Non-recurrent Tumours Research Articles

The extracapsular dissection technique in the management of benign tumours of the parotid gland: our experience in 194 patients.

The indications for and approaches to extracapsular dissection for parotid gland benign tumours are debated in the literature. This study retrospectively evaluates a single site's short- and long-term results with a standardised extracapsular dissection approach to benign parotid tumours. A retrospective review of a single institution's records identified cases with extracapsular dissection as the primary surgery for non-recurrent benign parotid tumours. A total of 194 eligible patients were identified (124 women and 70 men, age 47.75 ± 15.62 years). Pre-, intra- and post-surgical data were reviewed for complications and recurrences. Histology reported pleomorphic adenoma in 165 patients, Warthin's tumour in 28 patients and both in one patient. Mean follow up was 36 ± 16 months (range, 12-84 months). The incidences of complications following extracapsular dissection were temporary (n = 13) and permanent (n = 0) facial nerve dysfunction, Frey's syndrome (n = 1)) and recurrences (n = 5). These rates align with prior literature. This case series shows how a standardised approach to extracapsular dissection for benign parotid tumours yields favourable results, supporting a progressive change of strategy towards reduced invasiveness.

Elevated translationally controlled tumour protein promotes oral cancer progression and poor outcome.

Translationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1. TCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft-agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan-Meier and Cox regression. TCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non-recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co-expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard-ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells. Our studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers.

RF05 A national report on incidence, patient demographics and tumour characteristics of melanoma by BRAF, NRAS and KIT genotype: England 2016–2019

Abstract Although studies have shown variation between countries in the incidence and characteristics of patients and tumours associated with melanoma BRAF, NRAS and KIT mutations, no national molecular genetics data from England have been published. In 2022, the National Institute for Health and Care Excellence highlighted the need for national cohort studies to evaluate the role of biomarkers. This descriptive national observational study used National Disease Registration Service (NDRS) data to identify all site melanoma cases that were diagnosed and underwent molecular genetic testing in England between 2016 and 2019. The NDRS collects molecular genetics data from most genomic laboratories nationally but does not routinely receive results for BRAF testing by immunohistochemistry (IHC) done at local pathology laboratories. Molecular genetic testing and incidence of wild-type (WT), BRAF mutant (+), NRAS+ and KIT+ melanomas were described. Demographic (sex, age, ethnicity, deprivation, geographical region) and tumour factors (site, stage) of BRAF+, NRAS+, KIT+ and WT tumours were described. In total, 61 514 new melanomas were registered in England between 2016 and 2019. Thirteen per cent (n = 7925), 5.0% (n = 3084) and 1.2% (n = 743) of tumours underwent BRAF, NRAS and KIT testing, respectively. BRAF testing rates varied across regions from 19.9% (n = 1040/5217) in the West Midlands to 5.5% (n = 227/4114) in the North East. Thirty-four per cent (n = 2674/7925), 30.5% (n = 942/3084) and 8.6% (n = 64/743) of tumours were BRAF+, NRAS+ and KIT+, respectively. Thirty-four per cent (n = 1523/4479) of males and 37.6% (n = 1132/3014) of females with cutaneous melanomas were BRAF+. Forty-six per cent (n = 1693/3712) of patients aged &amp;lt; 70 years and 20.5% (n = 332/1622) aged ≥ 80 years were BRAF+. The highest proportion of BRAF+ cutaneous melanoma were identified in the North East (46.7%, n = 106/227) and the lowest in the West Midlands (32.6%, n = 339/1040). Thirty-two per cent (n = 560/1760) of males and 30.0% (n = 349/1167) of females with cutaneous melanoma were NRAS+. Twenty-six per cent (n = 356/1354) of patients aged &amp;lt; 70 years and 31.8% (n = 229/718) aged ≥ 80 years were NRAS+. The highest proportion of NRAS+ cutaneous melanoma were in the West Midlands (40%, n = 14/35) and the lowest in the North East (28.3%, n = 36/127). We report the largest and most complete dataset for national molecular genetics of melanoma ever published. Regional differences in BRAF testing may be explained by variations in local practice and methods used, and differences in population age, but could impact on treatment options. Lack of IHC, testing nonuniformity and lack of whole melanoma population data (early-stage nonrecurrent tumours and tumours in frail elderly patients may be excluded) were limitations.

