different groups based on genetic features. To help them do this, we provided access to version 13 of the GENIE database to the hackathon participants, though they were allowed to integrate other relevant datasets. The expected output was a classification method that differentiates different types of NF1, NF2, and schwannomatosis-related tumors using clinical sequencing data, as well as a list of the most important features in the algorithm for differentiating tumor types. Domain expert judges qualitatively scored each team’s rationale for defining and including “NF-related tumors” in their project, and scored the feature list based on the presence of known important biomarkers and features in NF tumors as well as potentially novel features that the algorithm identified. A technical judge also scored the code repository based on documentation and clarity of code. Two teams from the GENIE subchallenge were awarded prizes - Team Next GeNLP as the best overall GENIE challenge submission, and team “Artificial Intelligence for neurofibromatosis” for best project documentation. Both winning teams used methods based on natural language processing (NLP) techniques to reduce the dimensionality and complexity of the variant data, and to identify new representations of NF-relevant tumors, and then applied downstream analysis methods such as distance calculations and feature prioritization to better understand the genomic profiles of different tumors. While these methods and tools focused on NF-specific tumor types, we anticipate that they could be re-used by others to better explore the biology and interrelatedness of other rare tumors within the GENIE database. (1) The AACR Project GENIE Consortium. AACR Project GENIE: Powering Precision Medicine Through An International Consortium, Cancer Discov. 2017. The authors would like to acknowledge the American Association for Cancer Research and its financial and material support in the development of the AACR Project GENIE registry, as well as members of the consortium for their commitment to data sharing. Interpretations are the responsibility of study authors. Citation Format: Robert J. Allaway, Sasha Scott, Gabriel Altay, Hariprasad Donthi, Karthika R, Muhammad Alaa Alwattar, Lucas Pastur Romay, Ayesha Parsha, Jineta Banerjee, Chelsea Nayan, Julie Bletz, Salvatore La Rosa. Crowdsourcing rare cancer research in the Hack4NF GENIE-NF tumor identification and classification challenge [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB056.

Soft-Tissue Sarcomas in Adults in Ecuador in the Period 2010-2020.

Soft-tissue sarcomas (STSs) are rare tumors; they represent 1% of all tumors in adults. There are new diagnostic techniques to differentiate tumor types, and surgery continues to be the most important treatment for STS. This cross-sectional study analyzed the morbidity and mortality caused by STS in adults between 2010 and 2020 using national databases. A total of 8,393 patients hospitalized due to STS were reported. The total number of deaths in Ecuador due to STS was 7,088 over the last decade, the provinces of Pichincha and Guayas registered the highest number of cases, and the mortality rate was 1.2 to 2.0 per 100,000 people. It is noteworthy that the lowest point of registered cases was in 2012. Soft-tissue sarcomas are rare tumors in Ecuador. The morbidity and mortality caused by these tumors have not changed in the last decade. National studies are needed to determine the prevalence of this illness and study intervention to lower mortality.

Advanced Neuroimaging Approaches to Pediatric Brain Tumors.

Simple SummaryAfter leukemias, brain tumors are the most common cancers in children, and early, accurate diagnosis is critical to improve patient outcomes. Beyond the conventional imaging methods of computed tomography (CT) and magnetic resonance imaging (MRI), advanced neuroimaging techniques capable of both structural and functional imaging are moving to the forefront to improve the early detection and differential diagnosis of tumors of the central nervous system. Here, we review recent developments in neuroimaging techniques for pediatric brain tumors. Central nervous system tumors are the most common pediatric solid tumors; they are also the most lethal. Unlike adults, childhood brain tumors are mostly primary in origin and differ in type, location and molecular signature. Tumor characteristics (incidence, location, and type) vary with age. Children present with a variety of symptoms, making early accurate diagnosis challenging. Neuroimaging is key in the initial diagnosis and monitoring of pediatric brain tumors. Conventional anatomic imaging approaches (computed tomography (CT) and magnetic resonance imaging (MRI)) are useful for tumor detection but have limited utility differentiating tumor types and grades. Advanced MRI techniques (diffusion-weighed imaging, diffusion tensor imaging, functional MRI, arterial spin labeling perfusion imaging, MR spectroscopy, and MR elastography) provide additional and improved structural and functional information. Combined with positron emission tomography (PET) and single-photon emission CT (SPECT), advanced techniques provide functional information on tumor metabolism and physiology through the use of radiotracer probes. Radiomics and radiogenomics offer promising insight into the prediction of tumor subtype, post-treatment response to treatment, and prognostication. In this paper, a brief review of pediatric brain cancers, by type, is provided with a comprehensive description of advanced imaging techniques including clinical applications that are currently utilized for the assessment and evaluation of pediatric brain tumors.

