scholarly journals Fascin-1 Is a Novel Prognostic Biomarker Associated With Tumor Invasiveness in Adrenocortical Carcinoma

2018 ◽  
Vol 104 (5) ◽  
pp. 1712-1724 ◽  
Author(s):  
Giada Poli ◽  
Carmen Ruggiero ◽  
Giulia Cantini ◽  
Letizia Canu ◽  
Gianna Baroni ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Tumor Stage ◽  
Labeling Index ◽  
University Hospital ◽  
Adrenal Tumors ◽  
Adrenocortical Cancer ◽  
Tumor Spread ◽  
Adrenocortical Tumors ◽  
Tumor Invasiveness ◽  
Ki67 Labeling Index

Abstract Context Novel tumor markers are urgently needed to better stratify adrenocortical cancer (ACC) patients and improve therapies for this aggressive neoplasm. Objective To assess the diagnostic and prognostic value of the actin-bundling protein fascin-1 (FSCN1) in adrenocortical tumors. Design, Setting and Participants A local series of 37 malignant/37 benign adrenocortical tumors at Careggi University Hospital and two independent validation ACC cohorts (Cochin, TCGA) from the European Network for the Study of Adrenal Tumors were studied. Main Outcome Measures FSCN1 expression was quantified by immunohistochemistry, Western blot and quantitative RT-PCR in ACC specimens; overall and disease-free survival associated with FSCN1 expression were assessed by Kaplan-Meier analysis and compared with that of Ki67 labeling index and tumor stage. Results Despite the low diagnostic power, in the Florence ACC series, FSCN1 immunohistochemical detection appeared as an independent prognostic factor, also refining results obtained with staging and Ki67 labeling index. The robust prognostic power of FSCN1 levels was further confirmed in two independent ACC cohorts. A positive correlation was found between FSCN1 and steroidogenic factor-1 (SF-1), with a substantially higher expression of both factors in ACCs at advanced stages and with at least one of the three Weiss score parameters associated with invasiveness. Moreover, we demonstrated FSCN1 role in promoting cell invasion in a human ACC cell line only in the case of increased SF-1 dosage. Conclusions These findings show that FSCN1 is a novel independent prognostic marker in ACC and may serve as a potential therapeutic target to block tumor spread.

scholarly journals Role of FGF Receptors and Their Pathways in Adrenocortical Tumors and Possible Therapeutic Implications

2021 ◽  
Vol 12 ◽  
Author(s):  
Iuliu Sbiera ◽  
Stefan Kircher ◽  
Barbara Altieri ◽  
Kerstin Lenz ◽  
Constanze Hantel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Kinase Inhibitors ◽  
Univariate Analysis ◽  
Tumor Stage ◽  
Adrenal Tumors ◽  
Ki 67 ◽  
Fgf Receptor ◽  
Therapeutic Implications ◽  
Adrenocortical Tumors

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy and treatment of advanced disease is challenging. Clinical trials with multi-tyrosine kinase inhibitors in the past have yielded disappointing results. Here, we investigated fibroblast growth factor (FGF) receptors and their pathways in adrenocortical tumors as potential treatment targets. We performed real-time RT-PCR of 93 FGF pathway related genes in a cohort of 39 fresh frozen benign and malignant adrenocortical, 9 non-adrenal tissues and 4 cell lines. The expression of FGF receptors was validated in 166 formalin-fixed paraffin embedded (FFPE) tissues using RNA in situ hybridization (RNAscope) and correlated with clinical data. In malignant compared to benign adrenal tumors, we found significant differences in the expression of 16/94 FGF receptor pathway related genes. Genes involved in tissue differentiation and metastatic spread through epithelial to mesechymal transition were most strongly altered. The therapeutically targetable FGF receptors 1 and 4 were upregulated 4.6- and 6-fold, respectively, in malignant compared to benign adrenocortical tumors, which was confirmed by RNAscope in FFPE samples. High expression of FGFR1 and 4 was significantly associated with worse patient prognosis in univariate analysis. After multivariate adjustment for the known prognostic factors Ki-67 and ENSAT tumor stage, FGFR1 remained significantly associated with recurrence-free survival (HR=6.10, 95%CI: 1.78 – 20.86, p=0.004) and FGFR4 with overall survival (HR=3.23, 95%CI: 1.52 – 6.88, p=0.002). Collectively, our study supports a role of FGF pathways in malignant adrenocortical tumors. Quantification of FGF receptors may enable a stratification of ACC for the use of FGFR inhibitors in future clinical trials.

