scholarly journals Serum CEACAM1 Correlates with Disease Progression and Survival in Malignant Melanoma Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Sapoznik Sivan ◽  
Faranesh Suzan ◽  
Ortenberg Rona ◽  
Hamburger Tamar ◽  
Barak Vivian ◽  
...  

The search for melanoma biomarkers is crucial, as the incidence of melanoma continues to rise. We have previously demonstrated that serum CEACAM1 (sCEACAM1) is secreted from melanoma cells and correlates with disease progression in metastatic melanoma patients. Here, we have used a different cohort of melanoma patients with regional or metastatic disease (N=49), treated with autologous vaccination. By monitoring sCEACAM1 in serum samples obtained prior to and after vaccination, we show that sCEACAM1 correlates with disease state, overall survival, and S100B. The trend of change in sCEACAM1 following vaccination (increase/decrease) inversely correlates with overall survival. DTH skin test is used to evaluate patients’ anti-melanoma immune response and to predict response to vaccination. Importantly, sCEACAM1 had a stronger prognostic value than that of DTH, and when sCEACAM1 decreased following treatment, this was the dominant predictor of increased survival. Collectively, our results point out the relevance of sCEACAM1 in monitoring melanoma patients.

2019 ◽  
Vol 11 ◽  
pp. 175883591984887 ◽  
Author(s):  
Lorena Incorvaia ◽  
Giuseppe Badalamenti ◽  
Gaetana Rinaldi ◽  
Juan Lucio Iovanna ◽  
Daniel Olive ◽  
...  

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.


2009 ◽  
Vol 27 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Mercedes N. López ◽  
Cristian Pereda ◽  
Gabriela Segal ◽  
Leonel Muñoz ◽  
Raquel Aguilera ◽  
...  

PurposeThe aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines.Patients and MethodsForty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records.ResultsThe overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) β+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001).ConclusionOur findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFβ+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18009-18009
Author(s):  
P. A. Ascierto ◽  
M. Budroni ◽  
A. Cossu ◽  
S. Scala ◽  
E. Simeone ◽  
...  

18009 Background: Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). Methods: One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Results: Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (≥2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Conclusions: Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease. No significant financial relationships to disclose.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21512-e21512
Author(s):  
Oliver Oey ◽  
Muhammad Adnan Khattak ◽  
Afaf Abed ◽  
Tarek Meniawy ◽  
Anna Reid ◽  
...  

e21512 Background: Anti-PD-1 therapy has improved the outcome of advanced melanoma patients with a 5-year survival rate of about 40-45%. However, biomarkers predictive of response to immune checkpoint blockade therapy are lacking. There is limited data on the utility of host germline human leucocyte antigen (HLA) genotype as a predictor of response to anti-PD-1 therapy in advanced melanoma. Here, we investigate the prognostic value of HLA in predicting survival outcomes of patients with unresectable locally advanced, metastatic melanoma on anti-PD-1 therapy. Methods: Blood was collected from 113 metastatic melanoma patients who were treated with anti-PD-1 therapy at two major oncology centres in Western Australia. High quality DNA was extracted from white blood cells and subsequently HLA-I and HLA-II typed using clinically validated assay. Univariate analyses were conducted using Cox regression model correlating homozygosity at HLA-I and HLA-II loci with overall survival (OS). HLA-A and HLA-B were classified into 12 supertypes and correlated with OS. Multivariate analyses were performed while controlling for age, gender, prior therapy, BRAF mutation status, ECOG performance status and presence of liver and brain metastases. Results: Homozygosity at HLA-I or HLA-II loci was not associated with OS. However, the absence of HLA-B62 supertype was associated with a trend towards improved OS (HR: 0.53 [95% CI:0.25-1.10]; P = 0.09) as reported previously. Notably, the absence of HLA-B27 supertype was associated with improved OS which was statistically significant (HR: 0.45 [95% CI:0.24-0.85]; P = 0.01). In multivariate analyses, the prognostic value of HLA-B27 supertype (HR: 0.38 [95% CI:0.19-0.76]; P = 0.006) was maintained, whereas the prognostic value of HLA-B62 supertype significantly improved (HR: 0.42 [95% CI:0.19-0.94]; P = 0.03). Conclusions: Our results suggest a limited role of HLA homozygosity in predicting survival of melanoma patients treated with anti-PD-1 therapy. However, we identified that the absence of HLA-B62 and HLA-B27 supertype is associated with improved survival benefit. Therefore, HLA-B27 and HLA-B62 supertype may be used as adjunct biomarkers of response to anti-PD-1 therapy in patients with melanoma in addition to PD-L1 status, pending validation in prospective randomised clinical trials.


