mart-1-antigen and Lung-Neoplasms

Perivascular Epithelioid Cell Tumors (PEComa) is an extraordinarily rare mesenchymal neoplasm especially the malignant type originating from the lung. To date, only 8 cases of malignant or malignant potential pulmonary PEComa had been documented. Firm diagnostic criteria for malignant pulmonary PEComa need urgently to be established.. We report a challenging case of malignant pulmonary PEComa combined with a primary adenocarcinoma in a 54-year-old man. The PEComa-like tumor showed strong Melan-A and weak transcription factor E3 (TFE3) protein expression but no TFE3 gene rearrangement. The carcinoma-like nodule was recognized as a poorly differentiated primary lung adenocarcinoma.. Our case report was the first case of malignant pulmonary PEComa synchronous with a primary adenocarcinoma and studied the dilemma of diagnosing benign versus malignant criteria for this uncommon tumor.

Topics: Adenocarcinoma of Lung; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Down-Regulation; Humans; Lung Neoplasms; Male; MART-1 Antigen; Middle Aged; Neoplasms, Multiple Primary; Perivascular Epithelioid Cell Neoplasms; Pulmonary Surgical Procedures; Tomography, X-Ray Computed; Treatment Outcome

Early testing of aerosolized sargramostim therapy demonstrated anecdotal clinical responses in patients with metastatic melanoma associated with emergence of systemic antitumor immunity. To improve the clinical and immunologic efficacy of therapy without compromising patient safety, we performed a further dose escalation trial in patients with metastatic melanoma.. We conducted a dose-escalation clinical trial of HLA-A2 patients with metastatic melanoma to the lung treated with aerosolized granulocyte macrophage colony stimulating factor (GM-CSF) (500-2000 microg/dose, with increments of 250 microg/dose/cohort) twice/d on days 1 to 7 and 15 to 21 every 28 days until progression or severe toxicity to find a dose where a majority of patients develop antitumor immunity. Five patients were treated per each dose level. Clinical, immune, and safety parameters were examined.. The study accrued 40 patients. Toxicity was acceptable. All doses levels were exhausted without identifying a dose of GM-CSF at which a majority of patients (> or =3 of 5) demonstrated significant up-regulation of antitumor immunity. Three of 16 patients who were tetramer positive for at least one melanoma antigen (eg, MART-1) pretreatment developed an immune response (IR) to different tumor antigens. Two of 9 patients who were tetramer negative to all melanoma antigens pretreatment developed an IR against gp100. The greatest changes in antitumor immunity occurred at the highest dose levels.. A dose of aerosolized GM-CSF capable of inducing antitumor immunity in the majority of patients was not reached. All tested doses were well tolerated. The greatest increase in antitumor T cell IRs was achieved at the highest doses of GM-CSF.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Aged, 80 and over; Antigens, Neoplasm; Dose-Response Relationship, Drug; Female; Granulocyte-Macrophage Colony-Stimulating Factor; HLA-A2 Antigen; Humans; Immunologic Factors; Immunophenotyping; Immunotherapy; Lung Neoplasms; Male; MART-1 Antigen; Maximum Tolerated Dose; Melanoma; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Recombinant Proteins; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Treatment Outcome

The purpose of this study was to assess whether cationic nanoliposomes could address tumor vaccines to dendritic cells in the lungs in vivo. Nanoliposomes were prepared using a cationic lipid, dimethylaminoethanecarbamoyl-cholesterol (DC-cholesterol) or dioleoyltrimethylammoniumpropane (DOTAP), and dipalmitoylphosphatidylcholine (DPPC), the most abundant phospholipid in lung surfactant. The liposomes presented a size below 175 nm and they effectively entrapped tumor antigens, an oligodeoxynucletotide containing CpG motifs (CpG) and the fluorescent dye calcein used as a tracer. Although the liposomes could permanently entrap a large fraction of the actives, they could not sustain their release in vitro. Liposomes made of DOTAP were safe to respiratory cells in vitro, while liposomes composed of DC-cholesterol were cytotoxic. DOTAP nanoliposomes were mainly taken up by alveolar macrophages following delivery to the lungs in mice. Few dendritic cells took up the liposomes, and interstitial macrophages did not take up liposomal calcein more than they took up soluble calcein. Stimulation of the innate immune system using liposomal CpG strongly enhanced uptake of calcein liposomes by all phagocytes in the lungs. Although a small percentage of dendritic cells took up the nanoliposomes, alveolar macrophages represented a major barrier to dendritic cell access in the lungs.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Adjuvants, Immunologic; Animals; Cancer Vaccines; Cell Line, Tumor; Cell Survival; Cholesterol; CpG Islands; Dendritic Cells; Drug Delivery Systems; Fatty Acids, Monounsaturated; Female; Fluoresceins; Fluorescent Dyes; gp100 Melanoma Antigen; Lipopeptides; Liposomes; Lung; Lung Neoplasms; Macrophages, Alveolar; MART-1 Antigen; Mice; Nanoparticles; Quaternary Ammonium Compounds; Tissue Distribution

