UMLS:C0027627 - FACTA Search

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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant melanomas of the oral and sinonasal mucosa are rare tumors. Amelanotic variants can, on occasion, be difficult to recognize by routine light microscopy. Immunohistochemical studies may be needed for a final diagnosis. A number of new monoclonal antibodies to melanocytic differentiation antigens have been studied recently on primary cutaneous and metastatic melanoma. However, little is known about these antibodies for the diagnosis of mucosal melanomas. In this study the authors analyzed 79 oral and sinonasal mucosal melanomas of 65 patients. A total of 35 tumors originated from the oral mucosa (21 primary tumors, eight local recurrences, and six metastases) and 44 melanomas were from the sinonasal tract (27 primary tumors, nine local recurrences, and eight metastases). Immunohistochemical studies were performed on paraffin-embedded tissues, using the following antibodies: anti-S-100 protein, T311 (anti-tyrosinase), A103 (anti-Mart-1/Melan-A), D5 (antimicrophthalmia-associated transcription factor), and HMB-45 (anti-gp100). Of 35 oral mucosal tumors, 34 (97%) were positive with anti-S-100 protein, 33 (94%) with T311, 30 (85%) with A103, 26 (74%) with D5, and 25 (71%) with HMB-45. All five desmoplastic melanomas of the oral mucosa were positive for S-100 protein, four for tyrosinase, and one each for HMB-45 and A103. No desmoplastic melanoma was positive with D5. All 44 sinonasal melanomas were positive for tyrosinase and Mart-1/Melan-A (100%). Forty-three (98%) were positive with HMB-45, 42 (95%) with anti-S-100 protein, and 40 (91%) with D5. These results reveal that T311 is the most sensitive marker for sinonasal melanomas and closely approaches the sensitivity of anti-S-100 protein for oral mucosal melanomas. For desmoplastic mucosal tumors, anti-S-100 protein remains the most sensitive marker.
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PMID:Expression of melanocytic differentiation markers in malignant melanomas of the oral and sinonasal mucosa. 1139 56

Accurate diagnosis of micrometastases in sentinel lymph nodes of cutaneous melanoma is critical for proper clinical management. S-100 protein and HMB-45 are the traditional immunomarkers widely used for this purpose. However, the interpretation of micrometastases by these markers is difficult with significant reduction in the diagnostic accuracy. S-100 protein demonstrates immunoreactivity for other nonmelanoma cells and obscures nuclear details, which are crucial for the interpretation of single cell metastases. We compared the new melanoma markers, Melan-A (clone A103) and MART-1 (clone M2-7C10), with S-100 protein and HMB-45, by examining 77 formalin-fixed paraffin-embedded sections of sentinel lymph nodes from 13 cases of primary cutaneous melanoma. CD68 (PG-M1) and hematoxylin-eosin-stained sections were also studied. Four pathologists interpreted the staining pattern after concealing the identity of each immunomarker. Az values (area under receiver operating characteristic curve) with receiver operating characteristic curve were higher with Melan-A (0.9742) and MART-1 (0.9779) compared with S-100 protein (0.8034) and HMB-45 (0.8651), demonstrating a higher diagnostic accuracy with Melan-A and MART-1 with superior detection of melanoma micrometastases. Melan-A and MART-1 showed sharp cytoplasmic immunoreactivity, almost exclusively restricted to the melanoma cells. Therefore, Melan-A and MART-1 are recommended for the evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma as a routine alternative to S-100 protein and HMB-45.
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PMID:Evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma: higher diagnostic accuracy with Melan-A and MART-1 compared with S-100 protein and HMB-45. 1147 88

