Prognostic immunohistochemical markers of primary human melanomas

Ostmeier, H.; Fuchs, Blandine; Otto, F.; Mawick, R; Lippold, A.; Krieg, V.; Suter, L.

doi:10.1046/j.1365-2133.2001.04335.x

Cited by 53 publications

(36 citation statements)

References 45 publications

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“…5 In human melanoma, M-CAM expression is associated with tumor progression, possibly through enhanced interaction between melanoma and endothelial cells, 8,9 and to poor prognosis, although it is not independent of other biological markers such as Ki67 labeling. 10 A correlation between M-CAM upregulation and tumor progression has also been reported for prostate cancer.…”

Section: Discussionmentioning

confidence: 97%

“…Although the physiological ligand has not yet been identified and the biological role of M-CAM in normal tissue and malignant tumors remains unclear, M-CAM has been suggested to play an important role in implantation and placentation during embryogenesis and in tumor progression. 6 M-CAM expression can promote tumor progression and is associated with poor prognosis in melanoma, [8][9][10] prostate cancer 11,12 and in pulmonary adenocarcinomas. 13 Here, we show on in vitro samples that M-CAM is expressed on EOC and that its expression seems related to ovarian tumor progression.…”

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confidence: 99%

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M‐CAM expression as marker of poor prognosis in epithelial ovarian cancer

Aldovini

Demichelis²,

Doglioni³

et al. 2006

Intl Journal of Cancer

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Currently available clinico–pathologic criteria provide an imperfect assessment of outcome for patients with advanced epithelial ovarian cancer (EOC). Identification of prognostic factors related to tumor biology might improve this assessment. We investigated the prognostic significance of the melanoma cell adhesion molecule (M‐CAM) in EOC. Using the same antibody, M‐CAM expression was tested by Western blotting in protein extracts and by immunohistochemestry in tissue microarrays generated from 133 consecutively resected, well characterized EOC samples. Fisher test, Kaplan–Meier method and Cox proportional hazards analysis were used to relate M‐CAM expression to clinico–pathological variables and to time to progression (TTP) and overall survival (OS). In vitro biochemical analysis showed a progressively increased M‐CAM expression from normal to malignant cells. M‐CAM protein, detected immunohistochemically, was significantly associated with advanced tumor stage, serous and undifferentiated histotype, extent of residual disease and p53 accumulation. Presence or absence of M‐CAM significantly divided patients according to their TTP (median, 22 vs. 79 months, respectively; log‐rank p = 0.001) and OS (median, 42 vs. 131 months, respectively; log‐rank p = 0.0003). In the subgroup of advanced stage patients who achieved complete response after front‐line treatment, M‐CAM expression and absence of residual disease were significantly associated with shorter TTP (p = 0.003, HR 5.25, 95% Cl 1.79–15.41 and p = 0.011, HR 3.77, 95% Cl 1.36–10.49 respectively) at the multivariate level. In the same sub‐group of patients, M‐CAM expression remained the only parameter significantly associated with OS (p = 0.005, HR 3.35, 95% Cl 1.42–6.88). M‐CAM is a marker of early relapse and poorer outcome in EOC. In particular, M‐CAM expression identifies a subgroup of front‐line therapy‐responding patients who undergo dramatic relapses, thus helping to better select patients who might benefit from new/alternative therapeutic modalities. © 2006 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

M‐CAM expression as marker of poor prognosis in epithelial ovarian cancer

Aldovini

Demichelis²,

Doglioni³

et al. 2006

Intl Journal of Cancer

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“…On one hand, our results provide evidence that our previously reported MHC II-mediated hampering of the killing by immune cells is physiologically valid. On the other hand, they may provide one possible explanation into the growth advantage of MHC II-positive skin tumors (50) and into the longstanding correlation between MHC II expression and degree of melanoma malignancy (2,(5)(6)(7). However LAG-3 also protects from drug-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

MHC Class II Engagement by Its Ligand LAG-3 (CD223) Contributes to Melanoma Resistance to Apoptosis