Genome-wide DNA methylation profiling and identification of potential pan-cancer and tumor-specific biomarkers.

DNA methylation alterations have already been linked to cancer, and their usefulness for therapy and diagnosis has encouraged research into the human epigenome. Several biomarker studies have focused on identifying cancer types individually, yet common cancer and multicancer markers are still underexplored. We used The Cancer Genome Atlas (TCGA) to investigate genome‐wide methylation profiles of 14 different cancer types and developed a three‐step computational approach to select candidate biomarker CpG sites. In total, 1991 pan‐cancer and between 75 and 1803 cancer‐specific differentially methylated CpG sites were discovered. Differentially methylated blocks and regions were also discovered for the first time on such a large scale. Through a three‐step computational approach, a combination of four pan‐cancer CpG markers was identified from these sites and externally validated (AUC = 0.90), maintaining comparable performance across tumor stages. Additionally, 20 tumor‐specific CpG markers were identified and made up the final type‐specific prediction model, which could accurately differentiate tumor types (AUC = 0.87–0.99). Our study highlights the power of the methylome as a rich source of cancer biomarkers, and the signatures we identified provide a new resource for understanding cancer mechanisms on the wider genomic scale with strong applicability in the context of new minimally invasive cancer detection assays.

The Clinical Significance of CA19-9 and Tumor Size Ratios for Predicting Prognosis After Conversion Surgery in Patients With Stage IV Gastric Cancer.

The clinical benefit of conversion surgery (CS) after chemotherapy remains unclear for stage IV gastric cancer (GC) patients. This study aimed to investigate the prognostic factors used to determine whether CS is a promising therapeutic strategy. We retrospectively analyzed data from 156 patients diagnosed with unresectable stage IV GC who underwent chemotherapy as the initial treatment, including 40 patients who had R0 resection in CS. The median survival time of the CS patients was significant longer than that of patients who underwent chemotherapy alone. A multivariate analysis identified only pN3 as an independent prognostic factor in CS patients. Among the differentiated tumor type patients, carbohydrate antigen 19-9 (CA19-9) levels were significantly higher in pN3 patients than in pN0-2 patients before chemotherapy. Among undifferentiated tumor type patients, pN3 patients had a significantly lower tumor size ratio (before chemotherapy/before surgery) than pN0-2 patients. Although it is clinically difficult to diagnose lymph node metastasis using preoperative examinations, CA19-9 levels and tumor size ratios may be preoperative indicators for predicting pN3, which is associated with a poor prognosis in CS.

Características de textura del tumor primario en imágenes de 18F-FDG PET en cáncer de pulmón de células no pequeñas: la relación entre parámetros de imágenes y parámetros histopatológicos

ObjectivesThe aims of this study were to evaluate the relationships between textural features of the primary tumor on FDG PET images and clinical-histopathological parameters which are useful in predicting prognosis in newly diagnosed non-small cell lung cancer (NSCLC) patients. Material and methodsPET/CT images of ninety (90) patients with NSCLC prior to surgery were analyzed retrospectively. All patients had resectable tumors. From the images we acquired data related to metabolism (SUVmax, metabolic tumor volume [MTV] and total lesion glycolysis [TLG]) and texture features of primary tumors. Histopathological tumor types and subgroups, degree of Ki-67 expression and necrosis rates of the primary tumor, mediastinal lymph node (MLN) status and nodal stages were recorded. ResultsAmong the 2histologic tumor types (adenocarcinoma and squamous cell carcinoma) significant differences were present regarding metabolic parameters, Ki-67 index with higher values and kurtosis with lower values in the latter group. Textural heterogeneity was found to be higher in poorly differentiated tumors compared to moderately differentiated tumors in patients with adenocarcinoma. While Ki-67 index had significant correlations with metabolic parameters and kurtosis, tumor necrosis rate was only significantly correlated with textural features. By univariate and multivariate analyses of the imaging and histopathological factors examined, only gradient variance was significant predictive factor for the presence of MLN metastasis. ConclusionsTextural features had significant associations with histologic tumor types, degree of pathological differentiation, tumor proliferation and necrosis rates. Texture analysis has potential to differentiate tumor types and subtypes and to predict MLN metastasis in patients with NSCLC.