scholarly journals The BRAFV600E Mutation Is Not a Risk Factor for More Aggressive Tumor Behavior in Radiogenic and Sporadic Papillary Thyroid Carcinoma at a Young Age

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6038
Author(s):  
Liudmyla Zurnadzhy ◽  
Tetiana Bogdanova ◽  
Tatiana I. Rogounovitch ◽  
Masahiro Ito ◽  
Mykola Tronko ◽  
...  
Keyword(s):  
Young Patients ◽  
Growth Patterns ◽  
Labeling Index ◽  
Papillary Thyroid ◽  
Chernobyl Fallout ◽  
Virtual Absence ◽  
Tumor Invasiveness ◽  
Ki67 Labeling Index ◽  
Papillary Growth Pattern ◽  
Papillary Growth

Histopathological changes in the fusion oncogene-driven papillary thyroid carcinomas (PTCs) from children and adolescents exposed to Chernobyl fallout have been extensively studied. However, characteristics of the radiogenic BRAFV600E-positive PTCs, whose proportion is growing with time, are not well described yet. We analyzed the relationship between the BRAFV600E status (determined immunohistochemically with the VE1 antibody) and the clinicopathological features of 247 radiogenic and 138 sporadic PTCs from young Ukrainian patients aged ≤28 years. The frequency of BRAFV600E was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAFV600E-positive PTCs more frequently had a dominant papillary growth pattern, smaller tumor size, higher Ki67 labeling index, and a frequency of the major indicators of tumor invasiveness that is lower than or equal to that of the BRAFV600E-negative tumors. Comparison of the BRAFV600E-positive PTCs across the groups found a virtual absence of differences. In contrast, the BRAFV600E-negative radiogenic PTCs displayed less frequent dominant papillary and more frequent solid growth patterns, lower Ki67 labeling index, and higher invasiveness than the BRAFV600E-negative sporadic tumors. Thus, BRAFV600E is not associated with a more aggressive course of PTC in young patients regardless of etiology. The major clinicopathological differences between the radiogenic and sporadic PTCs are observed among the BRAFV600E-negative tumors.

scholarly journals Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Complex ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Prognostic Biomarkers ◽  
High Expression

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

scholarly journals Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zehua Zhang ◽  
Fei Dai ◽  
Fei Luo ◽  
Wenjie Wu ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Proliferation And Metastasis ◽  
New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

scholarly journals Systematic evaluation of scoring methods for Ki67 as a surrogate for 21-gene recurrence score

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Soonmyung Paik ◽  
Youngmee Kwon ◽  
Moo Hyun Lee ◽  
Ji Ye Kim ◽  
Da Kyung Lee ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Recurrence Score ◽  
Predictive Marker ◽  
Labeling Index ◽  
Systematic Evaluation ◽  
Scoring Methods ◽  
Scoring Method ◽  
Ki67 Labeling Index ◽  
Risk Patients ◽  
Potential Clinical Utility

AbstractAlthough Ki67 labeling index is a potential predictive marker for chemotherapy benefit, its clinical utility has been limited by the lack of a standard scoring method resulting in poor interobserver reproducibility. Especially, there is no consensus on the use of average versus hotspot score for reporting. In order to determine the best method for Ki67 scoring and validate manual scoring method proposed by the International Ki67 Working Group (IKWG), we systematically compared average versus hotspot score in 240 cases with a public domain image analysis program QuPath. We used OncotypeDx Recurrence Score (RS) as a benchmark to compare the potential clinical utility of each scoring methods. Both average and hotspot scores showed statistically significant but only modest correlation with OncotypeDx RS. Only hotspot score could meaningfully distinguish RS low-risk versus high-risk patients. However, hotspot score was less reproducible limiting its clinical utility. In summary, our data demonstrate that utility of the Ki67 labeling index is influenced by the choice of scoring method.