Depression, anxiety and health-related quality of life in paediatric intracranial germ cell tumor survivors

BackgroundLittle is known about depression and anxiety among paediatric intracranial germ cell tumour (iGCT) survivors. We aimed to evaluate the risk factors associated with depression, anxiety and health-related quality of life (HRQoL) in paediatric iGCT survivors.MethodsWe recruited 200 iGCT patients (and their parents) from Beijing Tiantan Hospital and assessed their HRQoL using the Paediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales. The Children’s Depression Inventory, Screen for Child Anxiety Related Emotional Disorders, and Symptom Checklist 90 were used to evaluate depression and anxiety. The results were analysed based on disease recurrence, tumour location and treatment strategies.ResultsSurvivors with recurrent tumours had worse HRQoL scores than those with non-recurrent tumours. Patients with tumours involving both the suprasellar and basal ganglia regions had the worst HRQoL scores. A large proportion of survivors had depression or anxiety. Both depression and anxiety scores were highly correlated with the HRQoL emotional functioning scores. The parent proxy-reports (PPR) and child self-reports were highly correlated in all domains.ConclusionsThis study demonstrated the clinical factors affecting paediatric iGCT survivors’ depression, anxiety, and HRQoL. Therefore, psychological interventions should be implemented. It also suggests that the PedsQL PPR would be helpful for routine screening.

Evaluation of Tumor-Infiltrating Lymphocytes as a Prognostic Indicator of Head-and-Neck Squamous Cell Carcinomas

Introduction: The incidence of Head-and-Neck Squamous Cell Carcinomas (HNSCC) is on the rise in our country and worldwide, with a worsening prognosis. The abundance of tumor-infiltrating lymphocytes (TILs) is evolving to be a novel prognostic indicator in assessing treatment response of HNSCC. TILs mainly comprise T lymphocytes, which migrate from blood into the tumor as part of the body's immune response. In this context, targeting the tumor microenvironment with the help of immunotherapy may present a potential approach for better cure of head-and-neck cancers. In the present study, we evaluated the potential TILs parameters which can be used in clinical practice to predict treatment outcomes in HNSCC. Materials and Methods: This is a prospective observational study of 41 patients conducted at a tertiary cancer center between September 2019 and September 2020. All patients with biopsy proven, primary/recurrent HNSCC, without distant metastasis, and complete clinicopathological data were included in the study. Patients with a nonsquamous cell carcinoma, patients who underwent upfront chemotherapy or chemoradiotherapy were excluded from the study. Patients who had follow-up of &lt;1 year or lost to follow-up were excluded from the study. Parameters analyzed include mean age; percentage of cluster of differentiation 3 (CD3) cells; CD4, CD8, and FOXP3cell counts; distribution of CD57 and CD3/FOXP3 ratio. Results: A total number of 19 patients were grouped under the nonrecurrence TILs and 22 patients under recurrent TILs category. Majority of the patients (90.2%) had oral cavity squamous cell carcinoma. 68.42% of nonrecurrent cases and 36.36% of recurrent cases were found to be harboring Hot tumors. Using odds ratio, it was noted that the odds of having Hot tumor is 3.79 times (95% confidence interval: [1.03,13.91]) higher in nonrecurrent TILs than in recurrent TILs group. CD3 cell count was higher in nonrecurrent cases (54.74 ± 18.37) than in recurrent cases (42.73 ± 16.09) with P = 0.0157. Using two tailed t-test, it was noted that the mean of CD4, CD8, and FOXP3 is not significantly different between nonrecurrent and recurrent tumor TILs groups. Conclusion: To summarize, we have shown that the CD3/FOXP3 cell ratio, rather than the individual proportion of TILs, is a significant prognostic indicator in HNSCC. It's also been shown that people with Cold tumors have a higher risk of recurrence than those with Hot tumors. Our findings confirm the importance of host immunity in prognosis and suggest that the degree of immune cell infiltration in the tumor microenvironment is a major independent prognostic factor that merits further investigation as a potentially valuable biomarker in HNSCC patients.

Identifying the mRNAs associated with Bladder cancer recurrence.

