Histopathologic Tumor Grade Research Articles

A Study of Ki 67 Immunostaining in Prostate Carcinomas: Correlation with Gleason’s Score

Background: One of the most common causes of carcinoma deaths among men is prostate cancer. In view of the above, early diagnosis and effective treatment of the disease are immensely important. The increasing number of options for the treatment of prostate cancer has made the prognostic evaluation of the disease even more important. Proliferation plays an important role in the clinical behaviour of prostate cancer. Ki-67 binding, is an objective measurement of cell proliferation which significantly aids in the management of the prostate patients. Gleason grading describes the aggressiveness of prostate cancer. The Objectives was to study the immunostaining patterns of Ki-67 in prostate cancers and to compare the results with Gleason's score. Methods: Fifty cases of histopathologically proven prostate carcinomas diagnosed on needle biopsies and transurethral resection specimens was studied in JSS medical college and hospital, mysore for a period of 3years and histopathological grade was assessed using Gleason grading system. Immunohistochemistry (IHC) for Ki-67 was done on paraffin embedded wax sections. Result: Ki-67 was positive in 49/50 cases (98%). The range of Ki-67 score was 0 to 94%. No statistically significant association was seen with Ki-67 and gleasons scores (P=0.277). Conclusion: Proliferation has been recognized as a distinct hallmark of cancer and acts as an important determinant of cancer outcome. As Ki-67 can be used to objectively measure this, it can be included in the pool of prognostic markers like tumor volume, histopathological grade and surgical margins.

Monoamine Oxidase B in Renal Cell Carcinoma.

BackgroundStudies on monoamine oxidase B (MAO-B) expression in renal cell carcinoma (RCC) are lacking. This study focused on the immunohistochemical evaluation of MAO-B in RCC.Material/MethodsSixty-three RCC samples were compared on basic clinical and histopathological parameters, including histopathological type and tumor grade. RCC samples were divided according to the histopathological type into 2 groups: conventional type (51 samples) and other types (12 samples). For MAO-B detection, a standard immunohistochemical procedure was employed.ResultsIn healthy kidney samples, MAO-B was detected predominantly in tubules. Fifty-two cancer tissue samples were MAO-B negative and 11 tissue samples were MAO-B low positive. Enzymes were detected only in the cytoplasm. We did not find any significant correlation between the percentage of positive MAO-B specimens and nuclear grade. Additionally, Fisher’s test did not reveal any difference in numbers of positive and negative MAO-B samples between the 2 RCC types (P>0.05).ConclusionsFrom our results, it was clear that MAO-B expression played no significant role in stimulation of renal cancer development. We found that MAO-B occurred only in 19% of kidney tumors and that the positivity of protein expression was low. Moreover, it seems that the disappearance of this enzyme in RCC is a consequence of replacement of healthy tissue by cancer cells. On the other hand, one can assume that the loss of MAO-B expression could be associated with severe pathological processes in the kidney.

Radiomics analysis of apparent diffusion coefficient in cervical cancer: A preliminary study on histological grade evaluation.

The role of apparent diffusion coefficient (ADC)-based radiomics features in evaluating histopathological grade of cervical cancer is unresolved. To determine if there is a difference between radiomics features derived from center-slice 2D versus whole-tumor volumetric 3D for ADC measurements in patients with cervical cancer regarding tumor histopathological grade, and systematically assess the impact of the b value on radiomics analysis in ADC quantifications. Prospective. In all, 160 patients with histopathologically confirmed squamous cell carcinoma of uterine cervix. Conventional and diffusion-weighted MR images (b values = 0, 800, 1000 s/mm2 ) were acquired on a 3.0T MR scanner. Regions of interest (ROIs) were drawn manually along the margin of tumor on each slice, and then the center slice of the tumor was selected with naked eyes in the course of whole-tumor segmentation. A total of 624 radiomics features were derived from T2 -weighted images and ADC maps. We randomly selected 50 cases and did the reproducibility analysis. Parameters were compared using Wilcoxon signed rank test, Bland-Altman analysis, t-test, and least absolute shrinkage and selection operator (LASSO) regression with crossvalidation. In all, 95 radiomics features were insensitive to ROI variation among T2 images, ADC map of b800, and ADC map of b1000 (P > 0.0002). There was a significant statistical difference between the performances of 2D center-slice and 3D whole-tumor radiomics models in both ADC feature sets of b800 and b1000 (P < 0.0001, P < 0.0001). Compared with ADC features of b800 (0.3758 ± 0.0118), the model of b1000 ADC features appeared to be slightly lower in overall misclassification error (0.3642 ± 0.0162) (P = 0.0076). Several radiomics features extracted from T2 images and ADC maps were highly reproducible. Whole-tumor volumetric 3D radiomics analysis had a better performance than using the 2D center-slice of tumor in stratifying the histological grade of cervical cancer. A b value of 1000 s/mm2 is suggested as the optimal parameter in pelvic DWI scans. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:280-290.

