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S Ferrone

Publications and source records attributed to S Ferrone.

At least 19 recordsLinked to original sources
PubMed2006

Regulation of high molecular weight-melanoma associated antigen (HMW-MAA) gene expression by promoter DNA methylation in human melanoma cells.

The human high molecular weight-melanoma associated antigen (HMW-MAA) is a membrane-bound chondroitin sulfate proteoglycan that is variably expressed in a high percentage of melanoma cell lines and tumors. Since the mechanism(s) regulating HMW-MAA expression has(ve) not been defined, in this study, we have examined whether promoter DNA methylation regulates the level of HMW-MAA expression. In melanoma cell lines, the level of HMW-MAA mRNA and protein expression is coordinately regulated, implicating a transcriptional control mechanism. Consistent with a role for regulation by DNA methylation, we have found that a dense CpG island flanks the human HMW-MAA gene transcriptional start site. Methylation-specific PCR and sodium bisulfite DNA sequencing analyses indicate that the HMW-MAA promoter is heavily methylated in melanoma cell lines, melanoma lesions and normal lymphocytes that do not express HMW-MAA; in contrast, the HMW-MAA promoter is not methylated in melanoma cell lines and tumors that express this antigen. In addition, HMW-MAA expression is markedly induced in HMW-MAA-negative melanoma cell lines by incubation with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. In summary, our results establish DNA methylation as a key regulator of HMW-MAA expression by human melanoma cells. This information represents a useful background to optimize immunotherapeutic strategies targeting HMW-MAA.

Antigens, Neoplasm↗
PubMed2005

Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival?

PURPOSE: To characterize HLA class I antigen expression in non-small cell lung cancer (NSCLC) lesions, and to assess the clinical significance of these molecules' downregulation. METHODS: One hundred and ninety primary formalin fixed, paraffin embedded NSCLC lesions were stained with HLA class I heavy chain-specific mAb HC-10. Results were scored as percentage of stained tumor cells and categorized into three groups: 0-24% (negative), 25-75% (heterogeneous) and >75% (positive). HLA class I antigen expression was correlated with clinical and pathologic predictors of time to progression and survival and analyzed using the chi-square test. Association between HLA class I antigen expression and survival was assessed using Cox regression models, while controlling for confounders. RESULTS: HLA class I antigen expression was negative, heterogeneous and positive in 153, 25 and 12 primary NSCLC lesions, respectively. Independent variables significantly associated with survival included tumor stage, PS and weight loss. The median survival times were 40.6, 44.0 and 17.9 months for patients with a HLA class I antigen expression scored as negative, heterogeneous and positive, respectively. CONCLUSION: HLA class I antigen defects were found with high frequency (93.6%) in NSCLC lesions. HLA class I antigen downregulation was associated with improved survival, although this association was not statistically significant. These results, which parallel similar findings in uveal melanoma and in breast carcinoma, raise the possibility that NK cells may play a role in the control of NSCLC tumors.

Adult↗
PubMed2005

Selective monomorphic and polymorphic HLA class I antigenic determinant loss in surgically removed melanoma lesions.