scholarly journals Differentiating Benign from Malignant Adrenocortical Tumors by a Single Morphological Parameter—a Clinicopathological Study on 837 Adrenocortical Neoplasias

2020 ◽  
Vol 11 (4) ◽  
pp. 705-710
Author(s):  
Martin K. Walz ◽  
Klaus A. Metz ◽  
Sarah Theurer ◽  
Cathrin Myland ◽  
Pier F. Alesina ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Tumor Necrosis ◽  
Morphological Differentiation ◽  
Scoring Systems ◽  
Distant Metastases ◽  
Adrenal Tumors ◽  
Control Group ◽  
Consecutive Series ◽  
Morphological Parameter ◽  
Adrenocortical Tumors

AbstractThe morphological differentiation between benign and malignant adrenocortical tumors is an ongoing problem in diagnostic pathology. In recent decades the complex scoring systems have been widely used to calculate the probability of malignancy in adrenocortical tumors on the basis of a variety of histomorphological parameters. We herewith present a substantially simplified method to diagnose adrenocortical carcinoma by a single histomorphological parameter on a consecutive series of more than 800 adrenocortical tumors. Between January 2000 and May 2019, altogether 2305 adrenalectomies for of all types of diseases were removed, approximately 98% by minimally invasive approaches. After exclusion of pheochromocytomas, adrenal ganglioneuromas, adrenal metastases, Cushing’s disease related specimens, and Conn’s adenomas, the present series finally consisted of 837 adrenocortical tumors. All tumors were analyzed by experienced pathologists of a single institution using standard histopathological methods (Hematoxylin-Eosin and Ki67 stained sections). Clinical and histopathologic data were prospectively collected and retrospectively analyzed. Clinically, 385 patients had 420 functioning tumors (FT), and 417 had non-functioning adrenal tumors (NFT). The mean size of FT was 3.8 ± 1.4 cm (range 0.5–16 cm) and for NFT 4.5 ± 1.6 cm (range 1.5–18 cm). Histomorphologically, 32 adrenal tumors were classified as adrenocortical carcinoma (ACC; 3.8%). In all 32 cases (tumor size 9.1 ± 4.0 cm, range 3–18 cm), confluenting tumor necrosis could be demonstrated. The remaining 805 tumors (control group) completely lacked this highly reproducible single morphological feature. Ki67 levels above 10% were found in 31 of 32 ACCs and never in adrenocortical adenomas (ACA). With a mean follow-up of 8.2 years, 24 out of 32 patients primarily diagnosed as ACC developed distant metastases (75.0%), whereas all patients in the control group remained free of local or distant recurrence. We conclude that a single morphological parameter (confluenting tumor necrosis) is sufficient to predict a poor clinical course in adrenocortical tumors. The histomorphological diagnosis of this parameter is straightforward and highly reproducible.

A Comparative Study of Epidemiology, Clinicopathologic Features and Outcome of Colorectal Cancer Patients between Ain Shams University Hospitals and Luxor International Hospital

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tarek Hussein Kamel ◽  
Amr Lotfy Farag ◽  
Dr/Sherif Hassanin Ahmed ◽  
Chresteen Talaat Samy Hanna
Keyword(s):  
Colorectal Cancer ◽  
Comparative Study ◽  
Disease Free Survival ◽  
University Hospital ◽  
Treatment Modalities ◽  
Clinicopathologic Features ◽  
Free Survival ◽  
Significant Difference ◽  
Group A ◽  
Group B