Apparent diffusion coefficient of hepatocellular carcinoma on diffusion-weighted imaging: Histopathologic tumor grade versus arterial vascularity during dynamic magnetic resonance imaging.

ObjectivesApparent diffusion coefficient (ADC) has been suggested to reflect the tumor grades of hepatocellular carcinomas (HCCs); i.e., it can be used as a biomarker to predict the patients’ prognosis. To verify its feasibility as a biomarker, the present study sought to determine how the ADC values of HCC are affected by a tumor’s histopathologic grade and arterial vascularity.Materials and methodsFrom 131 consecutive patients, 141 surgically resected HCCs (16 well-differentiated [wd-HCCs], 83 moderately-differentiated [md-HCCs], and 42 poorly-differentiated HCCs [pd-HCCs]) were subjected to a comparison of the tumors’ arterial vascularity (non-, slightly-, or markedly-hypervascular) determined on dynamic magnetic resonance imaging (MRI) and the ADC was measured retrospectively.ResultsThe pd-HCCs (1.05±0.16 × 10−3 mm2/s) had a significantly lower ADC than md-HCCs (1.16±0.21 × 10−3 mm2/s; p = 0.010), but there was no significant difference compared to wd-HCCs (1.11±0.18 × 10−3 mm2/s; p = 0.968). The mean ADC was significantly higher in markedly hypervascular lesions (1.20±0.20 × 10−3 mm2/s) than in nonhypervascular lesions (0.95±0.14 × 10−3mm2/s; p<0.001) or slightly hypervascular lesions (1.04±0.15 × 10−3mm2/s; p<0.001). The ADC values and arterial vascularity were significantly correlated in wd-HCCs (p = 0.005) and md-HCCs (p<0.001). The mean ADC of pd-HCCs was significantly lower than those of other lesions, even in the markedly hypervascular lesion subgroup (p = 0.020).ConclusionAlthough pd-HCC constantly shows low ADCs regardless of arterial vascularities, ADCs cannot stably stratify histopathologic tumor grades due to the variable features of wd-HCCs; and the ADC should be used with caution as a tumor biomarker of HCC.

Assessment of Histopathological Grade and Ki-67 Expression in Tobacco and Non-tobacco Habitual Buccal Mucosa Cancer

Although there are various risk factors in the literature, the established primary risk factor for oral cancer is tobacco and betal-nut chewing habits. It is believed that pathogenesis of oral cancer depends on the aetiology. To assess the histopathological grade and Ki-67 expression in tobacco (smoking/smokeless) and non-tobacco (betal nut/pan masala) habitual buccal mucosa cancer. The cross-sectional study was carried out in Regional cancer centre, Tamilnadu. Proliferative marker, Ki-67 expression was determined by immunohistochemistry using biotin-streptavidin method. The study includes 117 buccal mucosa cancer patients (61 male and 56 female). According to WHO grading system, high frequency observed with well differentiated squamous cell carcinoma 48 (41%) followed by moderate 46 (39.3%) and poorly differentiated 23 (19.7%). The cut-off value 50% was used to categorize Ki-67 expression into low and high labelling index (LI); 96 (82%) buccal mucosa cancer and 4 (3.4%) adjacent normal mucosa patients showed high Ki-67 expression. The present study showed highly significant association of histopathological tumor grade and Ki-67 expression by Chi square and paired t test p < 0.05. All the patients were grouped as tobacco 87 (74.4%) and non-tobacco habitual 30 (25.6%) in 3:1, respectively. Further, the risk habits identified with significant differences of tumor grade (p = 0.028) and Ki-67 at p < 0.05. Thus, the study revealed that the nature of cell differentiation and proliferation was strongly related to consumption of carcinogen in both tobacco and non-tobacco form. Therefore, histopathological grade and Ki-67 could be used as a reliable biomarker to understand the biological behaviour of risk habits which might helpful for further treatment therapeutics.