The analysis of human leukocyte antigen (HLA) class I allospecificity expression in malignant lesions has been hampered by the limited availability of HLA class I allospecificity-specific monoclonal antibodies (mAbs) which stain tissues in immunohistochemical (IHC) reactions. During the 12th International Histocompatibility Workshop, the HLA and cancer component made available a panel of mAbs capable of detecting monomorphic, locus- and allo-specific HLA class I antigenic determinants in surgically removed frozen tissue sections by IHC staining. In the present study, we have utilized this panel of mAbs to analyze the expression of HLA class I allospecificities in 33 primary and in 11 metastatic lesions surgically removed from HLA-typed patients with malignant melanoma, as this information contributes to determine the extent of HLA class I antigen abnormalities in melanoma lesions. HLA class I antigens were downregulated in six (18.2%) of the primary lesions and in six (54.5%) of the metastatic lesions. Selective loss of HLA-A and HLA-B antigens was detected in two (6.1%) and in one (3.0%), respectively, of the primary lesions, but in none of the metastases. HLA-A and HLA-B antigens were downregulated in three (9.1%) and four (36.4%) of the primary and metastatic lesions, respectively. Selective loss of one or more HLA class I allospecificities was found in 10 (33.0%) and two (18.0%) of the 33 primary and 11 metastatic melanoma lesions analyzed, respectively. HLA class I antigen abnormalities were present in 16 (48.5%) of the 33 primary lesions analyzed (i.e. six lesions demonstrating abnormal reactivity with HLA class I monomorphic-specific mAb, two lesions demonstrating selective abnormal reactivity with HLA-B locus-specific mAb, one lesion demonstrating selective abnormal reactivity with HLA-A and HLA-B locus-specific mAbs, and seven lesions demonstrating selective abnormal reactivity with HLA class I allele-specific mAb). Furthermore, HLA class I antigen abnormalities were present in nine (81.8%) of the 11 metastatic lesions analyzed (i.e. six lesions demonstrating abnormal reactivity with HLA class I monomorphic-specific mAb, one lesion demonstrating selective abnormal reactivity with HLA-A locus-specific mAb, and two lesions demonstrating selective abnormal reactivity with HLA class I allele-specific mAb). It cannot be ruled out that the frequency of HLA class I allospecificity abnormalities is higher, as the expression of several HLA class I allospecificities could not be investigated because of the lack of appropriate probes. The frequency of HLA class I antigen defects in primary lesions was significantly correlated with primary lesion thickness, an important prognostic marker in melanoma, arguing for a potential clinical significance of HLA class I antigen abnormalities in melanoma. In conclusion, the results of the present study (i) demonstrate that the frequency of HLA class I allospecificity abnormalities in primary melanoma lesions is markedly higher than that of total HLA class I antigen downregulation described in the literature; (ii) corroborate our previous findings that staining of melanoma lesions with mAb to monomorphic determinants of HLA class I antigens does not detect selective HLA class I allospecificity loss; and (iii) demonstrate for the first time selective loss of antigenic determinants expressed on HLA class I molecules in melanoma lesions. The latter finding indicates that at least two mAbs recognizing distinct antigenic determinants on the HLA molecule being investigated should be used for IHC staining of tissue sections in order to prove that lack of immunostaining reflects actual loss of the corresponding HLA molecule and not selective loss of antigenic determinants.

Adult↗
PubMed2005

Development and characterization of human constitutive proteasome and immunoproteasome subunit-specific monoclonal antibodies.

Delta (Y), MB1 (X), and Z are the three catalytic beta-subunits located in the inner rings of the constitutive proteasome, an intracellular multicatalytic complex responsible for the generation of peptides presented by human leukocyte antigen (HLA) class I antigens to T cells. When cells are incubated with interferon-gamma, delta (Y), MB1 (X), and Z are replaced by LMP2, LMP7, and LMP10, respectively, leading to the expression of immunoproteasome which generates peptides with increased affinity for HLA class I antigens. The characterization of the expression of constitutive proteasome and immunoproteasome subunits in cells, normal tissues, and malignant lesions has been hampered by the lack or limited availability of constitutive proteasome and immunoproteasome subunit-specific monoclonal antibodies (mAbs), which are suitable for immunohistochemical staining. To overcome this limitation, we generated human delta (Y), MB1 (X), Z, LMP2, LMP7, and LMP10-specific mAb-secreting hybridomas from BALB/c mice immunized with peptides and recombinant fusion proteins. The mAbs SY-5, SJJ-3, NB-1, SY-1, HB-2, and TO-7 were shown to be specific for delta (Y), MB1 (X), Z, LMP2, LMP7, and LMP10, respectively, as they react specifically with the corresponding molecules when tested with a human B lymphoid LG2 cell lysate in Western blotting and with the peptide derived from each molecule in enzyme-linked immunosorbent assay. The reactivity of the six mAbs with the corresponding intracellular antigens resulted in intracellular staining when the mAbs were tested with microwave-treated and saponin-permeabilized cells in indirect immunofluorescence and with formalin-fixed, paraffin-embedded tissue sections in immunohistochemical reactions. These results suggest that the constitutive proteasome and immunoproteasome subunit-specific mAbs we have developed are useful probes to characterize the expression of proteasome subunits in normal tissues and in pathological lesions.

Animals↗
PubMed2003

Specificity and functional characteristics of anti-HLA-A mAbs LGIII-147.4.1 and LGIII-220.6.2.

