Expression of Fas and Fas ligand in uveal melanoma: biological implication and prognostic value

Anastassiou, Gerasimos; Coupland, Sarah E.; Stang, Andreas; Boeloeni, Reka; Schilling, Hannah; Bornfeld, Norbert

doi:10.1002/path.926

Cited by 25 publications

(33 citation statements)

References 35 publications

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“…It has been recently demonstrated that UMM cells produce soluble FasL that binds to the surface of neoplastic cells, protecting them from Fas-induced cell death (49). Anastiassiou et al (12) showed FasL expression in most of 103 clinically wellcharacterized cases of UMM. These authors, however, did not find a decreased number of TIL in FasL expressing tumors, as had been expected based on the data published on other FasL positive tumors inducing apoptosis of the Fas-positive leukocytes (50).…”

Section: Discussionmentioning

confidence: 99%

Tumor Infiltrating Lymphocytes in Uveal Melanoma: A Link with Clinical Behavior?

Staibano¹,

Mascolo²,

Tranfa

et al. 2006

Int J Immunopathol Pharmacol

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Experimental and clinical evidence indicate that immunological mechanisms might be important in the clinical course of uveal malignant melanoma (UMM). We analyzed the amount and phenotype of tumor infiltrating lymphocytes (TIL) and the expression of the apoptosis-inducing molecule Fas and its ligand, FasL, on tumor cells and TIL in a selected series of UMM with the aim to establish if a correlation between their expression and the clinical behavior of UMM exists. TIL phenotype and Fas/FasL expression were evaluated by immunohistochemistry in 61 cases of formalin-fixed, paraffin-embedded UMM. Results were compared with the follow-up data of patients. Most of the UMM showed a prevalence of CD8+ CD3+ T lymphocytes, or CD4+ and CD8+ cells in equal amounts. UMM showed a variable expression of FasL, ranging from 0 to > 40% of neoplastic cells. Fas was always expressed in TIL, although with a variable extent. A subgroup of UMM showed in TIL a strongly reduced or even absent expression ofTCR~-chain, involved in activation ofT-lymphocytes. This subgroup was characterized by a worse outcome. We hypothesized that an impaired cytotoxic immune response due to the loss of the~ chain expression plays a primary role in the biological course of UMM. Our results indicate that the overcoming of the impairment of TCR function may represent a prerequisite for the development of new therapeutic strategies for managing UMM, suggesting that elimination of tumor cells may be possible by activation of cytotoxic cells present within ocular melanomas.Uveal malignant melanoma (UMM) is the most common malignant primary intra-ocular tumor in adults (1-4). It accounts for 70-88% of all ocular tumors, with an annual incidence of approximately 6 cases per milIion per year (1-4). The therapy of UMM is problematic due to the high rate of metastatic dissemination (5). Treatment therapies for this tumor warrant further studies. To date, enucleation remains as effective as the recent eyesparing approaches (6-7). When metastatic disease is diagnosed, patient survival is generally less than 7 months (8-11). During the "dormant" period from diagnosis of primitive tumor and the occurrence of metastasis, chemo-and immunotherapy have also been considered (12).UMM arises in the immune-privileged ocular

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Section: Discussionmentioning

confidence: 99%

Tumor Infiltrating Lymphocytes in Uveal Melanoma: A Link with Clinical Behavior?