Correlation of Gankyrin oncoprotein overexpression with histopathological grade in prostate cancer.

Prostate cancer is the second most commonly diagnosed cancer among men worldwide. Identifying new prognostic and predictive biomarkers will help stratification of prostate cancer patients for a better treatment. Gankyrin is a novel oncoprotein which regulates cell cycle and protein degradation. Gankyrin overexpression correlated with the malignant phenotypes and promotes the tumorigenicity and metastasis in many cancers. However, there are not any reports on the role of Gankyrin in prostate cancer. Therefore, this study was designed to investigate the expression of Gankyrin in prostate cancer and analyze its correlation with some clinicopathological characteristics. We characterized the expression of gankyrin in fifty five prostate cancer specimens and twenty non-cancerous tissues by immunohistochemical staining and the results were correlated with clinical characteristics and pathological parameters.Results showed that Gankyrin was expressed in 41 of 55 (74%) prostate cancer patients and its expression was significantly higher than corresponding adjacent normal tissues (p<0.001). Gankyrin overexpression was significantly correlated with histopathological tumor grade, Gleason score and tumor differentiation (P=0.002). These findings showed that Gankyrin is mainly overexpressed in high grade prostate tumors so it may have a significant role in prostate cancer progress and it May serve as a useful biomarker for the identification of aggressive prostate cancers.

Analysis of SHIP2 Expression and its Correlation with VEGF and HER-2 Expression in Breast Cancer

Purpose: To investigate SHIP2 expression in breast cancer tissues, and its correlation with clinicopathological features and with the expressions of VEGF and HER-2 in cancer tissues. Methods: Immunohistochemical staining for SHIP2, HER-2 and VEGF was performed on paraffin-embedded tissue specimens, including 80 specimens of breast cancer and 53 adjacent tissue samples. Two pathologists were invited to interpret the immunohistochemistry results using double-blind method. Expression profiles of SHIP2, HER-2 and VEGF were evaluated and scored according to percentage of positive cells and positive signal intensity. The correlation between SHIP2 and clinicopathological features was analyzed by chi-square test and fourfold table exact test. The correlation among SHIP2, HER-2 and VEGF expression were analyzed using Pearson contingency coefficient analysis for evaluating prognostic relevance to breast cancer. Results: The positive expression rates of SHIP2, HER-2 and VEGF were significantly higher than that of adjacent normal tissues (p<0.05). SHIP2 expression was significantly increased, in the case of the four risk factors (the poor histological grade, the later stages, lymph node metastasis, and higher BMI) (p<0.05). Positive rate of both SHIP2 and VEGF protein expression indicated a significant correlation between the two proteins (r=0.30, p<0.05). In addition, in the HER-2 protein positive group, SHIP2 protein expression also showed a positive correlation (r=0.71, p<0.05) between these two proteins. Expression of all three proteins were highly related to tumor histopathologic grade, clinical terms, and lymphatic metastasis (p<0.05). Our data indicates that SHIP2 expression in tumor tissue is significantly correlated with HER-2 and VEGF expression. Conclusion: Our study provides a proof of concept that SHIP2, correlated with HER-2 and VEGF, plays important roles in tumorigenesis, infiltration, and metastasis of breast cancer, and are highly associated with prognosis.

The relationship between histological differentiation and disease recurrence of primary oral squamous cell carcinoma.