Only three anti-HLA-A monoclonal antibodies (mAbs) have been described in the literature. Two of them recognize determinants shared by only a few HLA-A allospecificities. The third one, mAb 3G11, recognizes a determinant shared by most HLA-A allospecificities. Being an IgM, the latter mAb is not likely to be a useful probe in immunohistochemical reactions and in functional assays. Therefore, in the present study we have characterized the specificity of the mAbs LGIII-147.4.1 and LGIII-220.6.2. The two mAbs that do not share idiotypic determinants recognize distinct but spatially close antigenic determinants expressed on most of the gene products of the HLA-A locus. Specifically, the determinant recognized by mAb LGIII-220.6.2 is expressed on HLA-A1, -A2, -A3, -A26, -A28, -A29, -A30, -A33, -A36, -A74 and -A80 allospecificities. The determinant recognized by mAb LGIII-147.4.1, which appears to be located on the amino-acid residues 79-83 of the heavy chain, is expressed on all HLA-A allospecificities but HLA-A23, -A24, -A25 and -A32. Because of its broad reactivity, the mAb LGIII-147.4.1 was characterized in a number of assays. It was found to be a useful probe to measure the HLA-A antigen level in serum, to assess the HLA-A restriction of cytotoxic T lymphocytes (CTL) and to monitor HLA-A antigen expression in normal and malignant lesions.

Animals↗
PubMed2003

Endoplasmic reticulum chaperone-specific monoclonal antibodies for flow cytometry and immunohistochemical staining.

Endoplasmic reticulum (ER) chaperones of the antigen processing machinery play a crucial role in HLA class I antigen complex assembly and antigen presentation. The characterization of the expression of these chaperones in normal tissues and malignant lesions has been hampered by the lack or limited availability of ER chaperone-specific monoclonal antibodies (mAb) that are suitable for immunohistochemical staining. To overcome this limitation, we have generated human calnexin, ERp57, calreticulin and tapasin-specific mAb-secreting hybridomas from BALB/c mice immunized with peptides and recombinant proteins. The mAb TO-5, TO-2, TO-11 and TO-3 were shown to be specific for calnexin, ERp57, calreticulin and tapasin, respectively, as they react specifically with the corresponding immunizing peptides in ELISA and with the corresponding proteins when tested with human lymphoid cell lysates in Western blotting. Furthermore, the reactivity of the four mAb with the corresponding intracellular antigens yielded intracellular staining when the mAb were tested with formalin-fixed, microwave-treated and saponin-permeabilized cells in indirect immunofluorescence and with formalin-fixed, paraffin-embedded tissue sections in the immunoperoxidase reaction. These results suggest that the ER chaperone-specific mAb we have developed are useful probes for characterizing the expression of ER chaperones of the antigen processing machinery in normal and pathological cells. This information will contribute to defining the effects of abnormalities in their expression on HLA class I antigen expression and function and on the interactions of target cells with the host's immune system.

Animals↗
PubMed2003

HLA-DR antigen-negative acute myeloid leukemia.

Human leukocyte antigen (HLA) Class II antigens are variably expressed on acute myeloid leukemia (AML) blasts. The biological and clinical significance of HLA Class II antigen expression by AML cells is not known. Therefore, we sought to characterize cases of AML without detectable HLA-DR expression. Samples from 248 consecutive adult AML patients were immunophenotyped by multiparameter flow cytometry at diagnosis. HLA-DR antigens were not detected on AML cells from 43 patients, including 20 with acute promyelocytic leukemia (APL), and 23 with other subtypes of AML. All APL cases had t(15;17), but there were no characteristic chromosome abnormalities in non-APL cases. No direct expression of other antigens was identified in HLA-DR-negative APL and non-APL cases. Interestingly, cells from three HLA-DR-negative non-APL patients had similar morphology to that of the hypogranular variant of APL. This morphology, however, was not present in any HLA-DR-positive AML cases. Treatment response was similar in the 23 HLA-DR-negative non-APL and the 205 HLA-DR-positive patients. Finally, relapse was infrequently associated with changes in HLA-DR antigen expression, as the HLA-DR antigen was lost at relapse in only 4% of HLA-DR-positive cases, and was gained at relapse in only 17% of HLA-DR-negative cases. We conclude that HLA-DR-negative AML includes approximately equal numbers of APL and non-APL cases, and that the morphology of HLA-DR-negative non-APL cases can mimic the hypogranular variant of APL. The diagnosis of APL cannot be based on morphology and lack of HLA-DR antigen expression; rather, it requires cytogenetic or molecular confirmation.