Hepatic vascular malignancies in children are associated with increased rates of surgical resection and improved overall survival compared with adults.

Hepatic vascular malignancies (HVMs) are rare malignancies, with no standardized treatment regimens. The most common HVMs, angiosarcoma and malignant epithelioid hemangioendothelioma (EHE), are often grouped together in the literature complicating our ability to achieve reliable survival data and treatment strategies. To compare the disease characteristics of HVMs, with a subanalysis on pediatric patients. The 2016 National Cancer Database was queried for patients with HVMs using international classification of diseases-oncology-3 (ICD-O-3) codes yielding 699 patients. Descriptive statistics, chi-square, Kaplan-Meier, and log-rank analyses were performed. We found 478 patients (68%) with angiosarcoma and 221 (32%) with EHE. The median (Q1, Q3) age for angiosarcoma patients was 65years (56, 75) versus 54years (37, 65) in EHE patients (P<.001). The rate of resection was lower in patients with angiosarcoma than EHE (13% vs 32%, P<.001). The mean 1-, 3-, and 5-year overall survival for angiosarcoma patients was 17%, 8%, and 6%, respectively, versus 80%, 65%, and 62% in EHE patients (P<.0001). A subgroup analysis was performed on pediatric patients demonstrating six with angiosarcoma and 10 with EHE. The mean 1-, 3-, and 5-year overall survival for pediatric angiosarcoma patients was 67%, 50%, and 50%, respectively, and 90%, 90%, and 90% for pediatric EHE patients. In the largest study of HVMs to date, we found angiosarcoma has significantly worse overall survival than EHE. Pediatric patients appear to have improved survival and higher rates of resection. Larger studies of HVMs are needed to clearly differentiate tumor types, standardize care, and improve survivorship.

Age and Tumor Differentiation-Associated Gene Expression Based Analysis of Non-Familial Prostate Cancers.

Prostate cancer incidence in young men has increased. Patients diagnosed at an earlier age are likely to have aggressive prostate cancer and treatment decisions are continuing to be weighted by patient age and life expectancy. Identification of age-associated gene-expression signatures hold great potential to augment current and future treatment modalities. To investigate age-specific tumor associated gene signatures and their potential biomarkers for disease aggressiveness, this study was designed and stratified into well and poorly differentiated tumor types of young (42–58 years) and old (66–73 years) prostate cancer patients. The differentially expressed genes related to tumor-normal differences between non-familial prostate cancer patients were identified and several genes uniquely associated with the age and tumor differentiation are markedly polarized. Overexpressed genes known to be associated with somatic genomic alterations was predominantly found in young men, such as TMPRESS2-ERG and c-MYC. On the other hand, old men have mostly down-regulated gene expressions indicating the loss of protective genes and reduced cell mediated immunity indicated by decreased HLA-A and HLA-B expression. The normalization for the benign signatures between the age groups indicates a significant age and tumor dependent heterogeneity exists among the patients with a great potential for age-specific and tumor differentiation-based therapeutic stratification of prostate cancer.

Texture features of primary tumor on 18F-FDG PET images in non-small cell lung cancer: The relationship between imaging and histopathological parameters

PurposeThe aims of this study were to evaluate the relationships between textural features of the primary tumor on FDG PET images and clinical-histopathological parameters which are useful in predicting prognosis in newly diagnosed non-small cell lung cancer (NSCLC) patients. MethodsPET/CT images of ninety (90) patients with NSCLC prior to surgery were analyzed retrospectively. All patients had resectable tumors. From the images we acquired data related to metabolism (SUVmax, MTV, TLG) and texture features of primary tumors. Histopathological tumor types and subgroups, degree of Ki-67 expression and necrosis rates of the primary tumor, mediastinal lymph node (MLN) status and nodal stages were recorded. ResultsAmong the two histologic tumor types (adenocarcinoma and squamous cell carcinoma) significant differences were present regarding metabolic parameters, Ki-67 index with higher values and kurtosis with lower values in the latter group. Textural heterogeneity was found to be higher in poorly differentiated tumors compared to moderately differentiated tumors in patients with adenocarcinoma. While Ki-67 index had significant correlations with metabolic parameters and kurtosis, tumor necrosis rate was only significantly correlated with textural features. By univariate and multivariate analyses of the imaging and histopathological factors examined, only gradient variance was significant predictive factor for the presence of MLN metastasis. ConclusionsTextural features had significant associations with histologic tumor types, degree of pathological differentiation, tumor proliferation and necrosis rates. Texture analysis has potential to differentiate tumor types and subtypes and to predict MLN metastasis in patients with NSCLC.