Background:Although advance techniques were available for diagnosis and prognosis of oral cancer, histopathology was used as major method in clinical routine. Of all oral subsites, buccal mucosa squamous cell carcinoma is aggressive in nature with poor survival. Therefore, the aim of the present study was to evaluate the relation of tumor histopathological grade with disease recurrence of buccal squamous cell mucosa carcinoma.Materials and Methods:A retrospective study was carried out in regional cancer research institute, Tamil Nadu. Demographic, histopathological and participant's follow-up details were collected from medical records.Results:Of 198 participants, high frequently encountered with well-differentiated squamous cell carcinoma (n = 98, 49.5%). The clinical characteristics of lymphovascular invasion (P = 0.031), perineural invasion (P = 0.019), tumor stage (P = 0.004), tumor depth (P = 0.048), lymph node (P = 0.02) and metastasis (P = 0.043) had significant association with histopathological grade. In addition, the treatment strategies (P = 0.014) also showed significance at P < 0.05. Further, multivariate revealed cell differentiation (P = 0.048), tumor size (P = 0.037) and depth (P = 0.021) as independent hazard risk of the development of disease using recurrence-free survival of participants at P < 0.05. Of 198 participants, 24 (12.1%) recurrences reported during 34-month follow-up period and the overall estimated recurrence-free survival was 52%. The high frequency of recurrence, 12 (50%), was identified with moderately differentiated tumor cells. However, poorly differentiated tumor showed significantly lower survival (28%) than moderate (54%) and well differentiated (81%) by Kaplan–Meier analysis using log-rank test (P = 0.004, P < 0.05).Conclusions:The present study concludes high frequency of recurrence observed in moderately differentiated and also revealed lower survival in poorly differentiated tumor. Hence, further treatment plans should focus on moderate and poorly differentiated tumors to improve survival outcome.

Pathologic stratification of operable lung adenocarcinoma using radiomics features extracted from dual energy CT images.

PurposeTo evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment.ResultsPathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i-uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514–1), 0.8610 (95% CI: 0.7547–0.9672), and 0.8394 (95% CI: 0.7045–0.9743), respectively.Materials and MethodsA total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades.ConclusionsQuantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma.

In the literature: October 2016

A consortium on clinical and molecular stratification on oesophageal adenocarcinoma established in Britain has recently published in Nature Genetics , a whole-genomic sequencing analysis of more than 100 samples.1 Interestingly, they describe three distinct molecular subtypes with potential treatment relevance. This observation has also been verified in an independent validation cohort. Those three types are: (1) the ones showing homologous recombination and chromosome segregation pathways defects with enrichment of a BRCA signature. These tumours would be sensitive to DNA damaging agents, including neutron and photon irradiation with the addition of PARP inhibitors, (2) a group with high mutational load and neoantigen burden, associated with an increased CD8+ T-cell density and with a dominant T>G mutational pattern, in which immunotherapy with anti-PD1 or PDL1 antibodies could have a role and (3) evidence of an ageing imprint with a C>A/T pattern and fewer unstable genomes and large duplication events, which may be sensitive to chemotherapy and antiHER2 or MET directed therapies. The clinical characteristics of the three subgroups did not differ significantly, implying that the classification, and hence spectrum of mutation patterns, does not vary with smoking, age, sex, tumour histopathological grade, tumour stage, response to chemotherapy, overall or recurrence-free survival, etc. Therefore, the mutation signature profiles seem to be …

Local image variance of 7 Tesla SWI is a new technique for preoperative characterization of diffusely infiltrating gliomas: correlation with tumour grade and IDH1 mutational status

