المؤلفون: Femel, Julia, Hill, Cameron, Illa Bochaca, Irineu, Booth, Jamie L., Asnaashari, Tina G., Steele, Maria M., Moshiri, Ata S., Hyungrok Do, Zhong, Judy, Osman, Iman, Leachman, Sancy A., Takahiro Tsujikawa, White, Kevin P., Chang, Young H., Lund, Amanda W.

المصدر: Frontiers in Immunology; 2024, p1-11, 13p

مصطلحات موضوعية: MELANOMA, PROGNOSIS, IMMUNOHISTOCHEMISTRY, HETEROGENEITY

مستخلص: Introduction: Quantitative, multiplexed imaging is revealing complex spatial relationships between phenotypically diverse tumor infiltrating leukocyte populations and their prognostic implications. The underlying mechanisms and tissue structures that determine leukocyte distribution within and around tumor nests, however, remain poorly understood. While presumed players in metastatic dissemination, new preclinical data demonstrates that blood and lymphatic vessels (lymphovasculature) also dictate leukocyte trafficking within tumor microenvironments and thereby impact anti-tumor immunity. Here we interrogate these relationships in primary human cutaneous melanoma. Methods: We established a quantitative, multiplexed imaging platform to simultaneously detect immune infiltrates and tumor-associated vessels in formalin-fixed paraffin embedded patient samples. We performed a discovery, retrospective analysis of 28 treatment-naïve, primary cutaneous melanomas. Results: Here we find that the lymphvasculature and immune infiltrate is heterogenous across patients in treatment naïve, primary melanoma. We categorized five lymphovascular subtypes that differ by functionality and morphology and mapped their localization in and around primary tumors. Interestingly, the localization of specific vessel subtypes, but not overall vessel density, significantly associated with the presence of lymphoid aggregates, regional progression, and intratumoral T cell infiltrates. Discussion: We describe a quantitative platform to enable simultaneous lymphovascular and immune infiltrate analysis and map their spatial relationships in primary melanoma. Our data indicate that tumor-associated vessels exist in different states and that their localization may determine potential for metastasis or immune infiltration. This platform will support future efforts to map tumor-associated lymphovascular evolution across stage, assess its prognostic value, and stratify patients for adjuvant therapy. [ABSTRACT FROM AUTHOR]

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المؤلفون: Bajaj, Shirin, Donnelly, Douglas, Call, Melissa, Johannet, Paul, Moran, Una, Polsky, David, Shapiro, Richard, Berman, Russell, Pavlick, Anna, Weber, Jeffrey, Zhong, Judy, Osman, Iman

المصدر: JNCI: Journal of the National Cancer Institute; Sep2020, Vol. 112 Issue 9, p921-928, 8p

مصطلحات موضوعية: TUMOR classification, MELANOMA, LOG-rank test, PROGNOSIS, DISEASE progression, MELANOMA diagnosis, MELANOMA treatment, RESEARCH, RESEARCH evaluation, PREDICTIVE tests, RESEARCH methodology, METASTASIS, MEDICAL cooperation, EVALUATION research, MEDICAL protocols, SKIN tumors, COMPARATIVE studies, RESEARCH funding, ONCOLOGY, MEDICAL societies, LONGITUDINAL method, STANDARDS

