mart-1-antigen and Colonic-Neoplasms

Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with CP-675,206, a fully human anti-CTLA4 monoclonal antibody, may break peripheral immunologic tolerance leading to effective immune responses to cancer in humans. A phase I trial was conducted to test the safety of CP-675,206.. Thirty-nine patients with solid malignancies (melanoma, n = 34; renal cell, n = 4; colon, n = 1) received an intravenous (IV) infusion of CP-675,206 at seven dose levels. The primary objective was to determine the maximum-tolerated dose and the recommended phase II dose.. Dose-limiting toxicities and autoimmune phenomena included diarrhea, dermatitis, vitiligo, panhypopituitarism and hyperthyroidism. Two patients experienced complete responses (maintained for 34+ and 25+ months), and there were two partial responses (26+ and 25+ months) among 29 patients with measurable melanoma. There have been no relapses thus far after objective response to therapy. Four other patients had stable disease at end of study evaluation (16, 7, 7, and 4 months). Additionally, five patients had extended periods without disease progression (36+, 35+, 26+, 24+, and 23+ months) after local treatment of progressive metastases. Longer systemic exposure to CP-675,206 achieved in higher dose cohorts predicted for a higher probability of response.. CP-675,206 can be administered safely to humans as a single IV dose up to 15 mg/kg, resulting in breaking of peripheral immune tolerance to self-tissues and antitumor activity in melanoma.

Topics: Adult; Aged; Antibodies, Blocking; Antibodies, Monoclonal; Antibodies, Neoplasm; Antigens, CD; Antigens, Differentiation; Antigens, Neoplasm; Autoimmune Diseases; Cancer Vaccines; Colonic Neoplasms; CTLA-4 Antigen; Female; Humans; Immune Tolerance; Immunotherapy; Infusions, Intravenous; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma; Middle Aged; Neoplasm Proteins; Neoplasms; Regression Analysis; T-Lymphocyte Subsets; Treatment Outcome

Topics: Biomarkers, Tumor; Biopsy; Colectomy; Colonic Neoplasms; Colonic Polyps; Desmin; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; MART-1 Antigen; Middle Aged; Perivascular Epithelioid Cell Neoplasms

Malignant gastrointestinal melanoma is usually a metastatic lesion. We report the case of a 67-year-old female patient who presented with intermittent abdominal pain, fever, rigor and diarrhoea. CT scan of the abdomen revealed a large mass at the right iliac fossa with features concerning for intra-abdominal abscess. Exploratory laparotomy confirmed the preoperative diagnosis of abscess, and a right hemicolectomy was performed. Histopathological examination of the surgical specimen was indicative of malignant melanoma, and immunohistochemical examination showed positivity to S100 protein, Melan-A, HMB-45 and vimentin. A series of postoperative clinical, laboratory and imaging examinations revealed no suspicious lesions in the skin, eye, leptomeninges or other sites. Therefore, the diagnosis of primary colonic melanoma was confirmed. Only 36 additional cases of primary colonic melanoma have been reported to date. These rare neoplasms are challenging to diagnose and usually require a multidisciplinary treatment approach, including surgery, chemotherapy and possibly immunotherapy or radiotherapy.

Topics: Abdomen; Abdominal Pain; Aftercare; Aged; Biomarkers, Tumor; Chemotherapy, Adjuvant; Colectomy; Colon, Ascending; Colonic Neoplasms; Diarrhea; Female; gp100 Melanoma Antigen; Humans; Laparotomy; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Rare Diseases; S100 Proteins; Tomography, X-Ray Computed; Treatment Outcome; Vimentin

We present a case of perivascular epithelioid cell tumor (PEComa), which clinically and histologically mimics a gastrointestinal stromal tumor (GIST).. A 42-year-old woman was found to have a mass in the left flank during her annual medical checkup. Computed tomography examination revealed a submucosal tumor of the descending colon. Surgeons and radiologists suspected that the lesion was a GIST, and left hemicolectomy was performed without biopsy. Microscopic examination showed that the lesion was composed of spindle and epithelioid cells, which were immunohistochemically negative for c-kit and positive for platelet-derived growth factor receptor (PDGFR) α. Initial diagnosis of PDGFRα-positive GIST was made. However, gene analysis did not reveal mutations in PDGFRα. Additional immunohistochemistry showed that tumor cells were positive for human melanin black 45 (HMB45), melanA, and the myogenic marker calponin. A final diagnosis of PEComa was made.. PEComa should be included in the differential diagnosis of PDGFRα-positive spindle cell tumors in the wall of the gastrointestinal tract.

Topics: Adult; Biopsy; Calcium-Binding Proteins; Calponins; Colectomy; Colon, Descending; Colonic Neoplasms; Diagnosis, Differential; Female; Gastrointestinal Stromal Tumors; Humans; Immunohistochemistry; MART-1 Antigen; Microfilament Proteins; Mutation; Perivascular Epithelioid Cell Neoplasms; Positron-Emission Tomography; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Tomography, X-Ray Computed

Gastrointestinal involvement by malignant melanoma is predominantly a metastatic phenomenon. Although primary malignant melanoma of the gastrointestinal tract has been documented in the esophagus, stomach, small bowel, and anorectum, the incidence of primary melanoma of the colon is rare and remains controversial in most cases. We present a case of solitary malignant melanoma of the transverse colon occurring in a 64-year-old African American male patient. Complete dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or an ocular primary lesion. Microscopic examination of the resection specimen revealed malignant melanoma, which was confirmed by immunohistochemical positivity for S100 and melan-A. We believe that this tumor represents a primary colonic malignant melanoma.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Colonic Neoplasms; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanoma; Middle Aged; Neoplasm Proteins; S100 Proteins; Treatment Outcome

Topics: Antigens, Neoplasm; Colon; Colonic Neoplasms; Colonoscopy; Female; Humans; Ileal Diseases; Intussusception; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins

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

Tumor-infiltrating lymphocytes (TILs) were grown from four distinct anatomic sites from a patient with metastatic melanoma. The metastatic sites included a tumor-involved lymph node, a subcutaneous lesion obtained from the chest wall, a portion of bowel, and adrenal gland. TILs grown from each anatomic site over the course of 20 days in the presence of 6,000 IU/ml recombinant interleukin-2 exhibited comparable growth rates. Between days 30 and 45, the TILs were a mixture of CD3+ CD4+ and CD3+ CD8+ lymphocytes expressing the alpha beta form of the T-cell receptor. TILs derived from each anatomic site specifically lysed autologous tumor obtained from all four anatomic sites. In fine specificity analysis, the TILs exhibited human leukocyte antigen (HLA-A2)-restricted lysis of fresh tumor targets and cultured melanoma cell lines. Each TIL recognized a product of the MART-1 gene, and specifically, the monomer peptide MART-1(27-35). Thus lymphocytes reactive with the MART-1 melanoma antigen appeared to be widely distributed in diverse metastases in this patient. This information, along with previous data on the reactivity of multiple patients to this antigen, attests to its dominance in the immune reactivity of humans to melanoma.

Topics: Adrenal Gland Neoplasms; Antigens, Neoplasm; Axilla; Cell Division; Cell Line; Colonic Neoplasms; Cytotoxicity, Immunologic; Humans; Immunophenotyping; Lymph Nodes; Lymphocytes, Tumor-Infiltrating; MART-1 Antigen; Melanoma; Neoplasm Proteins; Thorax