To identify the mRNAs associated with bladder cancer (BC) recurrence. The transcription profile of GSE31684 including 39 recurrent BC tumor samples and 54 non-recurrent BC tumor samples as well as transcription profile of GSE13507 including 36 recurrent BC tumor samples and 67 non-recurrent BC tumor samples were downlaoded from the Gene Expression Omnibus. Then, the differentially expressed genes (DEGs) were identified using linear models for microarray data (limma) and the intersections of DEGs from the two datasets were further screened. The weighed gene co-expression network analysis (WGCNA) was used to screen the modules related to BC recurrence. Protein-protein interaction (PPI) network analysis was used to analyze the genes interaction. Their functions were predicted by Gene Ontology and KEGG pathway enrichment. Moreover, The Comparative Toxicogenomics Database 2017 update (CTD) was used to search the BC related pathway. The univariate cox regression analysis was used to identify DEGs associated to the recurrence. Kaplan-Meier plots were used to illustrate recurrence free survival time (RFS). A total of 692 intersections DEGs were screened. WGCNA showed that 7 modules (2279 genes) were stable in both the datasets. A total of 169 intersection DEGs were mapped to the 7 modules. There existed 149 interaction relationships among 81 proteins (18 down-regulated and 63 up-regulated DEGs) in the PPI network. Two KEGG pathways including Focal adhesion and ECM-receptor interaction were enriched which were also found in the CTD. The univariate cox regression analysis showed that 3 DEGs (COL4A1, COL1A2 and COL5A1) were significant related to the prognosis. Multivariate cox regression analysis revealed that pathologic_N (N0-N1 vs N2-N3, p= 0.033) were independent prognostic factors for overall survival in patients with BC. COL4A1, COL1A2 and COL5A1 could be associated with BC recurrence.

Sparsity of dendritic cells and cytotoxic T cells in tumor microenvironment may lead to recurrence in basal cell carcinoma.

Antitumor immune response affects tumor growth. The effect of antitumor immune response on recurrence has been poorly studied in basal cell carcinoma (BCC). To investigate the effects of the peritumoral immune infiltrate on BCC recurrence. A total of 30 BCC patients without recurrence and 29 BCC patients with recurrence were included in this retrospective study. Non-recurrent tumor samples as well as primary and recurrent tumor samples from the recurrent group were stained immunohistochemically with anti-CD4, CD8, CD25, FOXP3, CD68, CD163, and CD1a antibodies. Immune infiltrates were semiquantitatively evaluated. BCC tumor microenvironment was rich in CD4+ cells. CD163 expression was higher than CD68. In primary tumors of the recurrent group, CD8 expression was significantly lower than CD4 expression. CD1a expression was lower in primary tumors of the recurrent group than in nonrecurrent tumors. Our results suggest the existence of an immunosuppressive microenvironment in BCC. Lower CD8+ T-cell numbers and sparsity of dendritic cells in primary tumors of recurrent patients suggest further immunosuppression in the tumor microenvironment and an increase in recurrence risk. This is the first study that evaluates and compares tumor immune microenvironments of primary and recurrent BCC lesions with several markers and investigates the role of antitumor immunity on BCC recurrence.

Histopathologic Patterns of Recurrent Choroidal Melanoma Following I-125 Plaque Brachytherapy

Purpose: Histologic correlation of clinical patterns of recurrent choroidal melanoma following I-125 plaque brachytherapy was performed to identify pathologic mechanisms of recurrence. Methods: We reviewed 7 cases of recurrent choroidal melanoma following I-125 plaque brachytherapy managed with enucleation. Clinical characteristics included tumor dimensions, radiation dose, time to local recurrence, and clinical pattern of recurrence. Histopathology (hematoxylin and eosin and periodic acid – Schiff) and immunohistochemistry (Ki-67, CD-163, HMB45, and SOX10) were performed. Results: Mean follow-up time and time to local recurrence were 42 and 21 months after brachytherapy, respectively. Tumor recurrences were described clinically as marginal in 43%, diffuse in 29%, and extraocular extension (EOE) in 29%. Eighty-six percent were classified as mixed cell type and 14% were epithelioid type. Tumor zonation (histologic demarcation between zones of recurrent and nonrecurrent tumor cells by immunohistochemistry) was present in marginal and EOE cases (n = 6) and absent in the diffuse cases (n = 2). Ki-67 proliferative index was higher in marginal and EOE recurrences, while diffuse cases showed uniform ­Ki-67 staining. CD-163 staining was found to be greater in nonrecurrent tumor. HMB45 correlated with SOX10 with a greater staining in recurrent tumor. Conclusion: Our observations provide a correlation between histopathologic and clinical patterns of local recurrence of choroidal melanoma after brachytherapy.