Prognostic impact of Borrmann classification on advanced gastric cancer: a retrospective cohort from a single institution in western China

BackgroundDue to the controversy over the prognostic significance of Borrmann type in patients with gastric cancer (GC), the present study was to investigate the clinical value of Borrmann type in advanced GC.MethodsWe retrospectively evaluated 2092 patients with advanced GC and subsequently examined the clinicopathological characteristics and prognosis of patients stratified by Borrmann type.ResultsPatients were divided into three groups according to Borrmann type (Borrmann types I+II, III, and IV). Patients with Borrmann types III and IV had larger size, more poorly differentiated tumor type, more advanced tumor stage, and higher chance of involving the entire stomach. The overall survival (OS) rates were significantly different among the three groups (p < 0.001). Stratification analysis revealed significant OS rates among the three groups in tumor-node-metastasis (TNM) stage III (p < 0.001) and TNM stage IV (p = 0.008). Multivariate analysis revealed that Borrmann types, adjuvant chemotherapy, curative resection, and TNM stage were all independent predictors of OS among GC patients. The subgroup analysis indicated that Borrmann type was an independent predictor of OS among GC patients who undergone curative resection and with TNM stage III cancer. However, curative resection and postoperative chemotherapy failed to prolong the survival of patients with Borrmann type IV.ConclusionsThe clinicopathological characteristics and prognosis of patients with three Borrmann types of GC were different. Borrmann type can be simply used as a valuable factor to predict survival in advanced GC patients, especially in those TNM stage III undergoing curative resection. Additionally, more attention should be paid to the treatment for Borrmann type IV GC.

Vitamin D regulation of HAS2, hyaluronan synthesis and metabolism in triple negative breast cancer cells

The vitamin D receptor (VDR) and its ligand 1,25(OH)2D3 (1,25D) exert anti-tumor effects, but considerable heterogeneity has been reported in different model systems. In general, cell lines derived from aggressive tumor subtypes such as Triple Negative Breast Cancer (TNBC) express low levels of VDR and are less sensitive to 1,25D than those derived from more differentiated tumor types. We have previously reported that 1,25D inhibits hyaluronic acid synthase 2 (HAS2) expression and hyaluronic acid (HA) synthesis in murine TNBC cells. Here we confirmed the inhibitory effect of 1,25D on HA synthesis in human Hs578T cells representative of the mesenchymal/stem-like (MSL) subtype of TNBC. Because HA synthesis requires the production of hexoses for incorporation into HA, we predicted that the high HA production characteristic of Hs578T cells would require sustained metabolic changes through the hexosamine biosynthetic pathway (HBP). We thus examined metabolic gene expression in Hs578T cell variants sorted for High (HAHigh) and Low (HALow) HA production, and the ability of 1,25D to reverse these adaptive changes. HAHigh populations exhibited elevated HA production, smaller size, increased proliferation and higher motility than HALow populations. Despite their more aggressive phenotype, HAHigh populations retained expression of VDR protein at levels comparable to that of parental Hs578T cells and HALow subclones. Treatment with 1,25D decreased production of HA in both HAHigh and HALow populations. We also found that multiple metabolic enzymes were aberrantly expressed in HAHigh cells, especially those involved in glutamine and glucose metabolism. Notably, Glutaminase (GLS), a known oncogene for breast cancer, was strongly upregulated in HAHigh vs. HALow cells and its expression was significantly reduced by 1,25D (100 nM, 24 h). Consistent with this finding, Seahorse extracellular flux analysis indicated that respiration in HAHigh cells was significantly more dependent on exogenous glutamine than HALow cells, however, acute 1,25D exposure did not alter metabolic flux. In contrast to GLS, the glutamate transporter SLC1A7 was significantly reduced in HAHigh cells compared to HALow cells and its expression was enhanced by 1,25D. These findings support the concept that 1,25D can reverse the metabolic gene expression changes associated with HA production in cancer cells with aggressive phenotypes.