ObjectivesTo investigate the value of local image variance (LIV) as a new technique for quantification of hypointense microvascular susceptibility-weighted imaging (SWI) structures at 7 Tesla for preoperative glioma characterization.MethodsAdult patients with neuroradiologically suspected diffusely infiltrating gliomas were prospectively recruited and 7 Tesla SWI was performed in addition to standard imaging. After tumour segmentation, quantification of intratumoural SWI hypointensities was conducted by the SWI-LIV technique. Following surgery, the histopathological tumour grade and isocitrate dehydrogenase 1 (IDH1)-R132H mutational status was determined and SWI-LIV values were compared between low-grade gliomas (LGG) and high-grade gliomas (HGG), IDH1-R132H negative and positive tumours, as well as gliomas with significant and non-significant contrast-enhancement (CE) on MRI.ResultsIn 30 patients, 9 LGG and 21 HGG were diagnosed. The calculation of SWI-LIV values was feasible in all tumours. Significantly higher mean SWI-LIV values were found in HGG compared to LGG (92.7 versus 30.8; p < 0.0001), IDH1-R132H negative compared to IDH1-R132H positive gliomas (109.9 versus 38.3; p < 0.0001) and tumours with significant CE compared to non-significant CE (120.1 versus 39.0; p < 0.0001).ConclusionsOur data indicate that 7 Tesla SWI-LIV might improve preoperative characterization of diffusely infiltrating gliomas and thus optimize patient management by quantification of hypointense microvascular structures.Key Points• 7 Tesla local image variance helps to quantify hypointense susceptibility-weighted imaging structures.• SWI-LIV is significantly increased in high-grade and IDH1-R132H negative gliomas.• SWI-LIV is a promising technique for improved preoperative glioma characterization.• Preoperative management of diffusely infiltrating gliomas will be optimized.

Neuroendocrine liver metastases: Value of apparent diffusion coefficient and enhancement ratios for characterization of histopathologic grade.

To assess the value of apparent diffusion coefficient (ADC) measured with diffusion-weighted imaging (DWI) and enhancement ratios (ER) measured with contrast-enhanced T1-weighted imaging (CE-T1WI) for the characterization of histopathologic tumor grade of neuroendocrine tumor liver metastases (NETLM). Twenty-two patients with pathology-proven NETLM and pretreatment 1.5 Tesla (T) and 3T MRI including DWI were included in this Institutional Review Board-approved retrospective study. ADC histogram parameters, including mean, minimum (min), skewness, and kurtosis as well as ER, were computed for all lesions. Tumor grading was based on the World Health Organization 2010 classification. Kruskal-Wallis and Mann-Whitney test were used to assess for differences in ADC and ER between different tumor grades. MRI parameters were correlated with pathologic findings using Spearman correlation test. Receiver operating characteristic analysis was performed to determine optimum thresholds for predicting tumor grade. Forty-eight NETLM (mean size 3.5 cm) were analyzed with the following grade distribution: G1 (n = 25), G2 (n = 16), and G3 (n = 7). ADC-mean (×10-3 mm2 /s) of G3 tumors (0.87 ± 0.43) was significantly lower than that of G1 (1.47 ± 0.63) and G2 (1.27 ± 0.63; P = 0.042). A weak significant negative correlation was observed between ADC and tumor grade (ADC-mean: r = -0.33, P = 0.02; ADC-min: r = -0.37, P = 0.01) and Ki-67 (ADC-mean: r = -0.31, P = 0.03; ADC-min: r = -0.39, P = 0.007). AUROC, sensitivity and specificity of ADC-mean/ADC-min/ER (measured at the early arterial phase) for differentiation of G3 versus G1-G2 were 0.80/0.76/0.67, 100%/50%/70%, and 68.4%/84.2%/66.6%, respectively. ADC is a promising marker for characterization of histopathologic grade of NETLM. These results should be confirmed in a prospective study. J. Magn. Reson. Imaging 2016;44:1432-1441.

Aldehyde dehyderogenase (ALDH1A1) delineating the normal and cancer stem cells in spectral lung lesions: An immunohistochemical appraisal