The use of tyrosinase-based polymerase chain reaction (PCR) tests for the detection of circulating tumour cells in the blood of melanoma patients has led to highly controversial results. We here report on the analysis of 120 blood samples from 76 stage I to IV melanoma patients using a new MART-1/Melan-A PCR system in conjunction with the tyrosinase-specific assay reported in the literature. While there were no positive results in localized disease (stages I and II), identification of specific PCR products in stage III melanoma patients was restricted to the MART-1/Melan-A tests, with positive results in 11% (two out of 19) of the blood specimens analysed. Stage IV melanoma patients presented with the highest incidence of detectable mRNA levels, with positive results for tyrosinase in 38% (12 out of 32) and for MART-1/Melan-A in 22% (seven out of 32). By delineating 64 follow-up specimens covering sampling periods of up to 33 weeks, stable mRNA expression profiles were identified in nearly 95%. Four patients, however, showed PCR changes towards positive MART-1/Melan-A expression that were linked to metastatic melanoma progression. Taken together, PCR tests for tyrosinase and MART-1/Melan-A seem to lack sufficient detection frequencies for the routine monitoring of melanoma disease. Regarding the link between MART-1/Melan-A seroconversion and the development of metastatic disease, further studies are needed to clarify the clinical value of this observation.
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PMID:MART-1/Melan-A and tyrosinase transcripts in peripheral blood of melanoma patients: PCR analyses and follow-up testing in relation to clinical stage and disease progression. 1159 94

We developed the techniques of lymphatic mapping and sentinel node (SN) biopsy to improve the management of patients with high-risk (thick and deep) primary melanoma. The SN is the first lymph node on the direct lymphatic drainage path from the primary tumor. This node is uniquely immune-modulated by the primary tumor and is the node most likely to contain the earliest stages of metastases. Accurate assessment of the SN requires careful evaluation of multiple sections removed from the areas of the node most likely to contain tumor. These sections are stained with hematoxylin and eosin and by immunohistochemistry with antibodies directed to tumor-associated markers (S-100, HMB-45, and Melan-A/MART-1) in the case of melanoma and to cytokeratins for breast cancer. Studies are in progress to determine whether molecular biology techniques will detect additional nodes that contain truly occult tumor deposits.
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PMID:Current practice and future directions in pathology and laboratory evaluation of the sentinel node. 1159 89

Nodal nevi represent a potential diagnostic pitfall in the analysis of lymph nodes. They may be confused with metastatic melanoma or carcinoma. Although several morphologic guidelines exist for the recognition of nodal nevi, on occasion immunohistochemical studies may be helpful for diagnosis, especially when melanocytes extend into the lymph node parenchyma. To learn more about the immunohistochemical profile of nodal nevi we examined 15 nodal nevi for the expression of S-100 protein, gp100 (HMB-45), Melan-A/MART-1 (A103), and tyrosinase (T311), and we studied the expression of Ki-67 (MIB-1) in nodal nevi and 40 melanoma metastases (35 lymph node and five cutaneous metastases). All nodal nevi were homogeneously immunoreactive for S-100 protein, tyrosinase, and Melan-A/MART-1. Two nodal nevi were focally positive for gp100. Fourteen of 15 nodal nevi were completely negative for Ki-67. One large cellular nodal nevus showed nuclear labeling in <0.2% of melanocytes. All metastases showed MIB-1 labeling. However, the percentage of labeled tumor cells varied widely, ranging from 2% to 80%. These results demonstrate that MIB-1 and HMB-45 are helpful reagents for the distinction of nodal nevi from melanoma. Immunohistochemistry for S-100 protein, Melan-A/MART-1, or tyrosinase facilitates the recognition of melanocytes but does not distinguish between nodal nevus and metastatic melanoma.
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PMID:Expression of melanocyte differentiation antigens and ki-67 in nodal nevi and comparison of ki-67 expression with metastatic melanoma. 1236 50