Non-small cell lung cancer (NSCLC) and melanoma are frequent entities in routine diagnostics. Whereas the differential diagnosis is usually straight forward based on histomorphology, it can be challenging in poorly differentiated tumors as melanoma may mimic various histological patterns. Distinction of the two entities is of outmost importance as both are treated differently. HMB45 and MelanA are recommended immunohistological markers for melanoma in this scenario. SOX10 has been described as an additional marker for melanoma. However, comprehensive large-scale data about the expression of melanoma markers in NSCLC tumor tissue specimen are lacking so far.. Therefore, we analyzed the expression of these markers in 1085 NSCLC tumor tissue samples. Tissue microarrays of NSCLC cases were immunohistochemically stained for HMB45, MelanA, and SOX10. Positivity of a marker was defined as ≥1% positive tumor cells.. In 1027 NSCLC tumor tissue samples all melanoma as well as conventional immunohistochemical markers for NSCLC could be evaluated. HMB45, MelanA, and SOX10 were positive in 1 (< 1%), 0 (0%) and 5 (< 1%) cases. The HMB45 positive case showed co-expression of SOX10 and was classified as large cell carcinoma. Three out of five SOX10 positive cases were SqCC and one case was an adenosquamous carcinoma.. Expression of HMB45, MelanA and SOX10 is evident but exceedingly rare in NSCLC cases. Together with conventional immunomarkers a respective marker panel allows a clear-cut differential diagnosis even in poorly differentiated tumors.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Lung Neoplasms; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; SOXE Transcription Factors

A 52-year-old man has unresectable locally recurrent melanoma of the left foot (Fig 1) and pulmonary metastases. Nine months before this presentation, he underwent a wide local excision and sentinel node biopsy for an acral melanoma on his left heel. Pathology disclosed Breslow thickness of 4.8 mm, Clark level IV, and tumor ulceration with a mitotic rate of 37 mitoses/mm(2). Both sentinel nodes in the left groin were positive for melanoma cells, which expressed S100, HMB45, and melan A. At subsequent left inguinal dissection, seven more nodes showed no additional nodal metastases. Within 3 months of his original surgery, the patient developed a local recurrence in the foot, and over the subsequent 6 months, he underwent serial local excisions and topical diphencyprone treatment. A recent staging scan showed at least 20 foci of in-transit disease in the left lower leg and foot, as well as a solitary lung metastasis (12 mm). His Eastern Cooperative Oncology Group performance status is 1, with no significant comorbidities. High-resolution melt followed by sequencing of an in-transit metastasis showed there is no BRAF exon 15 mutation. However, Sanger sequencing of KIT exons 9, 11, 13, and 17, performed as screening for a clinical trial enrolling patients with metastatic acral and mucosal melanomas, showed an exon 13 K642E mutation.

Topics: Biomarkers, Tumor; gp100 Melanoma Antigen; Humans; Leg; Lung Neoplasms; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Mutation; Neoplasm Recurrence, Local; Prognosis; Proto-Oncogene Proteins c-kit; S100 Proteins; Skin Neoplasms

Although a large number of immunohistochemical markers have been proven to be valuable in the differential diagnosis between epithelioid mesotheliomas and metastatic carcinomas involving the serosal membrane, no single antibody has been found that is absolutely sensitive and/or specific in making this distinction. A recent study reported melan A positivity in all 12 of the epithelioid mesotheliomas stained with a melan A antibody (clone A103). To fully determine the practical value of this antibody for assisting in the differential diagnosis of mesotheliomas, we investigated the expression of melan A (A103) in 40 mesotheliomas (27 epithelioid, 6 sarcomatoid, and 7 biphasic), 10 lung adenocarcinomas, and 10 serous carcinomas of the ovary. None of the mesotheliomas, lung adenocarcinomas, or serous carcinomas of the ovary were melan A (A103) positive. Similar staining results were observed in the 20 mesotheliomas immunostained in another institution using the same antibody clone from a different commercial source. On the basis of these results, it is concluded that in contrast to the initial report, melan A (A103) is not expressed in mesotheliomas and therefore, immunostaining with this antibody has no utility in the diagnosis of mesothelioma. The possible cause of the discrepancies between the results obtained in the present investigation and those of the initial study is discussed.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Biomarkers, Tumor; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Gene Expression; Humans; Immunohistochemistry; Lung Neoplasms; MART-1 Antigen; Mesothelioma; Ovarian Neoplasms; Pleural Neoplasms; Retrospective Studies