Half-life of alpha-fetoprotein in neonatal sacrococcygeal teratoma

BackgroundAlpha-fetoprotein (AFP) is useful as a tumor marker for sacrococcygeal teratoma (SCT). We investigated the half-life of AFP in SCT. MethodsNeonates who underwent surgical treatment for SCT between 1997 and 2016 were included in the study, whereas patients who died before or after surgery or had malignant germ cell tumors were excluded. ResultsFifty-five non-recurrent SCT patients (M:F = 18:37) were enrolled. They underwent surgery on average 7.4 ± 4.1 days after birth. Serum AFP was measured an average 4.25 ± 2.07 times per patient. We obtained 165 half-lives following the formula (M = Mo * (1/2) Δt/T). A positive correlation was observed between half-life and patient age using the formula T1/2 = 0.0597 × days +6.1643 (p < 0.001). It was different from recurrent SCT (T1/2 = 0.1196 × days −0.0633) (p < 0.05). Half-life was different between mature SCT (T1/2 = 0.0671 × days +4.3912) and immature SCT (T1/2 = 0.0433 × days +8.9339) (p < 0.05). ConclusionThe half-life of AFP in neonatal patients with SCT was prolonged in proportion to the age, and it was getting longer in recurrent tumor than non-recurrent tumor. The half-life of AFP was longer in immature teratoma than in mature teratoma. Level of EvidenceIV.

HumanMethylation450K Array-Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer.

Background:High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management.Patients and methods:A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing.Results:Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values.Conclusions:This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

Preoperative airway management and perioperative period asphyxia prevention in patients with tumors invasion in the cervical tracheal

Objective:To investigate the effect of preoperative airway treatment and postoperative asphyxiation preventive measures in patients with tumors invasion in the cervical tracheal. Method:The clinical date of 35 patients with different degree of tumors invasion in the cervical tracheal were analyzed retrospectively. Anesthesia including normal endotracheal intubation anesthesia, awake intubation anesthesia with visual laryngoscope assisted after topical anesthesia, intubation anesthesia with preoperative tracheotomy, intubation anesthesia after transection of trachea and anesthesia with extracoporeal circulation was selected according to the patient's situation such as whether exist forced position, or the extent of dyspnea, or the range of recurrent tumor. Preventive tracheotomy or fistulization was performed according to the patients' tracheal involvement and the choice of operation and general condition during the operation. Result:All 35 patients were successfully anesthetized, 17 of whom had no dyspnea or forced position, this kind patients were all anesthesia successfully, and 3 of them underwent prophylactic tracheotomy. Sixteen cases of nonrecurrent tumor with forced position, 15 patients were accepted awake anesthesia successfully with visual laryngoscope assisted after topical anesthesia, 1 patient who cannot be intubated or done tracheotomy is completed with extracorporeal circulation; prophylactic tracheotomy or tracheostomy was performed in this group. Of 2 cases of recurrent tumor with forced posture, preoperative tracheal intubation failed, 1 case was intubated after emergency transection of trachea, 1 case was successfully intubated by emergency tracheotomy before operation and 2 cases received postoperative tracheostomy. In this study, no serious complications such as massive bleeding, asphyxia and cardiovascular accident occurred after the operation. Conclusion:The preoperative airway management of patients whose tumors involves the cervical tracheal and whether tracheotomy or ostomy need to prevent asphyxia or not should be based on the nature of the tumor such as whether is recurrent, the extent of trachea involvement and whether to merge the OSAHS. Only by considering the various factors that affect the airway synthetically, an effective method can be adopted to ensure the safety of the operation.

Study on the correlation between high expression of Gli1 protein and recurrence and metastasis of colorectal cancer

Objective To investigate the expression of Gli1 protein in colorectal cancer (CRC) tissues, and evaluate its association with the prognoses of the patients. Methods A total of 106 patients were enrolled and their clinicopathological characteristics were analyzed. The expression of Gli1 proteins were detected by immunohistochemical staining, and its association with time to recurrence/metastasis (TTR) and overall survival (OS) of the patients were analyzed. Results The positive rate and expression intensity of Gli1 protein in recurrent or metastatic tumor tissues were higher than those in non-recurrent and non-metastatic tumor tissues [86.84% (33/38) vs. 58.82% (40/68), 1.32 scores vs. 0.71 scores, both P 0.05). The positive rates and expression intensities of Gli1 and Ki-67 proteins in CRC tissues were higher than those in adjacent tissues [26.42% (28/106) and 0.27 scores; 4.72%(5/106), 0.05 scores] and normal tissues [3.33% (1/106), 0.03 scores; 0, 0.00 scores] (all P < 0.01). Results of univariate analysis showed that the expression of Gli1 protein, tumor grade and lymph node involvement were significantly associated with TTR, but all of the clinicopathological factors had no obvious association with OS. The association remained significant between the expression of Gli1 protein and TTR in multivariate analysis(P < 0.01). Conclusion The expression of Gli1 protein is an independent prognostic marker of recurrence or metastasis in CRC patients, its high expression implicates a high risk of CRC recurrence or metastasis. Key words: Colorectal neoplasms; Recurrence; Metastasis; Protein, Gli1