Acute Disease↗
PubMed2001

Immune escape of melanoma: first evidence of structural alterations in two distinct components of the MHC class I antigen processing pathway.

Sequence analyses of the transporter associated with antigen processing (TAP) in tumor cell lines with deficient MHC class I surface expression identified a bp deletion at position 1489 near the ATP-binding domain of Tap1, causing a frameshift in one melanoma cell line. The impaired TAP1 protein expression was associated with deficient TAP2 protein expression, peptide binding, translocation, and MHC class I surface expression. Stable TAP1 gene transfer reconstitutes the described defects, whereas lysis by HLA-A2-restricted CTLs was still abrogated. This was attributable to a 2-bp insertion at position 890 in the HLA-A2 gene and was corrected after HLA-A2 cotransfection. This study describes for the first time mutations in two distinct components of the MHC class I antigen processing pathway, suggesting an immune selection against CTLs recognizing both TAP-dependent and -independent T-cell epitopes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Soluble human leukocyte antigen--G serum level is elevated in melanoma patients and is further increased by interferon-alpha immunotherapy.

BACKGROUND: The nonclassic human major histocompatibility complex class I antigens human leukocyte antigen (HLA)--G are proposed to protect tumor cells from natural killer cell lysis. In the current study, the authors measured soluble HLA-G molecules (sHLA-G) in serum from patients with malignant melanoma. METHODS: Soluble HLA-G was determined in serum samples of 190 melanoma patients with various stages of disease, with or without current therapy including interferon (IFN)-alpha and different cytostatics in comparison to 126 healthy controls by using a two-step enzyme-linked immunoadsorbent assay. RESULTS: Serum sHLA-G was significantly (P < 0.0005) elevated in melanoma patients (mean +/- standard error of the mean [SEM] = 41.95 +/- 2.15 ng/mL) compared with healthy controls (mean +/- SEM = 22.92 +/- 1.51 ng/mL). Univariate analysis revealed a correlation of sHLA-G serum level with advanced stages of disease (P < 0.001) and tumor load (P < 0.05). Patients undergoing immunotherapy with IFN-alpha (n = 31) showed an increased serum sHLA-G (mean +/- SEM = 62.05 +/- 7.58 ng/mL; P < 0.0005), whereas other treatment regimens (n = 24) did not influence sHLA-G serum concentrations. Multivariate analysis revealed treatment with IFN-alpha as the only impact factor for elevated serum sHLA-G, lacking any correlation with stage of disease or tumor burden. Furthermore, IFN-alpha was found to upregulate HLA-G cell surface expression on circulating monocytes. sHLA-G serum level was not associated with recurrence free or overall survival. CONCLUSIONS: This study shows increased sHLA-G serum concentrations in melanoma patients and additional enhancement upon treatment with IFN-alpha. The level of serum sHLA-G, however, had no negative impact on patients' prognosis.

Antibodies, Monoclonal↗
PubMed2001

TAP1 down-regulation in primary melanoma lesions: an independent marker of poor prognosis.

Melanoma tumor thickness is a major prognostic factor. Thin lesions, however, may metastasize, and sometimes thick tumors may not. To investigate the role of HLA class I-mediated antigen presentation, we correlated the expression of components of the antigen-processing machinery in primary melanoma lesions with their thickness and with the development of metastases. Seventeen formalin-fixed, paraffin-embedded primary melanomas thinner than 0.76 mm and 21 thicker than 1.50 mm were stained with anti-LMP2, -LMP7, -TAP1, -TAP2, -HLA class I and -beta2-microglobulin monoclonal antibodies. Twenty patients remained tumor-free in the follow-up period (10.5 +/- 1.8 years). Eighteen patients relapsed within a median period of 15.0 months following tumor excision. Expression of all markers in the tested lesions was down-regulated, the frequency ranging from about 40% for LMP and TAP subunits to about 70% for HLA class I antigens. Expression of all markers was not correlated with tumor thickness. Only TAP1 and TAP2 down-regulation was significantly (p = 0.026 and 0.042, respectively) correlated with the development of metastases. This correlation was independent of tumor thickness for TAP1. We suggest that TAP1 and probably TAP2 expression in primary lesions represents an independent prognostic marker in melanoma. Abnormalities in antigen presentation may account for the lack of absolute correlation between tumor thickness and prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Active specific immunotherapy of malignant melanoma and peptide mimics of the human high-molecular-weight melanoma-associated antigen.