مصطلحات جغرافية: UNITED States

مستخلص: Background: The American Joint Committee on Cancer (AJCC) maintains that the eighth edition of its Staging Manual (AJCC8) has improved accuracy compared with the seventh (AJCC7). However, there are concerns that implementation may disrupt analysis of active clinical trials for stage III patients. We used an independent cohort of melanoma patients to test the extent to which AJCC8 has improved prognostic accuracy compared with AJCC7.Methods: We analyzed a cohort of 1315 prospectively enrolled patients. We assessed primary tumor and nodal classification of stage I-III patients using AJCC7 and AJCC8 to assign disease stages at diagnosis. We compared recurrence-free (RFS) and overall survival (OS) using Kaplan-Meier curves and log-rank tests. We then compared concordance indices of discriminatory prognostic ability and area under the curve of 5-year survival to predict RFS and OS. All statistical tests were two-sided.Results: Stage IIC patients continued to have worse outcomes than stage IIIA patients, with a 5-year RFS of 26.5% (95% confidence interval [CI] = 12.8% to 55.1%) vs 56.0% (95% CI = 37.0% to 84.7%) by AJCC8 (P = .002). For stage I, removing mitotic index as a T classification factor decreased its prognostic value, although not statistically significantly (RFS concordance index [C-index] = 0.63, 95% CI = 0.56 to 0.69; to 0.56, 95% CI = 0.49 to 0.63, P = .07; OS C-index = 0.48, 95% CI = 0.38 to 0.58; to 0.48, 95% CI = 0.41 to 0.56, P = .90). For stage II, prognostication remained constant (RFS C-index = 0.65, 95% CI = 0.57 to 0.72; OS C-index = 0.61, 95% CI = 0.50 to 0.72), and for stage III, AJCC8 yielded statistically significantly enhanced prognostication for RFS (C-index = 0.65, 95% CI = 0.60 to 0.70; to 0.70, 95% CI = 0.66 to 0.75, P = .01).Conclusions: Compared with AJCC7, we demonstrate that AJCC8 enables more accurate prognosis for patients with stage III melanoma. Restaging a large cohort of patients can enhance the analysis of active clinical trials. [ABSTRACT FROM AUTHOR]

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المؤلفون: Weiss, Sarah, Hanniford, Douglas, Hernando, Eva, Osman, Iman

مصطلحات موضوعية: Skin Neoplasms, Biomarkers, Tumor, Humans, Prognosis, Melanoma, Survival Analysis, Article, Neoplasm Staging

الوصف: The American Joint Committee on Cancer staging system for cutaneous melanoma is based on primary tumor thickness and the presence of ulceration, mitoses, lymph node spread, and distant metastases as determinants of prognosis. Although this cutaneous melanoma staging system has evolved over time to more accurately reflect patient prognosis, improvements are still needed, because current understanding of the particular factors (genetic mutation, expression alteration, host response, etc) that are critical for predicting patient outcomes is incomplete. Given the clinical and biologic heterogeneity of primary melanomas, new prognostic tools are needed to more precisely identify patients who are most likely to develop advanced disease. Such tools would affect clinical surveillance strategies and aid in patient selection for adjuvant therapy. The authors reviewed the literature on prognostic molecular and immunologic markers in primary cutaneous melanoma, their associations with clinicopathologic and survival outcomes, and their potential for incorporation into current staging models. Overall, the studies considered in this review did not define prognostic markers that could be readily incorporated into the current staging system. Therefore, efforts should be continued in these and other directions to maximize the likelihood of identifying clinically useful prognostic biomarkers for cutaneous melanoma.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::fca72982c64ff2ecbb2b1096523ee0c9Test
https://europepmc.org/articles/PMC4666819Test/

المؤلفون: Weiss, Sarah A., Hanniford, Douglas, Hernando, Eva, Osman, Iman

المصدر: Cancer (0008543X); Dec2015, Vol. 121 Issue 23, p4108-4123, 16p

مصطلحات موضوعية: SKIN cancer, SKIN cancer patients, CANCER treatment, ADJUVANT treatment of cancer, GENETIC mutation, HEALTH outcome assessment, PROGNOSIS, MELANOMA, RESEARCH funding, SKIN tumors, SURVIVAL analysis (Biometry), TUMOR classification