Staibano¹,

Mascolo²,

Tranfa

et al. 2006

Int J Immunopathol Pharmacol

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“…Recently, it has been demonstrated that increased soluble Fas/CD95 serum levels correlate with poor prognosis in melanoma patients [17]. In uveal melanoma, metastasisfree 5-year survival rates were considerably lower in patients with tumors that lacked FasL/CD95L expression [18]. In the present study, immunohistochemistry was used to examine Fas/CD95 and FasL/CD95L expression in pathologically and clinically well-characterized cases of cutaneous malignant melanoma.…”

Section: Introductionmentioning

confidence: 90%

Expression of Fas Ligand (CD95L) in Primary Malignant Melanoma and Melanoma Metastases is Associated with Overall Survival

Neuber¹,

Eidam²

2006

Oncol Res Treat

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Background: There is increasing evidence that the Fas/Fas ligand (FasL) system is involved in tumor-mediated immune suppression. The purpose of this study was to investigate the effect of Fas (CD95) as well as FasL (CD95L) expression in primary malignant melanoma and melanoma metastases on overall survival (OS). Patients and Methods: 19 patients with metastatic malignant melanoma who were treated with different dacarbazine (DTIC)-based chemotherapy regimens were included in this study. From each patient, primary melanoma biopsies and biopsies from metastases were histologically evaluated. Immunohistology was performed with antibodies to Fas/CD95 and FasL/CD95L. Differences in OS were plotted using the Kaplan-Meier method and compared by the log rank test. Results: Fas/CD95 and FasL/CD95L expression was detected in 73.7 and 63.2% of primary melanomas, respectively. In metastases, expression of both Fas/CD95 (63.2%) and FasL/CD95L (47.4%) was markedly decreased. Presence of FasL/ CD95L expression in primary melanoma resulted in significantly (p = 0.024) prolonged OS compared with FasL/CD95L-negative high-risk primary melanomas. In contrast, loss of FasL/CD95L expression in melanoma metastases resected before chemotherapy was associated with significantly prolonged median survival (p = 0.0139). Conclusion: Presence of FasL/CD95L expression in primary malignant melanoma and the loss of FasL/ CD95L expression in metastases seem to be positive prognostic factors.

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“…There are conflicting reports of the expression of FAS and FASligand (tumor suppressor proteins of the tumor necrosis family) in melanomas and nevi and neither has been shown to be an independent prognostic factor. [110][111][112] Flice inhibitory protein was studied by Bullani et al 113 and identified in 24 of 29 melanomas but only 1 of 32 benign nevi. Cancer/testis antigens are proteins normally expressed only in the testis but aberrantly expressed in many types of malignancies.…”

Section: Markers Of Tumor Cell Proliferationmentioning

confidence: 99%

Immunohistochemical characteristics of melanoma

et al. 2008

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Melanoma has a wide spectrum of histologic features which mimic epithelial, hematologic, mesenchymal, and neural tumors. Immunohistochemistry has been the primary tool to distinguish melanomas from these other tumors; it has also been studied for use as an adjunct to distinguish benign and malignant melanocytic tumors and to elucidate prognosis. Furthermore, there has been extensive effort to find a suitable marker to differentiate spindle cell and desmoplastic melanoma from other tumors. We have reviewed the literature investigating melanocytic differentiation markers, proliferation markers, immunomodulatory markers, signaling molecules, and nerve growth factors and receptors. Despite the proliferation of immunohistochemical markers, S‐100 remains the most sensitive marker for melanocytic lesions, while markers such as HMB‐45, MART‐1/Melan‐A, tyrosinase, and MITF demonstrate relatively good specificity but not as good sensitivity as S‐100. No marker has proven useful in distinguishing spindle cell and desmoplastic melanomas from other tumors. Ki67 remains the most useful adjunct in distinguishing benign from malignant melanocytic tumors. None of the markers reviewed has been shown conclusively to have prognostic value for melanocytic neoplasms.

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Expression of Fas and Fas ligand in uveal melanoma: biological implication and prognostic value

Cited by 25 publications

References 35 publications

Tumor Infiltrating Lymphocytes in Uveal Melanoma: A Link with Clinical Behavior?

Tumor Infiltrating Lymphocytes in Uveal Melanoma: A Link with Clinical Behavior?

Expression of Fas Ligand (CD95L) in Primary Malignant Melanoma and Melanoma Metastases is Associated with Overall Survival

Immunohistochemical characteristics of melanoma

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