Background and aimALDH1A1 is one of the promising cancer stem cell markers, it has been found in different cancers, including lung cancer. We aimed to assess its immunohistochemical expression in spectral lung lesions (neoplastic versus non neoplastic) and to correlate its expression with certain pathological parameters (e.g. histopathological type and tumor grade). Materials and methodsThe study included 105 specimens of spectral lung lesions (20 adjacent normal tissues, 64 non small cell carcinoma (NSCLCs), 16 small cell carcinoma (SCLCs) and six inflammatory pseudotumors, in addition to nine metastatic tumors to lymph nodes. Both H&E and immunohistochemical stained sections were assessed and evaluated according to quick immunoreactivity score. ResultsALDH1A1 expression showed a broad dynamic range of immunoreactivity score (0–8) in different types of lung cancers with strong reactivity of normal stem cells. Significant statistical associations were found between ALDH1A1 expression and squamous cell carcinoma & SCLC (p=0.02 and 0.003, respectively), with very high mean percentage of positive cells in SCLC (58.50±10.62), followed by adenocarcinoma and squamous cell carcinoma (38.37±35.12 and 22.77±13.89, respectively). Adenocarcinomas were classified according to the IASLC/ATS/ERS classification and grouped by architectural grade into low, intermediate and high. Heterogeneity of ALDH1A1 immunoreactivity scores within adenocarcinoma can reflect histological patterns heterogeneity with a strong association to the grade. Strong diffuse expression was seen in inflammatory pseudotumors and impressive membranous expression was noticed in metastatic tumors. Important pitfalls of ALDH1A1 immunostaining were applied for accurate interpretations. ConclusionWe ascertained the presence of strong association between ALDH1A1 expression and both histological subtype & tumor grade of NSCLCs. We report a fascinating finding; ALDH1A1 heterogeneity within adenocarcinoma can be mapped to its histological patterns. Furthermore, we elucidated its presence in SCLCs and inflammatory pseudotumors. Also a comparative image was drawn between its expressions in the primary lung tissue and in the metastatic lymph nodes.

Association between sonographic appearances of breast cancers and their histopathologic features and biomarkers.

The purpose of this study was to investigate potential associations between invasive breast cancer sonographic (US) findings and histopathologic patterns and biomarkers. One hundred consecutive women with invasive breast cancer treated in the Breast Diagnostic Center of Brotzu Hospital in Cagliari, Italy, from January to October 2013, were retrospectively evaluated. Two experienced breast radiologists independently evaluated hard copies of US examinations performed during the US-guided biopsy procedure. Tumor characteristics were assessed by using the BI-RADS US lexicon. For each patient, the results of histopathologic examination, tumor grading, hormone-receptor status, HER2, and Ki67 were considered. US characteristics were compared with histopathologic features and biomarkers. Statistical analysis was performed. Low-grade tumors were statistically significantly associated with spiculated margins (p = 0.002) and hyperechoic halos (p < 0.001). High-grade tumors were associated with abrupt interfaces, nonspiculated margins, and absence of posterior acoustic shadowing. Malignant breast masses with spiculated margins were significantly associated with hormone-receptor positivity (p = 0.009). The most frequent tumor grade was G3 in the HER2 + and triple-negative subgroups. Patients with G3 tumors were significantly younger than those with G1 or G2 disease (51.3 ± 9.5 years versus 58.7 ± 12.6 years; p = 0.004). Histopathologic patterns and breast cancer biomarkers determine differences in US imaging that can guide radiologists in better understanding the development of breast cancer and its prognosis.

Clinical presentation in insulinoma predicts histopathological tumour characteristics.

Insulinomas are rare neuroendocrine tumours (NETs) of the pancreas, characterized clinically by neuroglycopenic symptoms during periods of substrate deficiency. The gold standard test for diagnosing an insulinoma is a 72-h fast. However, the prognostic value of parameters in the standardized 72-h fast on histopathological tumour criteria and clinical presentation has not been examined. In thirty-three patients diagnosed with an insulinoma records, and data were investigated retrospectively. Histopathological tumour characteristics, including staging, grading and size, were reviewed. Grading was performed using Ki-67 index. Cut-off values for classical grading (G(clas)) were set at G1(clas) ≤ 2%, G2(clas) 3-20% & G3(clas) >20% and for modified grading (G(mod)) at G1(mod) <5%, G2(mod) 5-20% & G3(mod) >20%. When G(mod) criteria were applied, the initial blood glucose was lower in GII/III(mod) patients compared to GI(mod) (2.8 ± 0.8 vs 3.8 ± 1.3 mmol/l; P = 0.046). Basal and end of fast levels of insulin (basal insulin 71 ± 61 vs 20 ± 16 mU/l; P < 0.001; end of fast insulin 77 ± 51 vs 21 ± 20 mU/l; P < 0.001) and c-peptide (basal c-peptide 5.4 ± 2.4 vs 2.7 ± 1.6 μg/l; P = 0.004; end of fast c-peptide 5.3 ± 2.4 vs 2.5 ± 1.4 μg/l; P = 0.001) were significantly higher in GII/III(mod) than in GI(mod). No differences between the groups were observed when G(clas) criteria were applied. Additionally, close correlations were observed between insulin concentration, Ki-67 index and tumour size. This study shows an impact of histopathological tumour characteristics in patients suffering from an insulinoma on clinical presentation during a standardized 72-h fast. Lower initial blood glucose levels and higher concentrations of insulin and c-peptide are associated with worse tumour grading and larger tumour size.