مستخلص: The American Joint Committee on Cancer staging system for cutaneous melanoma is based on primary tumor thickness and the presence of ulceration, mitoses, lymph node spread, and distant metastases as determinants of prognosis. Although this cutaneous melanoma staging system has evolved over time to more accurately reflect patient prognosis, improvements are still needed, because current understanding of the particular factors (genetic mutation, expression alteration, host response, etc) that are critical for predicting patient outcomes is incomplete. Given the clinical and biologic heterogeneity of primary melanomas, new prognostic tools are needed to more precisely identify patients who are most likely to develop advanced disease. Such tools would affect clinical surveillance strategies and aid in patient selection for adjuvant therapy. The authors reviewed the literature on prognostic molecular and immunologic markers in primary cutaneous melanoma, their associations with clinicopathologic and survival outcomes, and their potential for incorporation into current staging models. Overall, the studies considered in this review did not define prognostic markers that could be readily incorporated into the current staging system. Therefore, efforts should be continued in these and other directions to maximize the likelihood of identifying clinically useful prognostic biomarkers for cutaneous melanoma. [ABSTRACT FROM AUTHOR]

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المؤلفون: Weiss, Sarah, Darvishian, Farbod, Tadepalli, Jyothi, Shapiro, Richard, Golfinos, John, Pavlick, Anna, Polsky, David, Kirchhoff, Tomas, Osman, Iman

المصدر: BMC Cancer; 11/23/2015, Vol. 15, p1-6, 6p, 2 Color Photographs, 1 Black and White Photograph, 1 Chart, 1 Graph

مصطلحات موضوعية: MELANOMA treatment, BRAIN metastasis, SOMATIC cells, GERM cells, CANCER relapse, HEALTH outcome assessment, THERAPEUTICS, BRAIN tumors, HYDROLASES, MELANOMA, MEMBRANE proteins, GENETIC mutation, PROGNOSIS, RESEARCH funding, TRANSFERASES

مستخلص: Background: Median overall survival (OS) of patients with melanoma brain metastases (MBM) is usually 6 months or less. There are rare reports of patients with treated MBM who survived for years. These outlier cases represent valuable opportunities to study the somatic and germline factors that may have influenced patient outcome and led to extended survival.Case Presentation: Here we report the clinical scenario of a 67 year old man with a recurrent brain metastasis from melanoma who has survived over 12 years post-resection. We review the literature relating to clinical and molecular variables associated with long term survival post-brain metastasis. We present the somatic characteristics of this individual patient's tumor as well as an analysis of inherited genetic variants related to immune function. The patient's resected brain tumor is BRAF V600E mutated, NRAS wild type (WT), and TERT C250T mutated. The patient is a carrier of germline variants in immunomodulatory loci associated with prolonged survival.Conclusions: Our data suggest that genetic variants in immunomodulatory loci may partially contribute to this patient's unusually favorable outcome and should not be overlooked. With further and future investigation, knowledge of inherited single nucleotide polymorphisms (SNPs) may provide clinicians with more individualized prognostic information for melanoma patients, with potential implications for surveillance strategies and therapeutic interventions. [ABSTRACT FROM AUTHOR]

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المؤلفون: Tu, Ting J., Ma, Michelle W., Monni, Stefano, Rose, Amy E., Yee, Herman, Darvishian, Farbod, Polsky, David, Berman, Russell S., Shapiro, Richard L., Pavlick, Anna C., Mazumdar, Madhu, Osman, Iman

المصدر: Oncology; 2011, Vol. 80 Issue 3/4, p181-187, 7p, 1 Color Photograph, 4 Charts