We encountered a clear cell tumor of the lung (CCTL) that was located peripherally, adjacent to the visceral pleura. The tumor could be directly observed during surgery. We believe that this case report describing the surgical and related pathological findings is highly informative. A chest radiograph during routine examination of an asymptomatic 65-year-old woman being treated for hypertension and hyperlipidemia revealed a nodular shadow in the left lung field. Wedge resection was performed by video-assisted thoracic surgery. The in vivo color of the tumor was red, suddenly changing to white after the tumor was clamped. Pathology examination showed a uniform pattern consisting of large clear cells without cytologic atypia or increased mitotic activity. Immunohistochemistry revealed tumor cells positive for vimentin and melanocytic markers (HMB-45 and melan-A) and negative for epithelial membrane antigen and cytokeratin. With the absence of clinical findings in both kidneys, the tumor was diagnosed as a benign CCTL.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Incidental Findings; Lung Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins; Perivascular Epithelioid Cell Neoplasms; Thoracic Surgery, Video-Assisted; Tomography, X-Ray Computed; Treatment Outcome; Vimentin

Topics: Adrenal Gland Neoplasms; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Cisplatin; Dacarbazine; Fatal Outcome; Female; Humans; Interferon-beta; Iofetamine; Liver Neoplasms; Lung Neoplasms; MART-1 Antigen; Mastectomy, Modified Radical; Melanoma; Middle Aged; Neoplasm Staging; Nimustine; Nipples; Radiopharmaceuticals; S100 Proteins; Skin Neoplasms; Tamoxifen; Tomography, Emission-Computed, Single-Photon; Vincristine

PEComa is a rare tumour developing from perivascular epithelioid cells (PEC) and is characterised by positive immunoreactivity for HMB45. Since PEComas are tumours having both a spindle cell component and an epithelioid and giant cell component, as seen in many sarcomas, as well as having a wide distribution in various organs and soft tissue, we reviewed cases originally diagnosed as sarcomas of the soft tissue in our institution and screened them by immunostaining for HMB45.. Consecutive soft tissue sarcomas (31 tumours) retrieved from the Surgical Pathology file at our institution for a period of 3 years were submitted for immunostaining for HMB45. Cases with positive HMB45 immunostaining were submitted for further immunostaining for MART1, CD68, S100 protein, cytokeratin AE1/3, EMA, vimentin, MSA and CD117.. Of 31 sarcomas, three tumours in the group of 11 malignant fibrous histiocytomas (MFH) and unclassified sarcomas showed positive immunoreactivity for HMB45 and MART1 in 1-25% of tumour cells. The three tumours were located in the lower extremities and measured 8, 11 and 12 cm in diameter. Patient gender male:female was 2:1 and ages were 46, 56 and 60 years. Microscopically, the tumours were composed of a variable proportion of spindled cells, multinucleated cells and epithelioid cells disposed in diffuse sheets or nests. Mitotic figures and necrosis were frequent. The immunoreactivity was diffuse for CD68, focal for AE3 and EMA, negative or focal for MSA and CD117, and negative for S100 and AE1. All three patients developed lymph node or distant metastases and died of the disease within 1-2 years.. PEComa re-screened from the group of high grade sarcomas without definite differentiation range from pleomorphic to monomorphic cytohistopathological features. Immunostaining for HMB45 of unclassified sarcomas is useful for the classification of these tumours. They occur preferentially in the lower extremities and have a high malignant potential when associated with large size, tumoural necrosis and high mitotic activity.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Epithelioid Cells; Fatal Outcome; Female; Humans; Immunohistochemistry; Lung Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Sarcoma; Soft Tissue Neoplasms

In melanoma patients, CD8+ cytotoxic T cells have been found recognizing self-proteins of which the expression is restricted to the melanocytic lineage. These melanocyte differentiation antigens are expressed in normal melanocytes as well as in 80-100% of primary and metastatic melanoma. In this report, six HLA-A*0201-subtyped metastatic melanoma patients vaccinated with dendritic cells (DCs) pulsed with autologous tumor lysates and keyhole limpet hemocyanin (KLH) were screened for the presence of CD8+ T cells specific for three HLA-A*0201-binding peptides derived from the melanosomal antigens MART-1/Melan-A, gp100, and tyrosinase. For this purpose, nonstimulated as well as in vitro peptide-stimulated peripheral blood mononuclear cells (PBMCs) were tested for peptide-specific IFN-gamma release by enzyme-linked immunosorbent spot (ELISpot) assays. Furthermore, expression of the melanosomal antigens MART-1/Melan-A, gp100, and tyrosinase in tumor lesions was analyzed by immunohistochemistry before and after vaccination. We also used the ELISpot technique to investigate whether KLH-specific T cells were induced and whether these cells released type 1 (IFN-gamma) and/or type 2 (IL-13) cytokines. Our data show induction of CD8+ T cells specific for the melanosomal peptides MART-1/Melan-A(27-35) or tyrosinase(1-9), as well as IFN-gamma-releasing KLH-specific T cells, in two of six vaccinated melanoma patients, but do not support an association between the induction of these T cells and clinical responses.