MiR-1, a Potential Predictive Biomarker for Recurrence in Prostate Cancer After Radical Prostatectomy

BackgroundIncreasing evidence suggests that aberrant microRNAs expressions are significantly associated with cancer progression. Previous studies have reported that the relative expression of miR-1 is significantly downregulated in recurrent prostate cancer (PCa) samples when compared with nonrecurrent PCa tissues. However, whether miR-1 can serve as a novel predictive biomarker for PCa recurrence still remains unclear. Materials and MethodsThe patients with clinically localized PCa who underwent radical prostatectomy by the same medical team at the Department of Urology, Ningbo No.2 Hospital were enrolled in this study. We examined the miR-1 expression levels in recurrent and nonrecurrent tumor samples by quantitative reverse transcription polymerase chain reaction. Univariate and multivariate Cox proportional hazards analyses were used for the evaluation of potential predictors of PCa recurrence. ResultsDuring the study period, 78 patients (including 27 in the recurrent group and 51 in the nonrecurrent group) who were diagnosed with PCa and who underwent radical prostatectomy were included in the final analysis. MiR-1 was significantly downregulated in recurrent PCa tissues when compared with nonrecurrent tumor samples (P < 0.001). The univariate and multivariate Cox proportional hazards analyses indicated that miR-1 was the only independent prognostic factor for PCa recurrence (hazard ratio = 1.86; 95% CI: 1.21-2.94; P = 0.011). The area under the curve value of miR-1 for PCa recurrence was 0.885 (P < 0.001) with the sensitivity of 0.863 and specificity of 0.889 based on receiver operating characteristic curve analysis. ConclusionsThis study identifies that miR-1 in PCa tissues can function as an important independent predictive factor for PCa recurrence.

Utilisation of antibody microarrays for the selection of specific and informative antibodies from recombinant library binders of unknown quality

Many diagnostic and therapeutic concepts require antibodies of high specificity. Recombinant binder libraries and related selection approaches allow the efficient isolation of antibodies against almost every target of interest. Nevertheless, it cannot be guaranteed that selected antibodies perform well and interact specifically enough with analytes unless an elaborate characterisation is performed. Here, we present an approach to shorten this process by combining the selection of suitable antibodies with the identification of informative target molecules by means of antibody microarrays, thereby reducing the effort of antibody characterisation by concentrating on relevant molecules. In a pilot scheme, a library of 456 single-chain variable fragment (scFv) binders to 134 antigens was used. They were arranged in a microarray format and incubated with the protein content of clinical tissue samples isolated from pancreatic ductal adenocarcinoma and healthy pancreas, as well as recurrent and non-recurrent bladder tumours. We observed significant variation in the expression of the E3 ubiquitin-protein ligase (CHFR) as well as the glutamate receptor interacting protein 2 (GRIP2), for example, always with more than one of the scFvs binding to these targets. Only the relevant antibodies were then characterised further on antigen microarrays and by surface plasmon resonance experiments so as to select the most specific and highest affinity antibodies. These binders were in turn used to confirm a microarray result by immunohistochemistry analysis.

Methylation of HOXA9 and ISL1 Predicts Patient Outcome in High-Grade Non-Invasive Bladder Cancer.

IntroductionInappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis.MethodsPromoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases.ResultsThe ISL1 genes’ promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008). ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively). Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%), and was associated with disease-specific mortality (DSM).ConclusionsIn this study we report methylation differences and similarities between clinical sub-types of high-grade NMIBC. We report the potential ability of methylation biomarkers, at initial diagnosis, to predict tumour recurrence and progression within one year of diagnosis. We found that specific biomarkers reliably predict disease outcome and therefore may help guide patient treatment despite the unpredictable clinical course and heterogeneity of high-grade NMIBC. Further investigation is required, including validation in a larger patient cohort, to confirm the clinical utility of methylation biomarkers in high-grade NMIBC.

