scholarly journals Immunohistochemical Expression of ABCB5 as a Potential Prognostic Factor in Uveal Melanoma

2019 ◽  
Vol 9 (7) ◽  
pp. 1316 ◽  
Author(s):  
Giuseppe Broggi ◽  
Giuseppe Musumeci ◽  
Lidia Puzzo ◽  
Andrea Russo ◽  
Michele Reibaldi ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Target Population ◽  
Metastatic Progression ◽  
Immunohistochemical Expression ◽  
Poor Prognostic Factor ◽  
Expression Levels ◽  
Uveal Tract ◽  
Potential Prognostic Factor

Uveal melanoma represents the most common primary intraocular malignancy in adults; it may arise in any part of the uveal tract, with choroid and ciliary bodies being the most frequent sites of disease. In the present paper we studied ABCB5 expression levels in patients affected by uveal melanoma, both with and without metastasis, in order to evaluate if ABCB5 is associated with a higher risk of metastatic disease and can be used as a poor prognostic factor in uveal melanoma. The target population consisted of 23 patients affected by uveal melanoma with metastasis and 32 without metastatic disease. A high expression of ABCB5 was seen in patients with metastasis (14/23, 60.9%), compared to that observed in patients without metastasis (13/32, 40.6%). In conclusion, we found that ABCB5 expression levels were correlated with faster metastatic progression and poorer prognosis, indicating their role as a prognostic factor in uveal melanoma.

scholarly journals Immunoexpression of Macroh2a in Uveal Melanoma

2019 ◽  
Vol 9 (16) ◽  
pp. 3244 ◽  
Author(s):  
Salvatorelli ◽  
Puzzo ◽  
Bartoloni ◽  
Palmucci ◽  
Longo ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Cutaneous Melanoma ◽  
High Expression ◽  
Melanoma Metastasis ◽  
Proper Treatment ◽  
Immunohistochemical Expression ◽  
Prognostic Role

MacroH2A is a histone variant whose expression has been studied in several neoplasms, including cutaneous melanomas (CMs). In the literature, it has been demonstrated that macroH2A.1 levels gradually decrease during CM progression, and a high expression of macroH2A.1 in CM cells relates to a better prognosis. Although both uveal and cutaneous melanomas arise from melanocytes, uveal melanoma (UM) is biologically and genetically distinct from the more common cutaneous melanoma. Metastasis to the liver is a frequent occurrence in UM, and about 40%–50% of patients die of metastatic disease, even with early diagnosis, proper treatment, and close follow-up. We wanted to investigate macroH2A.1 immunohistochemical expression in UM. Our results demonstrated that mH2A.1 expression was higher in metastatic UM (21/23, 91.4%), while only 18/32 (56.3%). UMs without metastases showed mH2A.1 staining. These data could suggest a possible prognostic role for mH2A.1 and could form a basis for developing new pharmacological strategies for UM treatment.

Immunohistochemical expression of core 2 β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1) in endometrioid-type endometrial carcinoma: a novel potential prognostic factor

2013 ◽  
Vol 62 (7) ◽  
pp. 986-993 ◽  
Author(s):  
Tsutomu Miyamoto ◽  
Akihisa Suzuki ◽  
Ryoichi Asaka ◽  
Kaori Ishikawa ◽  
Yasushi Yamada ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Endometrial Carcinoma ◽  
Immunohistochemical Expression ◽  
Potential Prognostic Factor

scholarly journals Targeting Oncogenic Gαq/11 in Uveal Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6195
Author(s):  
Dominic Lapadula ◽  
Jeffrey L. Benovic
Keyword(s):  
Transcription Factor ◽  
Signaling Pathways ◽  
G Proteins ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Therapeutic Strategy ◽  
Activating Mutations ◽  
Alpha Subunits ◽  
Uveal Tract ◽  
Selective Targeting

Uveal melanoma is the most common intraocular cancer in adults and arises from the transformation of melanocytes in the uveal tract. While treatment of the primary tumor is often effective, 36–50% of patients develop metastatic disease primarily to the liver. While various strategies have been used to treat the metastatic disease, there remain no effective treatments that improve survival. Significant insight has been gained into the pathways that are altered in uveal melanoma, with mutually exclusive activating mutations in the GNAQ and GNA11 genes being found in over 90% of patients. These genes encode the alpha subunits of the hetetrotrimeric G proteins, Gq and G11, and mutations result in activation of several important signaling pathways, including phospholipase C and activation of the transcription factor YAP. In this review, we discuss current efforts to target various signaling pathways in the treatment of uveal melanoma including recent efforts to target Gq and G11 in mouse models. While selective targeting of Gq and G11 provides a potential therapeutic strategy to treat uveal melanoma, it is evident that improved inhibitors and methods of delivery are needed.