Activation of CTL-mediated antitumor immunity to self-epitopes expressed by neoplastic cells is thought to be prevented, at any stage of tumor progression, by tolerance mechanisms. In contrast, in 74 American Joint Committee on Cancer stages I-IV melanoma patients, we found that development of lymph node metastases is a key event triggering CD8(+) T-cell-mediated immunity to self-epitopes encoded by melanocyte differentiation antigens. This was shown by the increased peripheral precursor frequency to Melan-A/Mart-1, gp100, and tyrosinase epitopes in stage III and IV compared with stage I and II patients, and by accumulation of functional memory T cells directed to Melan-A/Mart-1(26-35) in tumor-invaded lymph nodes. However, in tumor-invaded lymph nodes of most patients, CD8(+) T cells directed to melanocyte differentiation antigens or to tumor-restricted antigens (MAGE-3 and NY-ESO-1 epitopes), showed a CCR7(+) CD45RA(+) CD27(+) CD28(+) perforin(-) "precursor" phenotype. Only in 7 of 23 cases antigen-specific CD8(+) T cells in invaded lymph nodes showed a predominant CCR7(-) CD45RA(-) CD27(+) CD28(-) perforin(+) "preterminally differentiated" phenotype. In the latter subset of patients, by immunohistochemistry in lymph node lesions, we found that CD8(+) T lymphocytes intermingling with the neoplastic tissue expressed a CCR7(-) CD45RO(+)/RA(-) phenotype, whereas CD4(+) lymphocytes did not infiltrate the tumor. Furthermore, perforin and granzyme B were expressed on a higher fraction of the CD8(+) cells surrounding the invading tumor compared with the lymphocytes infiltrating the neoplastic tissue. In addition, no evidence for tumor regression was found in such metastatic lesions, as documented by absence of neoplastic cell necrosis or apoptosis. These data indicate that neoplastic cells in the lymph nodes and/or increased tumor burden in metastatic disease activate CD8(+) T-cell-mediated antitumor immunity to self-epitopes. However, the paucity of terminally differentiated CD8(+) T cells at tumor site suggests that immunotherapy strategies may require not only the boosting of tumor immunity, but also effective means to promote CD8(+) T-cell differentiation in the neoplastic tissue.
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PMID:Lack of terminally differentiated tumor-specific CD8+ T cells at tumor site in spite of antitumor immunity to self-antigens in human metastatic melanoma. 1275 Feb 77

Preclinical studies have shown that low dose IL-12 can potentiate cytotoxic lymphocyte responses. Since previous trials have demonstrated significant toxicity from high dose recombinant human IL-12 (rhIL-12), we sought to determine an optimal biological dose for rhIL-12 at lower doses when combined with peptide antigens. Two studies were undertaken. The rhIL-12 was administered at doses of 0 (placebo), 10, 30 and 100 ng/kg, subcutaneously in one study and intravenously in the other. Apart from IL-12 dosing, the studies were identical. Subjects had evaluable stage III or IV melanoma which expressed Melan-A by RT-PCR or immunohistochemistry. Melan-A (26-35) (EAAGIGILTV) and influenza matrix (58-66) (GILGFVFTL) peptides were administered intradermally on weeks 1, 2, 3, 4 and 9. Twenty-eight subjects were enrolled, of whom 24 were evaluable for clinical and immunological responses. Therapy was well tolerated, the main adverse event being influenza-like symptoms. Immunological monitoring included the evaluation of cutaneous reactions and assays for antigen-specific T-cells. Clinical responses included a complete response in a subject with small volume subcutaneous disease, a partial response in a subject with hepatic metastases, and mixed responses in pulmonary, pleural and nodal disease. Biopsies of accessible tumors showed infiltration with CD4+ and CD8+ lymphocytes capable of lysing Melan-A peptide-pulsed targets in vitro. No clear dose-dependent effect of rhIL-12 could be determined. The rhIL-12 given either s.c. or i.v. was well tolerated at doses of 10-100 ng/kg. Clinical and immunological activity has been observed in this study where peptides were administered either with or without low dose rhIL-12.
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PMID:Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma. 1286 18

The technique of sentinel lymph node (SLN) dissection is a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. Reverse transcription-polymerase chain reaction (RT-PCR) is emerging as a highly sensitive technique to detect micrometastases in SLNs, but its specificity has been questioned. A prospective SLN study in melanoma patients was undertaken to compare in detail immunopathological versus molecular detection methods. Sentinel lymphadenectomy was performed on 57 patients, with a total of 71 SLNs analysed. SLNs were cut in slices, which were alternatively subjected to parallel multimarker analysis by microscopy (haematoxylin and eosin and immunohistochemistry for HMB-45, S100, tyrosinase and Melan-A/MART-1) and RT-PCR (for tyrosinase and Melan-A/MART-1). Metastases were detected by both methods in 23% of the SLNs (28% of the patients). The combined use of Melan-A/MART-1 and tyrosinase amplification increased the sensitivity of PCR detection of microscopically proven micrometastases. Of the 55 immunopathologically negative SLNs, 25 were found to be positive on RT-PCR. Notably, eight of these SLNs contained naevi, all of which were positive for tyrosinase and/or Melan-A/MART-1, as detected at both mRNA and protein level. The remaining 41% of the SLNs were negative on both immunohistochemistry and RT-PCR. Analysis of a series of adjacent non-SLNs by RT-PCR confirmed the concept of orderly progression of metastasis. Clinical follow-up showed disease recurrence in 12% of the RT-PCR-positive immunopathology-negative SLNs, indicating that even an extensive immunohistochemical analysis may underestimate the presence of micrometastases. However, molecular analyses, albeit more sensitive, need to be further improved in order to attain acceptable specificity before they can be applied diagnostically.
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PMID:Detection of micrometastases in sentinel lymph nodes from melanoma patients: direct comparison of multimarker molecular and immunopathological methods. 1451 93