Oil Machinery Fluid of Craniopharyngioma. Biochemical Analysis: Clinico-Pathological Correlation

Craniopharyngiomas are histologically benign tumors, but they have a tendency to become adherent around the pituitary gland and pituitary stalk, including the optic nerves, optic chiasm, intracranial arteries and the brain itself. 15 cases of craniopharyngiomas were included in this study. The oil fluid biochemical analysis was made; glucose, cholesterol, lipids, proteins, lactate dehydrogenase, globulins, calcium, sodium, etc. and Western Blot was performed for 2 and 9 metalloproteins. Clinicopatological correlation was made. Groups were divided in recurrent and non-recurrent tumor. The age of patient ranged from 18 to 51 yr 11 (mean of 30yrs). 11 (73%) were females and 4 (27%) were male. Recurrence was in 8 (53%) cases. We analyze the mean of laboratory results obtaining normal to low serum values for ions and high fluid values for all the elements studied. There was no statically significance between them, but we observe the patients which had a big tumor, recurrence and green color oil fluid presented high levels of these components. By the other hand, little not recurrent tumors and with a yellow oil fluid aspect, had low serum values of alkaline phosphatase, serum glutamic oxaloacetic and glutamic-pyruvic transaminases. The output of these components in the Central Nervous System can be toxic and produce more inflammatory response.

Abstract 291: Genomewide scale epigenetic profile and prostate cancer recurrence

Abstract Development and progression of prostate cancer reflect the accumulation of genetic and epigenetic alterations. Although genetic changes are involved in the inactivation of genes with important anti-cancer functions, DNA methylation in a promoter region is an important epigenetic mechanism for the down-regulation (silencing) of expression of these genes. Therefore, we conducted a genome-wide profile of prostate tumors to identify epigenetically altered regions that distinguish recurrent from non-recurrent cases. We profiled the epigenetic landscape of 125 prostate tumors using bisulfite treated tumor DNA samples extracted from 65 recurrent and 60 non-recurrent prostate cancer cases. Epigenome-wide methylation analysis was performed at the Molecular Genomic Core Facility of the Moffitt Cancer Center using Illumina Infinium Human Methylation 450K Beadchip, which can quantitatively measure over 485,577 CpG sites with 99% coverage of RefSeq Gene and 96% coverage of CpG islands. For methylation data analysis, intensities were normalized using Illumina GenomeStudio software. Beta values with assigned detection p-values &amp;gt; 0.01 were treated as missing data. We considered the methylation pattern at a larger region instead of methylation at single sites. Thus, in addition to evaluating methylation at single sites, we were interested in the number of significantly differently methylated probes within a gene as a measure of how significant a gene is. We identified 269 differentially methylated CpG sites between recurrent and non-recurrent tumor tissues, with a false discovery rate (FDR) q-value less than 0.05 and a mean methylation difference greater than 0.1 between the two groups (recurrent /non-recurrent cases). Eleven genes where more than 25% of the measured positions were differently methylated (p&amp;lt;0.05 and &amp;gt;0.1 between the medians of the two groups) between recurrent and non-recurrent samples. We further investigated ALEX1 (ARMCX1), which is one of the 11 genes and suggested as a tumor suppressor gene. ALEX1 (Arm protein lost in epithelial cancers, on chromosome X) is involved in a variety of processes such as cell adhesion, embryogenesis and tumorigenesis. Expression of ALEX1 mRNA is significantly reduced in various tumor tissues, including prostate carcinomas and in various cancer cell lines. We investigated expression level of ALEX1 in an additional 392 prostate tumor samples (145 recurrence and 247non-recurrent) using realtime RT-PCR. Based upon average Ct ratios between ALEX1 and β actin, ALEX1 is down regulated 2.67 fold in tumor tissues from recurrent cases as compared with non-recurrent cases (p&amp;lt;0.001). If replicated, these identified biomarkers may be used at the time of diagnosis to predict risk of recurrence and improve clinical treatment decision-making. Citation Format: Hui-Yi Lin, Anders Berglund, Thomas Sellers, Ardeshir Hakam, Hyun Park, Julio Pow-Sang, Jong Y. Park. Genomewide scale epigenetic profile and prostate cancer recurrence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 291. doi:10.1158/1538-7445.AM2014-291

MiR-1 and miR-133b are differentially expressed in patients with recurrent prostate cancer.