The realization that tumor cells utilize multiple mechanisms to escape from immune recognition and destruction has stimulated interest in developing and applying immunotherapeutic strategies which target both humoral and cellular immunity to malignant cells. As a result, the tumor-associated antigens (TAA) used as targets have to be expressed on the cell surface membrane of malignant cells. Furthermore, since most of the TAA used for active specific immunotherapy are self-antigens, a challenge facing tumor immunologists is to develop strategies which are effective in breaking tolerance to self-antigens. This chapter describes one strategy which relies on the use of peptide mimics of the human high-molecular-weight melanoma-associated antigen (HMW-MAA) as immunogens to implement active specific immunotherapy in patients with malignant melanoma. These mimics, which are isolated from phage display peptide libraries by panning with anti-HMW-MAA monoclonal antibodies, are expected to induce both humoral and cellular anti-HMW-MAA immunity.

Animals↗
PubMed2001

HLA class I antigen cell surface expression is preserved on acute myeloid leukemia blasts at diagnosis and at relapse.

Human leukocyte antigens (HLA) class I molecules restrict the interaction between cytotoxic T cells and target cells. Abnormalities in HLA class I antigen expression and/or function may provide tumor cells with a mechanism for escaping immune surveillance and resisting T cell-based immunotherapies. The potential for applying T cell-based immunotherapy in the treatment of acute myeloid leukemia (AML) has stimulated interest in analyzing HLA class I antigen expression on leukemic blasts in this disease. Little information is available in the literature. We have analyzed HLA class I antigen expression on bone marrow samples from 25 newly diagnosed AML patients by indirect immunofluorescence staining with monoclonal antibodies. Five of these patients were also studied at relapse. Leukemic blasts were resolved from normal lymphocytes by staining with antiCD45 antibody; CD45 expression is dim on leukemia cells, but bright on lymphocytes. HLA class I antigen expression was higher on leukemic blasts than on autologous lymphocytes in all but one case. Moreover, there was no significant change in HLA class I antigen expression at relapse. These results suggest that abnormalities in HLA class I antigens are infrequent in AML and should not represent a major obstacle to the application of T cell-based immunotherapies in this disease.

Acute Disease↗
PubMed2001

Association of HLA class I and class II antigen expression and mortality in uveal melanoma.

PURPOSE: Malignant transformation of cells is frequently associated with abnormalities in human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLA antigens mediate interactions of tumor cells with T cells and NK cells. Uveal melanoma is a highly malignant tumor of the eye and is characterized by a hematogenic spread to the liver. Little is known about the role of HLA expression in progression of this malignant disease. METHODS: In the present study HLA class I antigen, beta(2)-microglobulin (beta(2)-m), and HLA class II antigen expression was analyzed in primary uveal melanoma lesions by immunoperoxidase staining with monoclonal antibodies of 65 archival clinical samples. The results were correlated with the clinical course of the disease. RESULTS: HLA class I antigen expression and beta(2)-m expression were downregulated in 40 and 35 lesions, respectively. HLA class II antigens were expressed in 30 lesions. Patients with high HLA class I, including beta(2)-m, and HLA class II antigen expression in their primary melanoma lesions had a significantly decreased survival (P = 0.009, P < 0.001, and P = 0.006, respectively). CONCLUSIONS: The findings argue against a major role of cytotoxic T-lymphocyte (CTL)-mediated control of tumor growth in the clinical course of uveal melanoma and are compatible with a potential role of NK-cell-mediated control of hematogenic metastatic spread.

Adult↗
PubMed2000

Structural relatedness of distinct determinants recognized by monoclonal antibody TP25.99 on beta 2-microglobulin-associated and beta 2-microglobulin-free HLA class I heavy chains.

