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.

scholarly journals Expression of the Metastasis Suppressor KAI1 in Uveal Melanoma

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Shawn C. Maloney ◽  
Bruno F. Fernandes ◽  
Rafaella Cleto Penteado ◽  
Emilia Antecka ◽  
Vasco Bravo-Filho ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Staining Intensity ◽  
Suppressor Gene ◽  
Metastasis Suppressor ◽  
Efficacious Treatment ◽  
Therapeutic Value ◽  
Group 2 ◽  
Group 1

Introduction. Uveal melanoma (UM) is an intraocular tumor that leads to metastatic disease in approximately 50% of afflicted patients. There is no efficacious treatment for metastatic disease in this cancer. Identification of markers that can offer prognostic and therapeutic value is a major focus in this field at present. KAI1 is a metastasis suppressor gene that has been reported to play a role in various human malignancies, although it has not previously been evaluated in UM.Purpose. To investigate the expression of KAI1 in UM and its potential value as a prognostic marker.Materials and Methods. 18 cases of human primary UM were collected and immunostained for KAI1 expression. A pathologist evaluated staining intensity and distribution semiquantitatively. Each case was categorized as group 1 (low staining) or group 2 (high staining).Results. In group 2, two of the 12 cases presented with metastasis. Conversely, in group 1, five out of 6 cases had metastasis. The mean follow-up of patients who did not develop metastasis was 81.81 months (median: 75 months) versus 42.14 months (median: 44 months) for patients with metastasis.Conclusions. KAI1 is a promising candidate marker that may offer prognostic value in UM; it may also represent a therapeutic target in metastatic disease.

Molecular profiling and clinical characteristic of malignant melanoma in younger patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22087-e22087
Author(s):  
Jomjit Chantharasamee ◽  
Karlton Wong ◽  
Bartosz Chmielowski
Keyword(s):  
Gene Expression ◽  
General Population ◽  
Uveal Melanoma ◽  
Cutaneous Melanoma ◽  
Stage I ◽  
Stage Iii ◽  
Younger Patients ◽  
Adjuvant Immunotherapy ◽  
Better Than

e22087 Background: Combination of clinical and molecular data has not yet been well established in adolescent and younger adult patients with melanoma Methods: We performed a retrospective analysis of the molecular profiles and clinical outcome of patients diagnosed at the age younger than 40 treated at UCLA during 2010 to 2019. Patient’s molecular profile, characteristics, and treatment outcome were described using descriptive statistic. Kaplan-Meier curve was used for disease-free survival (DFS) and overall survival (OS). Results: 150 patients with a median age of 29 year (12-39) were analyzed. 101 (67.3%) patients had cutaneous melanoma, 49 (32.7%) had localized uveal melanoma. Of those 101, 23.8% had pre-existing benign or congenital nevus. 70/101 (69.3%) was stage I-II, 26/101 (25.7%) stage III and 5/101 (4.9%) stage IV. Of those 37 patients with molecularly characterized tissue, 23 (62%) had BRAF mutation including 17 V600E, 4 V600 unknown codon, 2 G469A, 2 NRAS and 1 NF-1 mutation. 11/37 were BRAF negative. 79.6% of patients who were not tested were stage I. For patients with stage III, 16/26 (61%) received adjuvant immunotherapy, none of adjuvant targeted therapy. At 35.1 months follow-up time, 27/96 (28%) localized cutaneous melanoma experienced relapse. 1-year DFS was 73% in adjuvant vs. 90% in no adjuvant immunotherapy group. Among 49 uveal melanoma patients, the median age was 27 years old. 23/49 (49%) had a T1 tumor, 18/49 (36.7%) T2, 6/49(12.2%) T3, 1/49(2%) T4. At 45 months follow-up time, three (6.1%) patients developed metastasis. 5-year DFS and OS was 90% and 100%, respectively. 45 patients had tissue for gene expression profiling and/or FISH testing. 15/45 (33%) had class IA, 13/45 (28%) had class IB, and 8/45 (17.7%) had class 2. 24 samples were analyzed by FISH: 14 with disomy 3, 5 with complex disomy 3 with gain of chromosome 6 or 8, and 5 with monosomy 3. Conclusions: Similarly to general population, most of younger patients with melanoma are diagnosed with stage I disease. Among patients with stage III melanoma treated with adjuvant immunotherapy 1-year DFS was comparable to the general population. Patients with stage III who did not receive adjuvant therapy had an excellent DFS which confirms that the decision on selecting patients for treatment was appropriate. The prognosis of younger patients with uveal melanoma was much better than predicted by molecular testing, and much better than expected regardless of gene expression profile or cytogenetic testing.