Topics: Antigens, Neoplasm; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Dendritic Cells; gp100 Melanoma Antigen; Hemocyanins; HLA-A Antigens; HLA-A2 Antigen; Humans; Hypersensitivity, Delayed; Immunoenzyme Techniques; Interferon-gamma; Lung Neoplasms; MART-1 Antigen; Melanoma; Membrane Glycoproteins; Monophenol Monooxygenase; Neoplasm Proteins; Peptide Fragments; Skin Neoplasms; Vaccination

A 10-year-old male cross-breed dog was referred for investigation of oral malignant melanoma. Fine-needle aspirates were taken from the draining submandibular lymph node. The presence of metastatic melanoma cells was confirmed by cytological examination and reverse transcription polymerase chain reaction (RT-PCR) using primers for the melanoma-associated antigens: tyrosinase and mart-1/melan A. Cytokine expression in the lymph node was evaluated by multiplex RT-PCR, which demonstrated the presence of mRNA for IL-10 and TGF-beta1. However, IL-2, IL-4 and IFNgamma mRNA could not be detected, suggesting a lack of immune activation. Thoracic radiographs showed a lesion within the caudal lung fields suggestive of pulmonary metastasis. The dog developed signs of dyspnoea and collapse and was euthanased four days later. This case illustrates that molecular techniques can be used to aid clinical staging of canine oral malignant melanoma, and suggests that immunosuppressive cytokines could be involved in the pathogenesis of disease.

Topics: Animals; Antigens, Neoplasm; Biopsy, Needle; Cytokines; Diagnosis, Differential; DNA Primers; Dog Diseases; Dogs; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; MART-1 Antigen; Melanoma; Monophenol Monooxygenase; Mouth Diseases; Neoplasm Proteins; Radiography; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: Adrenal Gland Neoplasms; Antibodies, Neoplasm; Antibody Specificity; Antigens, Neoplasm; Biopsy, Needle; Bone Neoplasms; Humans; Liver Neoplasms; Lung Neoplasms; MART-1 Antigen; Melanoma; Neoplasm Metastasis; Neoplasm Proteins; Pancreatic Neoplasms

Evidence is growing for both humoral and cellular immune recognition of human tumor antigens. Antibodies with specificity for antigens initially recognized by cytotoxic T lymphocytes (CTLs), e.g., MAGE and tyrosinase, have been detected in melanoma patient sera, and CTLs with specificity for NY-ESO-1, a cancer-testis (CT) antigen initially identified by autologous antibody, have recently been identified. To establish a screening system for the humoral response to autoimmunogenic tumor antigens, an enzyme-linked immunosorbent assay (ELISA) was developed using recombinant NY-ESO-1, MAGE-1, MAGE-3, SSX2, Melan-A, and tyrosinase proteins. A survey of sera from 234 cancer patients showed antibodies to NY-ESO-1 in 19 patients, to MAGE-1 in 3, to MAGE-3 in 2, and to SSX2 in 1 patient. No reactivity to these antigens was found in sera from 70 normal individuals. The frequency of NY-ESO-1 antibody was 9.4% in melanoma patients and 12.5% in ovarian cancer patients. Comparison of tumor NY-ESO-1 phenotype and NY-ESO-1 antibody response in 62 stage IV melanoma patients showed that all patients with NY-ESO-1(+) antibody had NY-ESO-1(+) tumors, and no patients with NY-ESO-1(-) tumors had NY-ESO-1 antibody. As the proportion of melanomas expressing NY-ESO-1 is 20-40% and only patients with NY-ESO-1(+) tumors have antibody, this would suggest that a high percentage of patients with NY-ESO-1(+) tumors develop an antibody response to NY-ESO-1.

Topics: Antibodies, Neoplasm; Antigens, Neoplasm; Autoantibodies; Breast Neoplasms; Colonic Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lung Neoplasms; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Membrane Proteins; Monophenol Monooxygenase; Neoplasm Proteins; Neoplasms; Ovarian Neoplasms; Proteins; Recombinant Proteins; Repressor Proteins