Significance of suppressor of cytokine signaling-3 expression in bladder urothelial carcinoma in relation to proinflammatory cytokines and tumor histopathological grading.

Bladder cancer is among the five most common malignancies worldwide. Altered expression of suppressor of cytokine signaling -3 (SOCS-3) has been implicated in various types of human cancers; however, its role in bladder cancer is not well established. The present study was undertaken to investigate the mRNA expression of SOCS-3 in normal and cancerous bladder tissue and to explore its correlation with urinary levels of some proinflammatory cytokines, cytokeratin-18 (CK -18) and with tumor histopathological grading, in order to evaluate their role as potential diagnostic markers. SOCS3 mRNA expression levels were evaluated using quantitative real time PCR. Urinary levels of interleukins 6 and 8 were estimated by enzyme linked immunosorbent assay (ELISA). Cytokeratin-18 expression was analyzed by immuunohistochemistry then validated by ELISA. SOC3 m RNA expression levels were significantly lower in high grade urothelial carcinoma (0.36±0.12) compared to low grade carcinoma (1.22±0.38) and controls (4.08±0.88), (p<0.001). However, in high grade urothelial carcinoma the urinary levels of IL-6, IL-8, total CK-18(221.33±22.84 pg/ml, 325.2±53.6 pg/ ml, 466.7±57.40 U/L respectively) were significantly higher than their levels in low grade carcinoma (58.6±18.6 pg/ ml, 58.3±50.2 pg/ml, 185.5±60.3 U/L respectively) and controls (50.9±23.0 pg/ml, 7.12±2.74 pg/ml, 106.7±47.3U/L respectively), (p<0.001). Advanced grade of urothelial bladder carcinoma is significantly associated with lowered mRNA expression of SOC3 as well as elevated urinary levels of proinflammatory cytokines and CK-18. Furthermore, our results suggested that urinary IL-8, IL-6 and CK-18 may benefit as noninvasive biomarkers for early detection as well as histopathological subtyping of urothelial carcinoma.

May the platelet to lymphocyte ratio be a prognostic factor for epithelial ovarian cancer?

The study aimed to evaluate changes in hematologic parameters, including white blood cell, platelet count, platelet indices, the platelet to lymphocyte and neutrophil to lymphocyte ratios in patients with early and advanced stages of epithelial ovarian cancers. The study included 100 patients with epithelial ovarian cancer who underwent primary staging exploratory laparotomy. Preoperative hematologic parameters, tumor histopathologic type, grade, stage and serum CA-125 levels were retrospectively analyzed. These parameters were compared between the patients with early (stage I-II) and advanced (stage III-IV) ovarian cancer. White blood cell count and platelet indices, including mean platelet volume, platelet distribution width and platelet crit did not show a statistically significant difference between groups with early and advanced ovarian cancer. However, the neutrophil to lymphocyte ratio, platelet count, the platelet to lymphocyte ratio and CA-125 level showed a statistically significant difference between the two groups (p<0.05, p<0.01, p<0.001, p<0.01 respectively). It was found that the neutrophil to lymphocyte ratio, platelet count and the platelet to lymphocyte ratio increased with the increasing stage of ovarian cancer. Furthermore, it was seen that the platelet to lymphocyte ratio is an independent prognostic factor related to the stage of epithelial ovarian cancer.