We performed a phase I/II clinical trial in metastatic melanoma patients with an ultraviolet (UV)-inactivated nonreplicating recombinant vaccinia virus enabling the expression, from a single construct, of endoplasmic reticulum-targeted HLA-A0201-restricted Melan-A/MART-1(27-35), gp100(280-288), and tyrosinase(1-9) epitopes, together with CD80 and CD86 costimulatory proteins. Corresponding soluble peptides were used to boost responses and granulocyte-macrophage colony-stimulating factor was used as systemic adjuvant. Safety and immunogenicity, as monitored with in vitro-restimulated peripheral blood mononuclear cells by cytotoxic T lymphocyte precursor (CTLp) frequency analysis and tetramer staining, were specifically addressed. Of 20 patients entering the protocol, 2 had to withdraw because of rapidly progressing disease. Immune responses were evaluated in 18 patients (stage III, n = 5; stage IV, n = 13) and increases in specific CTLp frequencies were observed in 15. In 16 patients responsiveness against all 3 antigens could be analyzed: 7 (43%), including all stage III cases, showed evidence of induction of CTLs specific for the three epitopes, and 2 (12%) and 4 (25%), respectively, showed reactivity against two or one tumor-associated antigen. In three stage IV patients no specific CTL reactivity could be induced. Increases in CTLp frequency were detected mostly after viral vaccine injections. However, in a majority of patients final CTLp levels were comparable to initial levels. Tetramer characterization of Melan-A/MART-1(27-35)-specific CTLs during the protocol also suggested preferential expansion after recombinant virus administration. Vector-specific humoral responses, frequently undetectable in stage IV patients, did not appear to prevent tumor-associated antigen-specific CTL induction. Aside from a single occurrence of transient grade 3 leukopenia, no major clinical toxicity was reported. Seventeen of 18 patients completed the 3-month trial (one patient died before the last delayed-type hypersensitivity test). Three displayed regression of individual metastases, seven had stable disease, and progressive disease was observed in seven patients. This is the first report on the administration of a UV-inactivated recombinant vaccinia virus coexpressing five transgenes in cancer patients. The results described here, in terms of safety and immunogenicity, support the use of this reagent in active specific immunotherapy.
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PMID:Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients. 1457 12

A 54-year-old female presented with the cutaneous metastases of the breast carcinoma that produced combination of pigmented zosteriform eruption on the trunk and eroded plaque on the scalp, 13 years after radical mastectomy. Histologically, zosteriform lesions displayed prominent infiltration of the epidermis in nesting or linear pattern by neoplastic cells with focal formation of intraepidermal and subepidermal vesicles due to discohesion of tumor cells and dermal edema. Examination of scalp plaque revealed ulcerations and infiltration of the epidermis with scattered basal and suprabasal malignant cells in pagetoid fashion. Immunohistochemically, tumor cells were cytokeratin 7- and estrogen receptor-positive and cytokeratin 20 negative. HMB-45 and Melan-A-stained numerous dendritic melanocytes intermingled with intraepidermal and superficial dermal tumor cells in the trunk lesion, whereas on the scalp, only occasional melanocytes surrounding intraepidermal carcinomatous cells were identified. Our case described, to our knowledge, so far unreported combination of individually rare, clinical and histological patterns of cutaneous metastases from breast carcinoma in a single patient.
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PMID:Epidermotropic metastases from breast carcinoma showing different clinical and histopathological features on the trunk and on the scalp in a single patient. 1474 90

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