Prognostic Factor Utility of BAP1 Immunohistochemistry in Uveal Melanoma: A Single Center Study in Spain

Even today, the mortality rate for uveal melanoma (UM) remains very high. In our research, we sought to determine which pathological and clinical features were correlated with the prognosis of UM. BAP1 (BRCA1-Associated Protein 1) gene mutation has been analyzed as one of the strongest predictors for metastasis in UM. The BAP1 gene codifies the BAP1 protein which has a tumor suppressor function. The presence of this protein can be determined by BAP1 immunohistochemical staining. Eighty-four uveal melanoma patients and forty enucleated eyeballs were examined. Metastasis was present in 24 patients. Nuclear BAP1 staining was low in 23 patients. The presence of a higher large basal diameter tumor (p < 0.001), tumor infiltrating lymphocytes (p = 0.020), and a lack of nuclear BAP1 immunostaining (p = 0.001) ocurred significantly more often in the metastatic group. Metastasis-free survival was lower in patients with low nuclear BAP1 staining (p = 0.003). In conclusion, to the best of our knowledge, this is the first time that BAP1 staining has been studied in uveal melanoma in a Spanish community. We believe that this technique should become routine in the pathological examination of uveal melanoma in order to allow adequate classification of patients and to establish an individual follow-up plan.

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Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14035 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14035-e14035

Author(s):

Daniele Fanale ◽

Lorena Incorvaia ◽

Gaetana Rinaldi ◽

Lidia Terruso ◽

Giuseppe Badalamenti ◽

...

Keyword(s):

Metastatic Melanoma ◽

Primary Tumor ◽

Primary Melanoma ◽

Tumor Infiltrating Lymphocytes ◽

Rank Test ◽

Expression Levels ◽

Kaplan Meier ◽

Melanoma Patients ◽

Infiltrating Lymphocytes ◽

First Time

e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasma PD-1 levels were analyzed in 28 patients with metastatic melanoma using a specific ELISA assay. The characterization of TILs in tumor tissue was performed by immunohistochemistry. Statistical analysis was assessed using t-Student and ANOVA tests. Survival curves were estimated by using the Kaplan-Meier method and log-rank test to evaluate significant differences among them. Results: 16 out of 28 patients showed the presence of TILs in primary tumor, 10 of which brisk and 6 nonbrisk. The plasma PD-1 levels were analyzed in relation to the presence/absence of TILs (p = 0.022), brisk TILs versus nonbrisk/absent TILs (p = 0.014), and brisk vs nonbrisk vs absent TILs (p = 0.032). In particular, low plasma PD-1 levels have been shown to be associated with brisk TILs in primary melanoma, intermediate values with nonbrisk TILs, and high expression with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant association between the plasma PD-1 expression levels and overall survival (OS) depending on the absence or presence of TILs (brisk/nonbrisk), however the median survival of patients having brisk TILs was five months higher than other 2 groups of patients with absent and nonbrisk TILs, respectively. Conclusions: This work highlights, for the first time, the potential ability of using the plasma PD-1 levels to predict prognosis also in patients with metastatic melanoma at diagnosis for which it is not possible to identify the primary tumor.

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Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

Journal of Immunology Research ◽

10.1155/2018/3530148 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Mélanie Saint-Jean ◽

Anne-Chantal Knol ◽

Christelle Volteau ◽

Gaëlle Quéreux ◽

Lucie Peuvrel ◽

...

Keyword(s):

Cell Therapy ◽

Adoptive Cell Therapy ◽

Interleukin 2 ◽

Tumor Infiltrating Lymphocytes ◽

Advanced Melanoma ◽

Autologous Tumor ◽

Unresectable Stage ◽

Melanoma Patients ◽

Infiltrating Lymphocytes

Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4) or IV (n=6) melanoma. All but 1 patient with unresectable stage III melanoma (1st line) had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation.

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Laparoscopic Resection of Renal Capsular Endometriosis in a Woman with Menstrual-Related Flank Pain: Case Report

African Journal of Urology ◽

10.1186/s12301-021-00186-2 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Abbas Basiri ◽

Iman Ghanaat ◽

Hamidreza Akbari Gilani

Keyword(s):

Flank Pain ◽

Pathological Examination ◽

Histologic Evaluation ◽

Normal Renal Parenchyma ◽

Perinephric Space ◽

Superior Portion ◽

The Right ◽

First Time ◽

Laparoscopic Removal

Abstract Background Although involvement of the urinary system is not uncommon, endometriosis in the kidneys is rare. To date, laparoscopic partial nephrectomy has been the preferred approach for managing renal endometriosis. Here, we report for the first time the results of laparoscopic removal of a renal capsular endometriosis in a malrotated kidney in an attempt to save the whole kidney parenchyma, in terms of feasibility and safety. Case presentation A 37-year-old female presented with periodic right flank pain associated with her menstrual cycle. On imaging, a malrotated right kidney and a hypodense irregular-shaped lesion measuring 30 * 20 * 15 mm were seen in the superior portion of the right perinephric space. Histologic evaluation of the ultrasound-guided biopsy was consistent with renal capsular endometriosis. The patient underwent laparoscopic surgery to remove the capsular mass while preserving the normal renal parenchyma. Pathological examination of the biopsy obtained during surgery was in favor of renal endometriosis. At 6-month follow-up, the patient’s pain had completely disappeared and no complications had occurred. In addition, imaging did not show any remarkable recurrence. Conclusion Renal endometriosis should be strongly considered as a differential diagnosis in female patients with a renal capsular mass and exacerbation of flank pain during menstruation. Based on our experience, with preoperative needle biopsy and clearing the pathology, laparoscopic removal of the mass in spite of renal anatomic abnormality is feasible and safe and thus could be considered as a possible treatment option.