2015 ◽  
Vol 75 (23) ◽  
pp. 5084-5092 ◽  
Author(s):  
Yoshinobu Koguchi ◽  
Helena M. Hoen ◽  
Shelly A. Bambina ◽  
Michael D. Rynning ◽  
Richard K. Fuerstenberg ◽  
...  

2010 ◽  
Vol 130 (10) ◽  
pp. 2514-2516 ◽  
Author(s):  
Christian Busch ◽  
Jürgen Geisler ◽  
Stian Knappskog ◽  
Johan R. Lillehaug ◽  
Per E. Lønning

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8540-8540 ◽  
Author(s):  
R. Mouawad ◽  
C. Soubrane ◽  
D. Khayat

8540 Background and aims: Circulating vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) were described as prognostic factors in several cancers. The aim of this study is to evaluate the prognostic values of these parameters in metastatic malignant melanoma diseases. Methods and Patients: Using enzyme-linked immunosorbent assays, VEGFs (A, C, D) and their receptors (1, 2, and 3) were measured in sera of 75 patients with metastatic malignant melanoma in comparison to 30 healthy controls. Disease free survival (DFS) and overall survival (OS) were calculated from the beginning of the treatment until either the progression or the death and analyzed using the Kaplan-Meier method. Results: Pretreatment median sVEGF-A, sVEGF-C as well as VEGFR-3 levels were significantly higher in MMM patients as compared to healthy ones p=0.0017, p=0.005, p<0.00001 respectively). None of the studied markers correlated with gender, age or LDH levels. An inverse correlation between soluble VEGFR-2 and VEGF-D levels was observed (r=−0.33 p=0.040). High soluble VEGF-C and VEGFR-3 were correlated to high tumor burden (p=0.02, p=0.045). However, a relationship with lymph node metastasis was observed with sVEGF-A but not with sVEGFR-3. As shown by univariate analysis, only elevated levels of sVEGF-R1 concentration were found to exert a significantly unfavorable impact on both disease-free (χ2=6.64, p= 0.014) and overall survival (χ2=8.03, p= 0.0046). Conclusions: Our results suggest that, in metastatic malignant melanoma patients, soluble VEGF-A and VEGF-R3 pretreatment levels may prospectively identify high-risk patients with a worse prognosis; serum VEGFR-1 level may be a predictive factor of time to progression and overall survival. A multivariate analysis (Cox test) is ongoing in order to confirm if this parameter is an independent prognostic factor. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24055-e24055
Author(s):  
Benjamin Switzer ◽  
David James Savage ◽  
Jung Min Song ◽  
Carolyn Stanek ◽  
Pauline Funchain

e24055 Background: Despite an encouraging 99% five-year survival in patients diagnosed with early-stage melanoma, a higher proportion of fatal melanomas initially present with thin ( < 1mm) rather than thick ( > 4mm) melanoma.1 Therefore, early-stage melanoma survivorship remains a topic of high interest. We examined a cohort of early-stage melanomas which progressed to stage IV to inform survivorship and risk-stratification approaches in this large, understudied population. Methods: From a retrospective single-center study of 880 consecutive melanoma patients from 2016-2020, we identified new, non- de novo diagnoses of stage IV melanoma which progressed from an initial early-stage (IA-IIA) diagnosis. Descriptive data were collected via chart review on demographics, clinical features, presentation at time of progression, and follow up prior to progression. Results: A total of 50 patients met the inclusion criterion of an initial stage IA-IIA diagnosis with subsequent progression to stage IV melanoma. Primary early stage melanomas were diagnosed an average of 6.1 years prior to metastatic disease progression, with 46% (n = 23) diagnosed within 3 years, 22% (n = 11) between 4-6 years, 12% (n = 6) between 7-10 years, 8% (n = 4) between 10-12 years, and 12% (n = 6) beyond the 12 year mark from their initial early-stage diagnosis. Average age at time of diagnosis was 57.7 (median 60, range 21-68), and 62% (n = 31) were male. The two most common early-stage diagnostic sites were lower extremities (27.5%, n = 14) and back (23.5%, n = 12). The two most common sites of metastatic disease were lung (46%, n = 23) and brain (28%, n = 14). A total of 30% (n = 15) and 34% (n = 17) of this cohort maintained follow up with oncology and dermatology, respectively, prior to their stage IV diagnosis. Symptomatic disease lead to 80% (n = 40) of stage IV diagnoses, while 14% (n = 7) were diagnosed through routine oncologic or dermatologic follow up, and the final 6% were diagnosed incidentally. Conclusions: Early stage melanoma patients who develop stage IV disease exhibit wide ranges in onset of disease progression, thus survivorship plans for this group could include a combination of early provider screening and patient education for later presentations of metastatic disease. Due to relatively common metastatic involvement of the lung and brain, a high suspicion to screen for metastatic disease with symptoms involving these organs may be appropriate.


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