Prostate cancer (PCa) is currently the most frequently diagnosed malignancy in the western countries. It is more prevalent in older men with 75% of the incident cases above 65 years old. After radical prostatectomy, approximately 30% of men develop clinical recurrence with elevated serum prostate-specific antigen levels. Therefore, it is important to unravel the molecular mechanisms underlying PCa progression to develop novel diagnostic/therapeutic approaches. In this study, it is aimed to compare the microRNA (miRNA) profile of recurrent and non-recurrent prostate tumor tissues to explore the possible involvement of miRNAs in PCa progression. Total RNA from 41 recurrent and 41 non-recurrent PCa tissue samples were used to investigate the miRNA signature in PCa specimens. First of all, 20 recurrent and 20 non-recurrent PCa samples were profiled using miRNA microarray chips. Of the differentially expressed miRNAs, miR-1, miR-133b and miR-145* were selected for further validation with qRT-PCR in a different set of 21 recurrent and 21 non-recurrent PCa samples. Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic analysis. Our results demonstrated that miR-1 and mir-133b have been significantly downregulated in recurrent PCa specimens in comparison to non-recurrent PCa samples and have sufficient power to distinguish recurrent specimens from non-recurrent ones on their own. Here, we report that the relative expression of miR-1 and mir-133b have been significantly reduced in recurrent PCa specimens in comparison to non-recurrent PCa samples, which can serve as novel biomarkers for prediction of PCa progression.

Role of progesterone receptor expression and proliferative activity in predicting the recurrence of meningioma

Introduction A putative role for progesterone in the growth of meningioma has been suggested. The aim of this study was to attest the role of progesterone receptor (PR) in predicting the biological behavior of meningioma. Material and methods The study included 30 cases of meningioma, 15 (50%) recurrent and 15 (50%) non-recurrent. The immunohistochemical expression of PR was studied. Cell kinetic using the Ki67/MIB-1 labelling index (LI) was evaluated and correlated to PR expression. Results PR expression was significantly more common in benign meningioma (BM) than atypical meningioma (AM) and malignant meningioma (MM). The mean Ki-67/MIB-1 LI was significantly highest in MM, high in AM and lowest in BM. In PR-negative meningioma, the mean Ki-67/MIB-1 LI was significantly higher compared with PR-positive meningioma. In the recurrent group, PR was frequently immunonegative and the mean Ki-67/MIB-1 LI was higher than that in the non-recurrent group. The difference in PR expression between non-recurrent and recurrent cases was significant only in BM. The difference in Ki-67/ MIB-1 LI was significant only when recurrent meningioma was compared with non-recurrent tumor, irrespective of the grade. Conclusion BM expresses PR more than AM and MM. The absence of this expression in BM implies a likely risk for recurrence. Ki-67/MIB-1 LI is valuable to predict tumor grade and the overall risk of recurrence. However, it must be interpreted with caution in BM.

Role of progesterone receptor expression and proliferative activity in predicting the recurrence of meningioma

Introduction A putative role for progesterone in the growth of meningioma has been suggested. The aim of this study was to attest the role of progesterone receptor (PR) in predicting the biological behavior of meningioma. Material and methods The study included 30 cases of meningioma, 15 (50%) recurrent and 15 (50%) non-recurrent. The immunohistochemical expression of PR was studied. Cell kinetic using the Ki67/MIB-1 labelling index (LI) was evaluated and correlated to PR expression. Results PR expression was significantly more common in benign meningioma (BM) than atypical meningioma (AM) and malignant meningioma (MM). The mean Ki-67/MIB-1 LI was significantly highest in MM, high in AM and lowest in BM. In PR-negative meningioma, the mean Ki-67/MIB-1 LI was significantly higher compared with PR-positive meningioma. In the recurrent group, PR was frequently immunonegative and the mean Ki-67/MIB-1 LI was higher than that in the non-recurrent group. The difference in PR expression between non-recurrent and recurrent cases was significant only in BM. The difference in Ki-67/ MIB-1 LI was significant only when recurrent meningioma was compared with non-recurrent tumor, irrespective of the grade. Conclusion BM expresses PR more than AM and MM. The absence of this expression in BM implies a likely risk for recurrence. Ki-67/MIB-1 LI is valuable to predict tumor grade and the overall risk of recurrence. However, it must be interpreted with caution in BM.