Morphofunctional features of non-functioning pituitary adenomas

Non-functioning pituitary adenomas (NFPAs) account for about 30% of all pituitary tumors. NFPAs are characterized by the lack of secretory potential or its weak expression insufficient for determination of the blood level of adenohypophyseal tropic hormones and for development of a specific clinical picture. Morphologically, NFPAs are a heterogeneous group of tumors, the classification of which was previously based only on immunoreactivity for pituitary tropic hormones. The WHO revised its Classification of Tumors of Endocrine Organs (4th edition) in 2017. The main changes relate to adenohypophysial-cell lineage for the designation of adenomas into subtypes. The introduction of transcription factor antibodies has become a fundamentally new approach to the classification of NFPAs, which is necessary to recognize less differentiated tumor types. This paper provides information on the new histopathological classification of pituitary adenomas, on the theories of silent adenomas, and on the proliferative and prognostic markers of NFPAs.

A Promising Method for Tumor Localization during Total Laparoscopic Distal Gastrectomy: Preoperative Endoscopic Clipping based on Negative Biopsy and Selective Intraoperative Radiography Findings.

PurposePrecise localization of tumors and creation of sufficient proximal resection margins are complicated processes during total laparoscopic distal gastrectomy (TLDG) for clinical T1/T2 gastric cancers. Various solutions to this problem have also yielded many disadvantages. In this study, we reviewed a preoperative endoscopic clipping method based on the results of negative biopsy and selective intraoperative radiography.Materials and MethodsA retrospective review of 345 consecutive patients who underwent TLDG and preoperative endoscopic clipping for tumor localization was conducted. During preoperative endoscopy, the endoscopists performed negative biopsies just 1–2 cm selectively above the tumor's upper limit. After confirming the biopsy results, endoscopic metal clips were applied just proximal to the negative biopsy site the day before surgery. Selective intraoperative tumor localization using portable abdominal radiography was performed only when we could not ensure a precise resection line.ResultsNegative biopsy was performed in 244 patients. Larger tumor size (P=0.008) and more distally located tumors (P=0.052) were observed more frequently in the negative biopsy group than in the non-negative biopsy group. The non-negative biopsy group had significantly higher frequencies of differentiated tumor types than the negative biopsy group (P=0.003). Of the 244 patients who underwent negative biopsies, 6 had cancer cells in their biopsy specimens. We performed intraoperative radiography in 12 patients whose tumors had difficult-to-determine proximal margins. No tumors were found in the proximal resection margins of any patients.ConclusionsOur tumor localization method is a promising and accurate method for securing a sufficient resection margin during TLDG.

Testing for Multivariate Normality in Mass Spectrometry Imaging Data: A Robust Statistical Approach for Clustering Evaluation and the Generation of Synthetic Mass Spectrometry Imaging Data Sets.

Spatial clustering is a powerful tool in mass spectrometry imaging (MSI) and has been demonstrated to be capable of differentiating tumor types, visualizing intratumor heterogeneity, and segmenting anatomical structures. Several clustering methods have been applied to mass spectrometry imaging data, but a principled comparison and evaluation of different clustering techniques presents a significant challenge. We propose that testing whether the data has a multivariate normal distribution within clusters can be used to evaluate the performance when using algorithms that assume normality in the data, such as k-means clustering. In cases where clustering has been performed using the cosine distance, conversion of the data to polar coordinates prior to normality testing should be performed to ensure normality is tested in the correct coordinate system. In addition to these evaluations of internal consistency, we demonstrate that the multivariate normal distribution can then be used as a basis for statistical modeling of MSI data. This allows the generation of synthetic MSI data sets with known ground truth, providing a means of external clustering evaluation. To demonstrate this, reference data from seven anatomical regions of an MSI image of a coronal section of mouse brain were modeled. From this, a set of synthetic data based on this model was generated. Results of r2 fitting of the chi-squared quantile-quantile plots on the seven anatomical regions confirmed that the data acquired from each spatial region was found to be closer to normally distributed in polar space than in Euclidean. Finally, principal component analysis was applied to a single data set that included synthetic and real data. No significant differences were found between the two data types, indicating the suitability of these methods for generating realistic synthetic data.