Characterizing the landscape of genomic variants in high-risk pediatric osteosarcoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11530-11530
Author(s):  
Amanda Marinoff ◽  
Liam F. Spurr ◽  
Duong Doan ◽  
Laura Corson ◽  
Abigail Ward ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Factor ◽  
Metastatic Disease ◽  
Statistical Significance ◽  
Large Population ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Entire Study ◽  
Poor Prognostic Factor ◽  
Profile Study

11530 Background: Survival rates for patients with metastatic and/or recurrent osteosarcoma are poor, and treatment strategies have remained unchanged for more than three decades. Genomic characterization can identify new treatment strategies and improve risk stratification. To date, sequencing studies of osteosarcoma have focused on newly diagnosed patients. We present one of the first reports of osteosarcoma genomics in a high-risk cohort. Methods: 92 samples from 92 patients were sequenced in a CLIA/CAP laboratory with a targeted NGS panel test. Patients were enrolled in one of two studies. The PROFILE study enrolls all patients seen at Dana-Farber Cancer Institute, and the GAIN study enrolls patients with metastatic and/or recurrent cancer at 11 institutions. Sequencing was performed using primary tumor samples at biopsy and/or from sites of metastasis when available. Results: 33 patients were enrolled on the PROFILE study, and 59 were enrolled on GAIN. Diagnostic stage was available for 65 (67%) of patients. 37% had metastatic disease at diagnosis. The 3-year overall survival (OS) was 71% for the entire study population, 56% for patients with metastatic disease at diagnosis, and 81% for patients with initially localized disease. The presence of metastases at diagnosis was significantly associated with poor outcome (p < 0.0087) and was the only independent clinical prognostic factor identified. Genomic analysis revealed frequent alterations in TP53 (37%), RB1 (15%), CDKN2A (13%), MYC (12%), CDKN1A (12%), ATRX (10%), and CCND3 (8%). Patients whose tumors had MYC amplification (defined as ≥ 6 copies) had a 3-year OS of 39% compared with a 3-year OS of 76% in the absence of MYC amplification, a difference with borderline statistical significance (p = 0.051). Conclusions: In the first study to examine genomic alterations detected by targeted gene panel sequencing in a CAP-certified laboratory in a large population of pediatric patients with higher risk osteosarcoma, the most frequently occurring events were similar to those found in prior reports. MYC amplification, reported as a possible poor prognostic factor in other studies, was present in 12% of patients and was associated with a worse OS, though this finding did not reach statistical significance.

scholarly journals Fatty acid synthase, a novel poor prognostic factor for acute lymphoblastic leukemia which can be targeted by ginger extract

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maryam Ghaeidamini Harouni ◽  
Soheila Rahgozar ◽  
Somayeh Rahimi Babasheikhali ◽  
Arman Safavi ◽  
Elaheh Sadat Ghodousi
Keyword(s):  
Fatty Acid ◽  
Acute Lymphoblastic Leukemia ◽  
Prognostic Factor ◽  
Fatty Acid Synthase ◽  
Lymphoblastic Leukemia ◽  
Combined Treatment ◽  
Drug Resistant ◽  
Poor Prognostic Factor ◽  
Expression Levels ◽  
The Impact

AbstractAltered metabolism of fatty acid synthesis is considered a hallmark characteristic of several malignancies, including acute lymphoblastic leukemia (ALL). To evaluate the impact of fatty acid synthase (FASN) on drug resistant ALL, bone marrow samples were collected from 65 pediatric ALLs, including 40 de novo and 25 relapsed patients. 22 non-cancer individuals were chosen as controls. Quantitative RT-PCR showed increased expression levels of FASN in drug resistant patients compared with the therapy responders. Single and combined treatment of malignant cells were analyzed using Annexin-V/PI double staining and MTT assays. Incubation of resistant primary cells with ginger showed simultaneous increased apoptosis rates and reduced FASN expression levels. Furthermore, docking studies demonstrated high affinity bindings between ginger derivatives and FASN thioesterase and ketosynthase domains, compared with their known inhibitors, fenofibrate and morin, respectively. Finally, combined treatment of in-house multidrug resistant T-ALL subline with ginger and dexamethasone induced drug sensitivity and down regulation of FASN expression, accordingly. To the best of our knowledge, this is the first study that introduces FASN upregulation as a poor prognostic factor for drug resistant childhood ALL. Moreover, it was revealed that FASN inhibition may be applied by ginger phytochemicals and overcome dexamethasone resistance, subsequently.