Abstract Background Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is the third most common malignancy after lung & breast and the fourth leading cause of cancer-related deaths worldwide, accounting for approximately 1,400,000 new cases and about 700,000 deaths worldwide. Objectives The aim of this retrospective study is to compare the epidemiology, clinicopathologic features, different treatment modalities and outcomes regarding disease free survival (DFS), progression free survival (PFS) & overall survival (OS) of colorectal cancer disease between cases presented to Ain shams university hospital & to Luxor international hospital in 3 consecutive years. Patients and Methods The study is retrospective comparative study. Clinical oncology department in Ain Shams University Hospital and Luxor International Hospital. The data Collected from January 2013 to December 2015. This study analyzed hospital records of patients who diagnosed with colorectal cancer (CRC) and allocated into two groups: Group A: CRC patients presented to Ain-Shams University Hospital from January 2013 to December 2015, group B: CRC patients presented to Luxor International Hospital from January 2013 to December 2015. Results There was no statistically significant difference regarding age parameter in LIH when compared to ASU, but the study was consistent with higher incidence in patients who were aged more than forty- accounted about 70.5% in all CRC cases. Cases less than 40 years old, in group A were 35.2%, while in Group B were 23.5%. Even there was no statistically significant difference but it may be attributable to more westernization in Lower Egypt. Other explanation may be due to decreased low socioeconomic status and different lifestyle factors in more developing region what increase risk of colorectal cancer. Among our cases, there is no statistically significant difference regarding gender between the two hospitals. Both sexes almost were affected equally, females appeared to be at a slightly higher risk of developing CRC cancer with current prevalence 1.3:1 in ASU group, and 1.1:1 in LIH group. Conclusion The need to increase awareness about CRC in Egypt especially upper Egypt, is recommended. An awareness campaign should be performed to promote detection of CRC at its earliest and most curable stage by recognizing early symptoms and enabling early referrals for colonoscopy. Those at higher risk should be offered more intensive surveillance. Similarity of the data from different centers suggests that this is the picture of colorectal cancer typical of Egypt.

scholarly journals Interobserver concordance of Ki67 labeling index in breast cancer: Japan Breast Cancer Research Group Ki67 Ring Study

2013 ◽  
Vol 104 (11) ◽  
pp. 1539-1543 ◽  
Author(s):  
Yoshiki Mikami ◽  
Takayuki Ueno ◽  
Kenichi Yoshimura ◽  
Hitoshi Tsuda ◽  
Masafumi Kurosumi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Research ◽  
Research Group ◽  
Breast Cancer Research ◽  
Labeling Index ◽  
Ki67 Labeling Index

scholarly journals Patients with pheochromocytoma exhibit low aldosterone renin ratio

2020 ◽  
Author(s):  
Tomoko Yamada ◽  
Hidenori Fukuoka ◽  
Yusei Hosokawa ◽  
Yukiko Odake ◽  
Kenichi Yoshida ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Adrenal Adenoma ◽  
Characteristic Curve ◽  
Plasma Renin ◽  
Cross Sectional Study ◽  
University Hospital ◽  
Adrenal Tumors ◽  
Cross Sectional ◽  
Plasma Aldosterone Concentration ◽  
Sensitive Marker

Abstract Background Plasma renin activity (PRA) is generally increased in patients with pheochromocytoma (PCC) due to low circulating plasma volume and activation of β-1 adrenergic receptor signaling. However, there has been no study on the aldosterone renin ratio (ARR) in patients with PCC. To elucidate the issue, this study aimed to determine the PRA, plasma aldosterone concentration (PAC), and ARR in patients with PCC and compare them with those in patients with subclinical Cushing’s syndrome (SCS) and non-functioning adrenal adenoma (NFA). Methods In this retrospective single-center, cross-sectional study, 67 consecutive patients with adrenal tumors (PCC (n =18), SCS (n =18), and NFA (n =31)) diagnosed at Kobe University Hospital between 2008 and 2014 were enrolled. Results PRA was significantly higher in patients with PCC than in those with SCS and NFA (2.1 (1.3~2.8) vs. 0.7 (0.5~1.8) and 0.9 (0.6~1.4) ng/mL/h; p =0.018 and p =0.025). Although PACs were comparable among the three groups, ARR was significantly lower in patients with PCC than in those with SCS and NFA (70.5 (45.5~79.5) vs. 156.0 (92.9~194.5) and 114.9 (90.1~153.4); p =0.001 and p <0.001). Receiver operating characteristic curve analysis demonstrated that, in differentiating PCC from NFA, PRA >1.55 ng/mL/h showed a sensitivity of 70.0% and specificity of 80.6%. Interestingly, ARR <95.4 showed a sensitivity of 83.3% and specificity of 86.7%, which were higher than those in PRA. Conclusions ARR decreased in patients with PCC, which was a more sensitive marker than PRA. Further study is necessary to understand the usefulness of this convenient marker in the detection of PCC.

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