Incidence of lymph node metastasis in intramucosal gastric cancer measuring 30 mm or less, with ulceration; mixed, predominantly differentiated-type histology; and no lymphovascular invasion: a multicenter retrospective study

Intramucosal gastric cancer, ≤3cm (≤30 mm) with ulceration, and mixed histology (predominantly differentiated), was previously considered curative after endoscopic resection, and additional surgery was thought to be unnecessary. However, as the evidence base for these criteria remains insufficient, the Japanese Gastric Cancer Treatment Guidelines, ver. 3 (2010) specify that this pathology should be considered noncurative and recommend additional surgery. We report the frequency of lymph node metastasis in patients with these conditions based on a multicenter study. Of patients with early gastric cancer who underwent gastrectomy with lymph node dissection, those with a mixed, predominantly differentiated tumor type, ulceration, a tumor diameter ≤3cm, and no lymphovascular invasion were entered into this study. Four hundred and seven patients met the criteria, 21 of whom were excluded owing to a lack of available information. Thus, a total of 386 patients were included in the analysis, from 37 of the 42 member institutions. The mean study duration was 125months. The most common combination of mixed histology was tub2+por (67%). None of the 386 patients had lymph node metastasis (95% confidence interval, 0-0.8%). The results of this retrospective study indicate that the risk of lymph node metastasis was less than 1% among patients with the criteria defined here, considered to be criteria for noncurative resection as per the current guidelines, and suggest that observation alone without additional surgery may result in a good outcome.

SU‐E‐J‐225: CEST Imaging in Head and Neck Cancer Patients

Purpose:Chemical Exchange Saturation Transfer (CEST) imaging is an MRI technique enables the detection and imaging of metabolically active compounds in vivo. It has been used to differentiate tumor types and metabolic characteristics. Unlike PET/CT,CEST imaging does not use isotopes so it can be used on patient repeatedly. This study is to report the preliminary results of CEST imaging in Head and Neck cancer (HNC) patients.Methods:A CEST imaging sequence and the post‐processing software was developed on a 3T clinical MRI scanner. Ten patients with Human papilloma virus positive oropharyngeal cancer were imaged in their immobilized treatment position. A 5 mm slice CEST image was acquired (128×128, FOV=20∼24cm) to encompass the maximum dimension of tumor. Twenty‐nine off‐set frequencies (from −7.8ppm to +7.8 ppm) were acquired to obtain the Z‐spectrum. Asymmetry analysis was used to extract the CEST contrasts. ROI at the tumor, node and surrounding tissues were measured.Results:CEST images were successfully acquired and Zspectrum asymmetry analysis demonstrated clear CEST contrasts in tumor as well as the surrounding tissues. 3∼5% CEST contrast in the range of 1 to 4 ppm was noted in tumor as well as grossly involved nodes. Injection of glucose produced a marked increase of CEST contrast in tumor region (∼10%). Motion and pulsation artifacts tend to smear the CEST contrast, making the interpretation of the image contrast difficult. Field nonuniformity, pulsation in blood vesicle and susceptibility artifacts caused by air cavities were also problematic for CEST imaging.Conclusion:We have demonstrated successful CEST acquisition and Z‐spectrum reconstruction on HNC patients with a clinical scanner. MRI acquisition in immobilized treatment position is critical for image quality as well as the success of CEST image acquisition. CEST images provide novel contrast of metabolites in HNC and present great potential in the pre‐ and post‐treatment assessment of patients undergoing radiation therapy.

The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases--preliminary study.

Brain metastases (BM) in non-small-cell lung cancer (NSCLC) patients present an increasing clinical challenge. Identifying biomarkers which specifically identify patients at high risk of BM may improve their early diagnosis, which is crucial for surgical and radiotherapeutic treatment outcome. Alpha-2,6-sialyltransferase (α-2,6-ST) and the primary product of its activity, alpha-2,6-galactose-linked sialic acids (α-2,6-GalSA) have been found responsible for the adhesion of tumor cells to the brain vessels' endothelium and enabling their transmigration through the blood-brain barrier in brain metastatic tumors. The aim of the study was to investigate by histochemical method the presence and possible role of α-2,6-GalSA in the formation of brain metastasis in NSCLC. In the screening phase 76 metastatic brain tumors were stained for α-2,6-GalSA and the second phase involved an identical staining of 20 primary tumors of patients who had their primary tumors treated with surgery or definite radiochemotherapy yet who later developed BM. The results were compared to a control group of 22 patients treated with surgery for NSCLC and who survived 5 years without the recurrence of disease. Alpha-2,6-GalSA presence was found to be down-regulated in poorly differentiated tumor types, whereas majority of differentiated tumors overexpressed it. This was statistically significant for both BM and the primary tumors. The expression of α-2,6-GalSA remained stable in primary and metastatic tumor pairs, however, no statistically significant differences were observed between study and control groups. Within the study group, a higher α-2,6-GalSA expression was associated with better overall survival, but not all statistical models found this result significant. Further studies are recommended to validate these findings.