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 Prognostic Value of Autophagy-related Genes Correlated With Metastasis in Uveal Melanoma Patients

2021 ◽  
Author(s):  
Yan Sun ◽  
Xiaoran Wang ◽  
Baoxin Chen ◽  
Lang Xiong ◽  
Jingqi Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Survival Analysis ◽  
Uveal Melanoma ◽  
Risk Score ◽  
Protein Interactions ◽  
Cox Regression ◽  
Early Stage ◽  
Expression Profiles ◽  
High Expression ◽  
Melanoma Metastasis

Abstract Half of the patients with primary uveal melanoma will develop progressive metastasis, leading to high mortality rate. Autophagy has been demonstrated to engage in metastasis in multiple tumors. Detection, diagnosis and treatment at the early-stage of uveal melanoma may help prevent potential tumor progression and optimize the prognosis. The purpose of our study was to discover autophagy-related genes (ARGs) correlated with uveal melanoma metastasis and determine their prognostic values. We analyzed the gene expression profiles and the clinical data from the Gene Expression Omnibus (GEO) database in uveal melanoma. A total of 14 and 16 differentially expressed ARGs were identified to be related to uveal melanoma metastasis from GSE22138 and GSE27831 sets. The two datasets shared three common genes including RAF1, CDKN1A and WIPI1 that occupied the core positions in the Protein-Protein Interactions (PPI) Network of ARGs. Following that, TCGA was introduced for survival analysis of the three genes. The survival analysis showed that high expression of RAF1 was related to favorable prognosis of uveal melanoma, whereas high expression of CDKN1A and WIPI1 suggested poor prognosis. Then a three-ARG based prognostic risk score model was constructed to predict survival outcomes. Univariate and multivariate Cox regression analyses indicated that the risk score can be considered as an independent prognostic factor for uveal melanoma, exhibiting good accuracy and sensitivity. In summary, we established an autophagy-related prognostic model based on uveal melanoma metastasis, which may contribute to the detection of early metastasis and prediction of prognosis, thereby prolonging survival through early personalized intervention.

Immune profile of metastatic uveal melanoma during treatment with pembrolizumab.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9536-9536
Author(s):  
Ernesto Rossi ◽  
Ilaria Zizzari ◽  
Giovanni Schinzari ◽  
Alessandra Di Filippo ◽  
Brigida Anna Maiorano ◽  
...  
Keyword(s):  
T Cells ◽  
Uveal Melanoma ◽  
Cutaneous Melanoma ◽  
Immune Checkpoints ◽  
Soluble Form ◽  
Immunological Parameters ◽  
Blood Samples ◽  
Low Levels ◽  
Potential Factors