Hémon

Jean-Louis

Ramgolam

et al. 2011

The Journal of Immunology

216

146

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Melanoma is the most aggressive skin cancer in humans that often expresses MHC class II (MHC II) molecules, which could make these tumors eliminable by the immune system. However, this MHC II expression has been associated with poor prognosis, and there is a lack of immune-mediated eradication. The lymphocyte activation gene-3 (LAG-3) is a natural ligand for MHC II that is substantially expressed on melanoma-infiltrating T cells including those endowed with potent immune-suppressive activity. Based on our previous data showing the signaling capacity of MHC II in melanoma cells, we hypothesized that LAG-3 could contribute to melanoma survival through its MHC II signaling capacity in melanoma cells. In this study, we demonstrate that both soluble LAG-3 and LAG-3–transfected cells can protect MHC II-positive melanoma cells, but not MHC II-negative cells, from FAS-mediated and drug-induced apoptosis. Interaction of LAG-3 with MHC II expressed on melanoma cells upregulates both MAPK/Erk and PI3K/Akt pathways, albeit with different kinetics. Inhibition studies using specific inhibitors of both pathways provided evidence of their involvement in the LAG-3–induced protection from apoptosis. Altogether, our data suggest that the LAG-3–MHC II interaction could be viewed as a bidirectional immune escape pathway in melanoma, with direct consequences shared by both melanoma and immune cells. In the future, compounds that efficiently hinder LAG-3–MHC II interaction might be used as an adjuvant to current therapy for MHC II-positive melanoma.

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“…It should be noted, however, that although these mRNA data are supportive of active gene transcription, one could not conclude that the encoded proteins are properly translated, proteolytically processed and correctly oriented within the cell, which is of key importance to effective antigen presentation (York and Rock, 1996). Another peculiarity of some human melanoma cells is their ability to constitutively express MHCII and this is often associated with a poor prognosis (D'Alessandro et al, 1987;Martins et al, 2009;Ostmeier et al, 2001). Immune escape mediated by this alteration has been proposed as a possible explanation for worsening of the tumour phenotype (Aoudjit et al, 2004).…”

Section: Possible Immunological Reasons For Lack Of Efficacymentioning

confidence: 99%

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

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Canine melanoma as a model of human melanomaFor at least two decades, veterinary oncologists have advocated using spontaneously occurring tumours in companion animals as models for human cancer (Knapp and Waters, 1997;MacEwen, 1990). Several recent reviews have readdressed this approach identifying osteosarcoma, mammary tumours, head and neck cancers, bladder carcinomas, non-Hodgkin lymphoma, prostatic carcinoma, lung cancer and pertinently oral canine malignant melanoma (CMM) as good models for human neoplasms (Hansen and Khanna, 2004;Khanna and Hunter, 2005;Paoloni and Khanna, 2008). The major benefits of dogs as tumour models include the ability to study genetically outbred and immunologically intact animals in which cancers develop spontaneously and thus, more likely reflect the process of tumourigenesis compared to experimentally-induced neoplasms. As pets and owners share the same environment, they may be exposed to the same carcinogens, which, in part, drive tumour development. Regarding disease modelling, animal tumours often have similar clinical presentation, tumour biology and histopathological appearance to their human counterparts and usually progress more rapidly, thereby shortening data maturation times. In addition, few "standard of care" therapies exist for dogs meaning that within reason, trial therapeutics can be instigated at any point. Given these benefits, companion animal tumour models more accurately reflect the features of human cancers compared to rodent models with CMM being a desirable example of one such neoplasm. Conversely, the opportunity to translate the potential value of state of the art human therapeutics to the veterinary clinic also exists. Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics.

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Prognostic immunohistochemical markers of primary human melanomas

Abstract: Ki-67 and HLA-DQ may be useful for risk assessments in primary melanomas.

Cited by 53 publications

References 45 publications

M‐CAM expression as marker of poor prognosis in epithelial ovarian cancer

M‐CAM expression as marker of poor prognosis in epithelial ovarian cancer

MHC Class II Engagement by Its Ligand LAG-3 (CD223) Contributes to Melanoma Resistance to Apoptosis

Cancer immunology and canine malignant melanoma: A comparative review

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