The association of HLA class I heavy chains with beta2-microglobulin (beta2m) changes their antigenic profile. As a result, Abs react with either beta2m-free or beta2m-associated HLA class I heavy chains. An exception to this rule is the mAb TP25.99, which reacts with both beta2m-associated and beta2m-free HLA class I heavy chains. The reactivity with beta2m-associated HLA class I heavy chains is mediated by a conformational determinant expressed on all HLA-A, -B, and -C Ags. This determinant has been mapped to amino acid residues 194-198 in the alpha3 domain. The reactivity with beta2m-free HLA class I heavy chains is mediated by a linear determinant expressed on all HLA-B Ags except the HLA-B73 allospecificity and on <50% of HLA-A allospecificities. The latter determinant has been mapped to amino acid residues 239-242, 245, and 246 in the alpha3 domain. The conformational and the linear determinants share several structural features, but have no homology in their amino acid sequence. mAb TP25.99 represents the first example of a mAb recognizing two distinct and spatially distant determinants on a protein. The structural homology of a linear and a conformational determinant on an antigenic entity provides a molecular mechanism for the sharing of specificity by B and TCRs.

Amino Acid Sequence↗
PubMed2000

Analysis by NMR spectroscopy of the structural homology between the linear and the cyclic peptide recognized by anti-human leukocyte antigen class I monoclonal antibody TP25.99*.

The anti-human leukocyte antigen (HLA) class I monoclonal antibody (mAb) TP25.99 has a unique specificity since it recognizes both a conformational and a linear determinant expressed on the beta(2)-mu-associated and beta(2)-mu-free HLA class I heavy chains, respectively. Previously, we reported the identification of a cyclic and a linear peptide that inhibits mAb TP25.99 binding to the beta(2)-mu-associated and beta(2)-mu-free HLA class I heavy chains (S. A. Desai, X. Wang, E. J. Noronha, Q. Zhou, V. Rebmann, H. Grosse-Wilde, F. J. Moy, R. Powers, and S. Ferrone, submitted for publication). The linear X(19) and cyclic LX-8 peptides contain sequence homologous to residues 239-242, 245, and 246 and to residues 194-198, respectively, of HLA class I heavy chain alpha(3) domain. Analysis by two-dimensional transfer nuclear Overhauser effect spectroscopy of the induced solution structures of the linear X(19) and cyclic LX-8 peptides in the presence of mAb TP25.99 showed that the two peptides adopt a similar structural motif despite the lack of sequence homology. The backbone fold is suggestive of a short helical segment followed by a tight turn, reminiscent of the determinant loop region (residues 194-198) on beta(2)-mu-associated HLA class I heavy chains. The structural similarity between the linear X(19) and cyclic LX-8 peptides and the lack of sequence homology suggests that mAb TP25.99 predominantly recognizes a structural motif instead of a consensus sequence.

Amino Acid Sequence↗
PubMed2000

Differential clinical significance of alpha(v)Beta(3) expression in primary lesions of acral lentiginous melanoma and of other melanoma histotypes.

Despite its potential clinical relevance, alpha(v)beta(3) expression has been analyzed only in a limited number of melanoma lesions, mostly nodular melanoma (NM) and superficial spreading melanoma (SSM). Therefore, in the present study, we have correlated alpha(v)beta(3) expression in 33 acral lentiginous melanomas (ALMs), 6 lentigo maligna melanomas, 7 mucosal melanomas, 12 NMs and 9 SSMs with their antigenic profile, with their histo-pathological characteristics and with the clinical course of the disease. Furthermore, we have compared alpha(v)beta(3) expression in ALM lesions with that in NM and SSM lesions since this information helps to clarify the relationship of the latter 2 histotypes with ALM. Such a relationship is uncertain since ALM has a clinical course similar to that of NM and SSM despite different antigenic profiles and biological characteristics. The level of alpha(v)beta(3) expression in primary lesions was not correlated with that of high-m. w. melanoma-associated antigen and intercellular adhesion molecule-1, with lesion thickness and with disease recurrence in ALM but was significantly correlated with these 4 parameters in the other melanoma histotypes analyzed. Therefore, alpha(v)beta(3) expression appears to have a differential clinical significance in ALM and in the other histotypes of melanoma we have analyzed since it appears to play a significant role in the progression of the disease only in non-ALM histotypes.

Adult↗