9536 Background: Metastatic uveal melanoma (mUM) is a rare and aggressive disease. No standard therapy has been established. All the available treatments derive from trials in cutaneous melanoma. A minority of patients with mUM can benefit from immunotherapy. Immunological features of a group of patients with metastatic UM treated with Pembrolizumab were analyzed in order to explore the immune-response in this disease and the potential factors able to select the patients who can benefit from immunotherapy. Methods: Blood samples from 12 UM patients before (T0) and during treatment with Pembrolizumab (T1: after 1 cycle of Pembrolizumab; T2: after 3 cycle of Pembrolizumab) were collected. Peripheral blood mononucleated cells (PBMCs) were isolated and characterized for markers expression. Sera were analyzed for a panel of soluble (s) immune checkpoints and cytokines. The correlation between immunological parameters with PFS and OS was explored. Blood samples from 6 metastatic cutaneous melanoma (CM) patients with a confirmed response to anti PD-1 agents were also collected during the treatment and analyzed for PBMCs and sera. Results: Soluble CTLA4, sPD-L1, sCD137, sTIM3 were significantly higher in UM than in CM. CD137 was significantly higher in UM patients progressed with Pembrolizumab than in the 2 responsive patients (512 pg/ml vs < 12.9 pg/ml, respectively, p = 0.04) who are still alive and on treatment after a median follow-up of 24 months. Low sGITR, sCD137, sHVEM, and sTIM3 are associated with longer PFS. IL-8 was lower in CM than UM (2.5 pg/ml vs 40.7 pg/ml) and in the responsive versus progressed UM patients (3,7 pg/ml vs 118 pg/ml, p = 0,042). Low levels of IL-8 and IL-1-alpha are significantly associated with longer PFS (p = 0.011 and 0.010 respectively). In responsive patients CD137 expression on CD3+, CD4+ and CD8+ T cells was higher than in progressed patients, while sCD137 was absent. Conclusions: A group of s-immune checkpoints and cytokines correlate with Pembrolizumab effectiveness in mUM. High expression of CD137 on T cells associated with the absence of its soluble form in responders could suggest the correlation between the retention of this co-stimulatory molecule and efficacy of anti-PD1.

scholarly journals Stability of early treatment of anterior open bite: clinical performance of bonded lingual spurs

2019 ◽  
Vol 46 (1) ◽  
pp. 68-73
Author(s):  
Flaviana Alves Dias ◽  
Flávia Diane Assis Urnau ◽  
Paula Vanessa Pedron Oltramari ◽  
Marcelo Lupion Poleti ◽  
Marcio Rodrigues de Almeida ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Early Treatment ◽  
Clinical Performance ◽  
Open Bite ◽  
Proper Treatment ◽  
Anterior Open Bite ◽  
Psychological Issues ◽  
Advanced Therapy ◽  
One Year

Anterior open bite (AOB) is a malocclusion that generates aesthetic, speech, feeding and psychological issues, a fact that emphasises the importance of conducting early treatments to fix the disorder. Finger-sucking, pacifiers and oral habits are the main aetiological factors of AOB; thus, it is necessary to apply interceptive treatments focused on correcting and improving bite stability during childhood in order prevent the need of undergoing advanced therapy. The aim of this article is to present the early diagnosis of aetiological factors causing severe AOB and the interceptive treatment based on the use of bonded lingual spurs for one year. Results showed excellent bite stability after two years of follow-up; in other words, the proper treatment applied for the recommended growth and developmental periods enabled case stability.

scholarly journals Recurrence of uveal malignant melanoma: a case report

2013 ◽  
Vol 5 (2) ◽  
pp. 275-278
Author(s):  
Madhu Thapa ◽  
GB Shrestha ◽  
AK Sharma ◽  
S Karki ◽  
S Khanal
Keyword(s):  
Case Report ◽  
Adjuvant Chemotherapy ◽  
Malignant Melanoma ◽  
Early Diagnosis ◽  
Uveal Melanoma ◽  
Unusual Case ◽  
Uveal Tract ◽  
Uveal Malignant Melanoma ◽  
Ocular Morbidity

Background: Malignant melanoma of uveal tract is a rare ocular malignancy. It is one of the significant causes of ocular morbidity and mortality which is less commonly seen in children. Case: We report an unusual case of orbital recurrence of malignant melanoma in a 14-yearold boy who had previously undergone enucleation of the left painful blind eye 8 months ago. He was diagnosed to have uveal malignant melanoma elsewhere which was confirmed by histopathology. Orbital recurrence was managed with modified exenteration with adjuvant chemotherapy and radiotherapy. Conclusion: In all treated cases of uveal melanoma, close follow up examination and monitoring is necessary for early diagnosis of the recurrence and to plan for further management. Nepal J Ophthalmol 2013; 5(10): 275-278 DOI: http://dx.doi.org/10.3126/nepjoph.v5i2.8744