مصطلحات موضوعية: MELANOMA, PROGNOSIS, ANTIGENS, TUMORS, NEUROENDOCRINE tumors

مستخلص: Objective: Previous melanoma studies evaluating prognostic factors of survival at recurrence have focused on primary tumor characteristics and clinical variables at first recurrence. We examined the prognostic relevance of recurrent tumor proliferation. Methods: 114 melanoma patients with available recurrent tissues who were prospectively enrolled at New York University Medical Center were studied. Standard of care prognostic variables (e.g. stage at initial diagnosis and lactate dehydrogenase level) and recurrent tissue expression of proliferative marker Ki-67 were evaluated for their association with overall survival. Results: High Ki-67 expression was observed in 57 (50%) of the 114 recurrent melanomas. On univariate analysis, the median overall survival of patients whose recurrent tumors overexpressed Ki-67 was significantly shorter than that of patients whose recurrent tumors had low Ki-67 expression (3.6 vs. 9.5 years, p = 0.03). On multivariate analysis, a high proliferative index of the recurrent melanoma remained an independent predictor of worse overall survival, controlling for stage at initial diagnosis, disease-free survival, and stage at first recurrence [HR = 2.09 (95% CI 1.24-3.54), p = 0.006]. Conclusions: Our results demonstrate the prognostic relevance of tumor proliferation in recurrent melanoma patients. Data also support restratification of risk assessment upon recurrence that considers tumor biology in addition to clinical variables evaluated as part of the standard of care. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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المؤلفون: Chang, David Z., Panageas, Katherine S., Osman, Iman, Polsky, David, Busam, Klaus, Chapman, Paul B.

المصدر: Journal of Translational Medicine; 2004, Vol. 2, p1-5, 5p

مصطلحات موضوعية: MELANOMA, NEUROENDOCRINE tumors, GENETIC mutation, METASTASIS, PROGNOSIS, CLINICAL trials

مستخلص: Forty to eighty percent of melanoma tumors have activating mutations in BRAF although the clinical importance of these mutations is not clear. We previously reported an analysis of BRAF mutations in metastatic melanoma samples from 68 patients. In this study, we correlated patient baseline characteristics, prognostic factors, and/or clinical outcomes with the presence of BRAF mutations. No significant differences were observed in age, gender, location of primary melanoma, stage at the diagnosis, and depth of primary tumor between patients with and without BRAF mutations. Melanomas harboring BRAF mutations were more likely to metastasize to liver (P = 0.02) and to metastasize to multiple organs (P = 0.048). Neither time to progression to stage IV nor overall survival were associated with BRAF mutations. In conclusion, we observed no significant differences in clinical characteristics or outcomes between melanomas with or without BRAF mutations. Although there was an increased frequency of liver metastasis and tendency to metastasize to multiple organs in tumors with BRAF mutations, there was no detectable effect on survival. Future prospective studies should include analysis of whether BRAF mutations in melanoma tumors correlate with an increased tendency to metastasize to liver or to multiple organs. [ABSTRACT FROM AUTHOR]

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المؤلفون: Polsky, David, Melzer, Kate, Hazan, Carole, Panageas, Katherine S., Busam, Klaus, Drobnjak, Maria, Kamino, Hideko, Spira, Joanna G., Kopf, Alfred W., Houghton, Alan, Cordon-Cardo, Carlos, Osman, Iman

المصدر: JNCI: Journal of the National Cancer Institute; 12/4/2002, Vol. 94 Issue 23, p1803-1806, 4p, 2 Color Photographs, 2 Charts, 2 Graphs

مصطلحات موضوعية: ONCOGENES, PROGNOSIS

مستخلص: Overexpression of the oncogene HDM2 is observed in a substantial proportion of melanomas, including noninvasive and thin lesions, suggesting that HDM2 overexpression may be an early event in melanocyte transformation. To determine the role of HDM2 in the clinical progression of melanoma, we examined whether its expression was associated with patient survival. From November 1972 through November 1982, 134 patients with melanoma who participated in the New York University Melanoma Cooperative Group were studied, if representative tissues and follow-up were available. HDM2 protein expression was assessed immunohistochemically. Unexpectedly, we observed that HDM2 overexpression was statistically significantly associated with improved disease-free survival (relative risk [RR] = 0.47, 95% confidence interval [CI] = 0.24 to 0.89; two-sided chi(2) P =.021) and overall survival (RR = 0.55, 95% CI = 0.33 to 0.94; two-sided chi(2) P =.027) in multivariable analysis. HDM2 overexpression appears to be an independent predictor of survival for patients with primary melanoma; however, larger prospective studies are required for validation. [ABSTRACT FROM AUTHOR]

: Copyright of JNCI: Journal of the National Cancer Institute is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)