PRDX3 is associated with metastasis and poor survival in uveal melanoma

2019 ◽  
Vol 73 (7) ◽  
pp. 408-412 ◽  
Author(s):  
Pathma Ramasamy ◽  
Anne-Marie Larkin ◽  
Annett Linge ◽  
Damien Tiernan ◽  
Fionnuala McAree ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Immunohistochemical Staining ◽  
Significant Negative Correlation ◽  
Immunohistochemical Expression ◽  
Poor Survival ◽  
Kaplan Meier ◽  
Formalin Fixed Paraffin ◽  
Significant Difference ◽  
Formalin Fixed Paraffin Embedded

AimsUveal melanoma (UM) is the most common primary intraocular malignancy in adults, and 40% develop fatal metastatic disease. Overexpression of thioredoxin-dependent peroxidase reductase (PRDX3) has been implicated in several cancers, including prostate, breast, colorectal and lung cancer. The aim of this study was to compare the immunohistochemical expression of PRDX3 in formalin-fixed, paraffin-embedded (FFPE) primary UM tissues of patients who did and did not develop metastatic disease.MethodsImmunohistochemical staining of PRDX3 was performed on FFPE tissue microarray samples of 92 primary UM tumours from patients who did and did not develop metastatic disease. The immunohistochemical staining was assessed by two observers who were blinded to all clinicopathological and cytogenetic details including metastatic/non-metastatic information. Based on a scoring system, expression of PRDX3 was graded as high or low.ResultsThere were 55 tumours (59.8%) from patients who developed metastatic disease, while 37 (40.2%) were from patients who did not develop metastasis. A statistically significant difference in PRDX3 expression was observed in patients who did and did not develop metastasis (p=0.001). A significant positive correlation between high PRDX3 expression and metastasis was observed (p=0.001). A significant negative correlation between PRDX3 expression and survival was found (p=0.005). Kaplan-Meier survival analysis showed a statistically significant difference in overall survival between tumours that demonstrated low and high expression of PRDX3 (67.61 vs 130.64 months, respectively, p=0.013).ConclusionsHigh immunohistochemical expression of PRDX3 in primary UM tissue is associated with metastasis and poor survival.

scholarly journals Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1796
Author(s):  
Markus Eckstein ◽  
Verena Lieb ◽  
Rudolf Jung ◽  
Danijel Sikic ◽  
Katrin Weigelt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Immune Cells ◽  
Potential Candidate ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Muscle Invasive ◽  
Disease Specific

Urothelial bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide and accounts for approximately 3% of global cancer diagnoses. We are interested in prognostic markers that may characterize tumor cells (TCs) and immune cells (ICs) and their relationship in BCa. A potential candidate marker that meets these criteria is progranulin (GP88), which is expressed separately in TCs and ICs. We analyzed GP88 expression by immunohistochemistry (IHC) in 196 muscle-invasive BCa samples using a tissue microarray. The immunoreactive score for GP88 staining in TCs and the percentage of GP88-positive ICs was determined. An easy cutoff for the staining status of TCs (positive vs. negative) and ICs (0% vs. >0%) and, more generally, negative vs. positive GP88 staining could be applied. We detected 93 patients (47.4%) and 92 patients (46.9%) with GP88-positive TCs or ICs, respectively. The IHC results were correlated with clinicopathological and survival data. Positive GP88 staining in TCs appeared to be an independent poor prognostic factor for disease-specific survival (DSS) (RR (relative risk) = 1.74; p = 0.009) and recurrence-free survival (RFS) (RR = 1.92; p = 0.002). In contrast, negative GP88 staining in ICs was an independent negative predictor for overall survival (OS) (RR = 2.18; p < 0.001), DSS (RR = 2.84; p < 0.001) and RFS (RR = 2.91; p < 0.001) in multivariate Cox’s regression analysis. When combining GP88 staining in TCs and ICs, a specific combination of GP88-positive TCs and GP88-negative ICs was associated with a 2.54-fold increased risk of death, a 4.21-fold increased risk of disease-specific death and a 4.81-fold increased risk of recurrence compared to GP88-negative TCs and GP88-positive ICs. In summary, GP88 positivity in TCs is a negative prognostic factor for DSS and RFS. In addition, GP88 positivity can mark ICs that are associated with a good prognosis (OS, DSS and RFS). The combination of GP88 staining in TCs and ICs appears to be a significant independent prognostic biomarker in muscle-invasive BCa.

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