Ongoing comparison of confocal laser endomicroscopy (PCLE) pulmonary images with surgical biopsies for lung cancer diagnosis

<h3>Background</h3> Probe-based confocal laser endomicroscopy (pCLE) is a new FDA approved tool used for in vivo microscopic imaging of proximal and distal airways including bronchial and alveolar walls, microvessels, and inflammatory cells. Light at 488 nm wavelength is focused via a pinhole-sized aperture incorporated into a flexible probe that fits into the working channel of a standard bronchoscope and reflected back through that aperture to produce an image that can aid in the identification of neoplastic processes. Studies have demonstrated elastin and collagen fibers as having endogenous fluorescence by pCLE. No studies have correlated in vivo imaging by pCLE to pathologic samples obtained during bronchoscopy. This combination could prove diagnostically advantageous to both clinician and pathologist. <h3>Design</h3> Selected patients undergoing bronchoscopy from 7/17/ 12 to present are subjected to pCLE followed by biopsy. pCLE and bronchoscopy are performed to help determine abnormal bronchial or alveolar changes that warrant a biopsy. We correlate pCLE images with biopsies obtained during bronchoscopy. Patients ranged from 47 to 82 years of age, and biopsies include adeno, squamous cell, poorly differentiated, small cell and metastatic carcinomas. When necessary, immunohistochemistry (IHC) and electron microscopy (EM) are performed for further tumor classification. Studies are ongoing to add additional tumor types. <h3>Results/findings</h3> By pCLE, differences between normal, inflammation and neoplasia can be recognized. Normal findings consist of organized connective tissue fibers. Inflammatory cells, mostly macrophages, can be recognized within tissue spaces. In neoplastic tissue, a ragged surface can be observed along with disorganization of the collagen/elastin fibers within the bronchi/ alveoli. Differences between squamous (SCC) and adenocarcinomas (ADC) can be suggested on the basis of imaging patterns. SCC shows friability and dense areas of auto fluorescence with dark spots representing tumor groups. ADC shows less fluorescence and gives a mottled appearance to the tissue. ADC with bronchioloalveolar differentiation and a lepidic pattern of growth can be suspected when a studded appearance is noted by pCLE. Disarray of fibers increases with more poorly differentiated carcinomas. Biopsies and pCLE images can be correlated by comparing tissue patterns with images. The use of IHC and ultrastructural evaluation (EM) further support our pCLE and microscopic findings. <h3>Conclusions</h3> pCLE allows the distinction between benign and malignant tissues, assists in obtaining diagnostic tissue, and recognizes tumor growth patterns. Correlation between biopsies and pCLE can help aid sampling and diagnostic techniques. Larger studies can enhance our understanding of how pCLE can help differentiate tumor types.

Histopathologic Findings of Small Renal Tumor Biopsies Performed Immediately After Cryoablation Therapy

To evaluate the histopathology of small renal tumor biopsies following cryoablation. We retrospectively evaluated small renal tumor biopsy specimens after cryoablation treatment for renal cell carcinoma and determined the ability to differentiate tumor types, effect on nuclear grading, immunohistochemical staining, and if the number of freeze cycles affected interpretation. Of the biopsy specimens, 66% were diagnostic of tumor and 34% showed normal renal parenchyma. Tumor subtype was determined in 91% of diagnostic cases. Nuclear grading was affected due to freeze effect, complicating the assessment of chromatin pattern and nucleolar details at low magnification. In particular, the distinction between Fuhrman nuclear grades I and II was compromised; these were designated as low nuclear grade. Immunohistochemical staining was retained similar to untreated tumors. Tumor subtyping was not affected after one or two freeze cycles. Biopsies performed immediately after cryoablation can be used to render an optimal histologic diagnosis.