Variates of Survival in Metastatic Uveal Melanoma

2005 ◽  
Vol 23 (31) ◽  
pp. 8076-8080 ◽  
Author(s):  
Petra Rietschel ◽  
Katherine S. Panageas ◽  
Christine Hanlon ◽  
Ami Patel ◽  
David H. Abramson ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Initial Diagnosis ◽  
Screening Tests ◽  
Cancer Center ◽  
Common Site ◽  
Asymptomatic Patients ◽  
Diagnosis Date ◽  
Single Organ

Purpose The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival. Patients and Methods All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy. Results The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis. Conclusion A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.

scholarly journals Prognostic Role of Non-Identification of Sentinel Lymph Node in Cutaneous Melanoma Patients: An Observational Retrospective Study

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3151
Author(s):  
Ruggero Moro ◽  
Cintia Arjona-Aguilera ◽  
Celia Requena ◽  
Virginia Pont-Sanjuan ◽  
Victor Traves ◽  
...  
Keyword(s):  
Lymph Node ◽  
Retrospective Study ◽  
Sentinel Lymph Node ◽  
Cutaneous Melanoma ◽  
Disease Free Survival ◽  
Prognostic Role ◽  
Free Survival ◽  
Melanoma Patients

Background: Sentinel lymph node (SLN) status is recognized as the most important prognostic factor for patients with cutaneous melanoma. However, sometimes it is not possible to identify SLN. The phenomenon of non-identification of SLN and its prognostic role have not been thoroughly evaluated in melanoma literature. The objective of this study was to identify which patient or tumor variables may be associated to non-identification of SLN and to evaluate the prognostic role of non-identification of SLN. Methods: Observational retrospective study of 834 cutaneous melanoma patients who underwent SLN biopsy at Instituto Valenciano de Oncología. Results: Forty-two patients (5%) presented non-identification of SLN. Patients with age at diagnosis of ≥ 64 years, obesity (BMI ≥ 30), and head and neck localization were at higher risk of non-identification of SLN. Non-identified SLN patients had worse nodal disease-free survival with respect to negative SLN patients, but not worse melanoma-specific survival. Conclusions: Our findings suggest a need to follow-up patients with non-identified SLN in the same way as patients with positive SLN.

scholarly journals The Macro-Autophagy-Related Protein Beclin-1 Immunohistochemical Expression Correlates With Tumor Cell Type and Clinical Behavior of Uveal Melanoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Giuseppe Broggi ◽  
Antonio Ieni ◽  
Daniela Russo ◽  
Silvia Varricchio ◽  
Lidia Puzzo ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Human Cancer ◽  
Malignant Neoplasm ◽  
Disease Free Survival ◽  
Beclin 1 ◽  
Survival Times ◽  
Immunohistochemical Expression ◽  
Prognostic Role ◽  
Long Time ◽  
Related Proteins

Uveal melanoma, in spite of its rarity, represents the most common primitive intraocular malignant neoplasm of the adults; it affects choroid, ciliary bodied and iris and remains clinically silent for a long time, being accidentally discovered by routine ophthalmic exams. Prognosis of uveal melanoma is poor and frequently characterized by liver metastases, within 10–15 years from diagnosis. Autophagy is a multi-step catabolic process by which cells remove damaged organelles and proteins and recycle nutrients. It has been hypothesized that in early stages of tumorigenesis autophagy has a tumor suppressor role while, in more advanced stages, it may represent a survival mechanism of neoplastic cells in response to stress. Several proteins related to autophagy cascade have been investigated in numerous subtypes of human cancer, with overall controversal results. In this paper we studied the immunohistochemical expression of 3 autophagy related proteins (Beclin-1, p62 and ATG7) in a cohort of 85 primary uveal melanoma treated by primary enucleation (39 with metastasis and 46 non metastatic) and correlated their expression with clinico-pathological parameters and blood vascular microvessel density, in order to investigate the potential prognostic role of autophagy in this rare neoplasm. We found that high immunohistochemical levels of Beclin-1 correlated with a lower risk of metastasis and higher disease-free survival times, indicating a positive prognostic role for Beclin-1 in uveal melanoma. No statistically significative differences regarding the expression of ATG7 and p62 between metastatic and non metastatic patients was detected.

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