Relationship between BMI, PSA and Histopathological Tumor Grade in a Caucasian Population Affected by Prostate Cancer

The aim of this work is to show the relationship between obesity and aggressivenes of Prostate Cancer. We conducted a retrospective study of 132 men affected by Prostate Cancer underwent radical prostatectomy. Gleason score was abstracted by biopsy specimens and by post-operatory specimens. We evaluated PSA level and Body Mass Index (BMI).

Abstract 1244: Licofelone, a dual COX-LOX inhibitor prevents transitional cell carcinoma of urinary bladder in UPII-SV40T transgenic mice

Abstract Urinary bladder cancer is the sixth most commonly diagnosed cancer and significant proportion of the patients diagnosed with bladder cancer have high-grade tumors that are at potential risk for post-surgical recurrence and metastasis, where 5-year survival is very low. Hence it is important to identify and develop regimens that prevent urothelial tumorigenesis. Inflammatory pathways particularly, cyclooxygenase (COX-2) and lipoxygenase (5-LOX) mediated metabolites are known to play important role in bladder tumor progression. Consistent with that epidemiological and clinical observations suggest that use of anti-inflammatory agents is associated with reduced risk for bladder cancer. Here we determined the chemopreventive efficacy of a Licofelone, a dual COX-LOX inhibitor, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC). Six-week old transgenic UPII-SV40T mice (n=30/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm licofelone for 34 weeks. At 40 weeks of age, all mice were euthanized; urinary bladders were collected to determine urothelial tumor weights and histopathological grading. Results suggest that bladders of the control diet fed transgenic mice weighed 3-5 fold more than that of the wild type mice. However, treatment of transgenic mice with licofelone led to a significant, dose dependent inhibition of the urothelial tumor weights (65.2 - 82.7%, p&amp;lt;0.0001 in males; 35.0 - 49.0%, p&amp;lt;0.0001 in females) compared to the control group. Importantly, mice fed licofelone diet significantly reduced development of invasive tumors. Urothelial tumor progression to invasive TCC was inhibited in both male (up to 50%; p&amp;lt;0.01) and females mice (up to 46%; p&amp;lt;0.003). Molecular analysis of urothelial tumors by immuno-histochemisty, qPCR and/or western immunoblotting for the expression of various markers that effect tumor growth and progression showed an increase in apoptosis (p53, p21, Bax, Caspase3, Annexin V) with a decrease in proliferation and angiogenesis (PCNA, COX2, 5LOX, mPGES2, VEGF) in the licofelone diet fed mice tumors. These results suggest that licofelone can serve as potential chemopreventive for bladder TCC. (Supported in part by NCI-CN53300) Citation Format: Venkateshwar Madka, Altaf Mohammed, Qian Li, Yuting Zhang, Laura Biddick, Stanley Lightfoot, Xue-Re Wu, Levy Kopelovich, Vernon Steele, Chinthallapally V. Rao. Licofelone, a dual COX-LOX inhibitor prevents transitional cell carcinoma of urinary bladder in UPII-SV40T transgenic mice. [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 1244. doi:10.1158/1538-7445.AM2014-1244

Overrepresentation of HLA-DQ2 in small intestinal neuroendocrine tumor patients.

Toinvestigate whether celiac disease risk haplotypes HLA-DQ2 and DQ8 also increase the risk for developing small intestinal neuroendocrine tumor (SI-NET). Thirty-five patients with serotonin-producing jejunal and ileal SI-NET were examined with HLA-DQ genotyping and serology for IgA anti-tissue transglutaminase (tTG) antibodies. Twenty-one patients (60 %) carried HLA-DQ2 or DQ8, twice the frequency of the general population (P < 0.001). In particular DQ2 was overrepresented (P = 0.013). Gender, age, disease stage, histopathological grade, or multifocality of primary tumor did not differ between patients with DQ2 or DQ8 and patients with other HLA-DQ haplotypes. No patient in the study was diagnosed with celiac disease (latent or symptomatic) as anti-tTG antibodies were negative in all 35. HLA-DQ haplotypes associated with celiac disease are overrepresented also in patients with SI-NET, in particular HLA-DQ2.