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Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919848872 ◽

2019 ◽

Vol 11 ◽

pp. 175883591984887 ◽

Cited By ~ 5

Author(s):

Lorena Incorvaia ◽

Giuseppe Badalamenti ◽

Gaetana Rinaldi ◽

Juan Lucio Iovanna ◽

Daniel Olive ◽

...

Keyword(s):

Immune Response ◽

Overall Survival ◽

Survival Rate ◽

Metastatic Melanoma ◽

Braf Mutation ◽

Primary Melanoma ◽

Tumor Infiltrating Lymphocytes ◽

Enzyme Linked Immunosorbent Assay ◽

Melanoma Patients ◽

Infiltrating Lymphocytes

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients’ overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis.

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Prospective evaluation of risk-appropriate management of uveal melanoma patients informed by gene expression profiling

Melanoma Management ◽

10.2217/mmt-2020-0001 ◽

2020 ◽

Vol 7 (1) ◽

pp. 17-25 ◽

Cited By ~ 1

Author(s):

Amy C Schefler ◽

Alison Skalet ◽

Scott C N Oliver ◽

John Mason ◽

Anthony B Daniels ◽

...

Keyword(s):

Gene Expression ◽

Uveal Melanoma ◽

Clinical Utility ◽

Medical Oncology ◽

Treatment Plan ◽

Risk Class ◽

Class 1 ◽

Melanoma Patients ◽

Metastatic Risk

Aim: The Clinical Application of DecisionDx-UM Gene Expression Assay Results study aimed to evaluate the clinical utility of the prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) patients in a large, prospective multicenter cohort. Patients & methods: Nine centers prospectively enrolled 138 UM patients clinically tested with the 15-GEP. Physician-recommended specialty referrals and metastatic surveillance regimens were collected. Results: A total of 93% of high-risk class 2 patients were referred to medical oncology for follow-up, compared with 51% of class 1 patients. A majority (62%) of class 2 patients were recommended overall high-intensity metastatic surveillance, while 85% of class 1 patients were recommended low-intensity metastatic surveillance. Conclusion: Treatment plan recommendations for UM patients are aligned with GEP-informed metastatic risk, consistent with prior studies.

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An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma

Nature Communications ◽

10.1038/s41467-019-13043-2 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 7

Author(s):

Balazs Acs ◽

Fahad Shabbir Ahmed ◽

Swati Gupta ◽

Pok Fai Wong ◽

Robyn D. Gartrell ◽

...

Keyword(s):

Open Source ◽

Open Source Software ◽

Tumor Infiltrating Lymphocytes ◽

Independent Prognostic Marker ◽

Scoring Algorithm ◽

Multivariable Analyses ◽

Melanoma Patients ◽

Independent Association ◽

Infiltrating Lymphocytes ◽

Hematoxylin Eosin

AbstractAssessment of tumor infiltrating lymphocytes (TILs) as a prognostic variable in melanoma has not seen broad adoption due to lack of standardization. Automation could represent a solution. Here, using open source software, we build an algorithm for image-based automated assessment of TILs on hematoxylin-eosin stained sections in melanoma. Using a retrospective collection of 641 melanoma patients comprising four independent cohorts; one training set (N = 227) and three validation cohorts (N = 137, N = 201, N = 76) from 2 institutions, we show that the automated TIL scoring algorithm separates patients into favorable and poor prognosis cohorts, where higher TILs scores were associated with favorable prognosis. In multivariable analyses, automated TIL scores show an independent association with disease-specific overall survival. Therefore, the open source, automated TIL scoring is an independent prognostic marker in melanoma. With further study, we believe that this algorithm could be useful to define a subset of patients that could potentially be spared immunotherapy.

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MR‐Imaging enables accurate diagnosis and follow‐up for vitrectomized eyes in uveal melanoma patients

Acta Ophthalmologica ◽

10.1111/aos.13972_199 ◽

2018 ◽

Vol 96 (S261) ◽

pp. 56-56

Keyword(s):

Mr Imaging ◽

Uveal Melanoma ◽

Accurate Diagnosis ◽

Melanoma Patients

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Multiparameter study of the immunophenotype of tumor infiltrating lymphocytes, in cancer patients

Russian Journal of Oncology ◽

10.18821/1028-9984-2015-21-1-51-54 ◽

2016 ◽

Vol 21 (1-2) ◽

pp. 51-54 ◽

Cited By ~ 1

Author(s):

Tat’yana N. Zabotina ◽

O. V Korotkova ◽

A. A Borunova ◽

D. V Tabakov ◽

I. I Bokin ◽

...

Keyword(s):

Flow Cytometry ◽

Solid Tumors ◽

Squamous Carcinoma ◽

Tumor Infiltrating Lymphocytes ◽

Tissue Level ◽

Main Role ◽

Regulatory T Lymphocytes ◽

The Difference ◽

Infiltrating Lymphocytes ◽

First Time

For the first time in Russia the immunophenotype of tumor infiltrated lymphocytes (TIL) was investigated with the use of a method of quantitative flow cytometry. Samples from 104 patients, suffering from solid tumors (such as breast cancer, ovarian cancer, melanoma and oral cavity squamous carcinoma), were analyzed in this investigation. In the difference of cytomorphological analysis, the method of flow cytometry identified TIL in 100% of cases. In the structure of CDS+Т- lymphocytes the ratio CD4/CD8 was equal to 1,1±0,1. Serial gating strategy allowed to assess minor subpopulations of regulatory T-lymphocytes CD45+CD4+CD127+low/neg and CD45+CD8+CD28-CD11b-. Regulatory mechanisms with involvement of CD8 T-cells played the main role in the generation of immune responses at the tissue level ofpatients, suffering from solid tumors, independent of nosological form of disease.

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