mart-1-antigen and Liver-Neoplasms

Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA).

Topics: Actins; Antibodies, Viral; Female; gp100 Melanoma Antigen; Hepatitis C, Chronic; Humans; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Microscopy, Fluorescence; Perivascular Epithelioid Cell Neoplasms; Tomography, X-Ray Computed; Ultrasonography

To improve the clinical diagnosis and recognition of hepatic epithelioid angiomyolipoma (HEAML).. Four cases of primary HEAML were confirmed based on the pathology archive system in our hospital from January 2009 to November 2015. The general state, clinical symptoms, imaging manifestations, histological results and immunohistochemistry of these patients were retrospectively reviewed and analyzed. Studies of HEAML published in the last 15 years were collected from PubMed and MEDLINE to summarize the clinical symptoms, imaging characteristics, pathological features and management of HEAML.. Four cases of primary HEAML were retrieved from our archives. These included three female patients and one male patient, with a mean age of 41.8 ± 11.5 years (ranging from 31 to 56 years). The mean tumor size was 7.3 ± 5.5 cm (ranging from 3.0 to 15 cm). In the contrast-enhanced imaging, the tumor was obviously enhanced in the arterial phase, but enhanced continuously or exhibited a slow-density masse during the venous and delayed phases. Histologically, the tumors mainly consisted of epithelioid cells that comprised approximately 95% of the total neoplastic mass. Although no metastases occurred in our patients, pathological studies revealed necrosis, mitotic figures and liver invasion in two patients, which indicates aggressive behavior. Immunohistochemical staining revealed that human melanoma black 45 (HMB-45) and Melan-A were positive in 4 cases. We only identified 81 cases with primary HEAML, including our present patients, from 26 articles available from PubMed and MEDLINE. The majority of the papers were published as case reports. Only 5 (5/75, 6%) cases were associated with tuberous sclerosis complex (TSC). More than half (35/66) were discovered incidentally upon physical examination. Approximately 65% (22/34) of the patients were misdiagnosed with HCC or other tumors before surgery. Approximately 10% (8/81) of the patients with HEAML had recurrence or metastasis after surgery, which was a very high and alarming rate.. HEAML is a very rare primary hepatic tumor that is often misdiagnosed before surgery. Patients should be followed closely after surgery because of its malignant potential.

Topics: Adult; Aged; Angiolipoma; Biomarkers, Tumor; Biopsy; Diagnostic Errors; Disease Progression; Epithelioid Cells; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Liver Neoplasms; Magnetic Resonance Imaging; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Predictive Value of Tests; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Tumor Burden

Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide-45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.

Topics: Angiomyolipoma; Antigens, Neoplasm; Female; Humans; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins; S100 Proteins

Topics: Humans; Liver Neoplasms; MART-1 Antigen; Melanins; Melanoma; Retrospective Studies

Topics: Biomarkers, Tumor; Chemoembolization, Therapeutic; Diagnosis, Differential; gp100 Melanoma Antigen; Hepatectomy; Humans; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Perivascular Epithelioid Cell Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

It is well known to pathologists that melanoma is "the great mimicker," looking like almost any other tumor, and able to metastasize anywhere in the body. We report a case of a 48-year-old female with a history of metastatic melanoma 4 years before, who presented with a hepatic mass. Microscopic examination of the liver mass revealed sheets of pleomorphic, epithelioid cells, which expressed a pan-melanocytic cocktail (MART1, HMB45, and tyrosinase). These findings were initially interpreted as metastatic melanoma and the case was transferred for dermatopathology consultation. We compared the morphology of this tumor to the primary melanoma and noticed that the primary melanoma showed nevoid cytology, morphologically distinct from the liver lesion. Consequently, we performed additional immunohistochemical studies, which determined that the liver mass was negative for S100 and SOX10, and established a final diagnosis of epithelioid angiomyolipoma. The key for reaching the correct diagnosis was the morphologic comparison with the original lesion and the evaluation of a wider immunohistochemical profile. For appropriate management in patients with new lesions, even in the context of a patient with known metastatic disease, it is essential to consider other neoplasms in the differential diagnosis.

Topics: Angiomyolipoma; Diagnosis, Differential; Epithelioid Cells; Female; gp100 Melanoma Antigen; Humans; Liver Neoplasms; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Monophenol Monooxygenase; Skin Neoplasms

Hepatic angiomyolipoma (HAML) is a rare and difficult-to-diagnose liver tumour. The aim of this study was to summarize experiences in the management of HAML and to recommend a practical treatment strategy.. We retrospectively studied 92 patients who were diagnosed with HAML and analysed the clinical presentation, histopathological features and treatment of the tumours encountered at our institute from May 2009 to June 2016.. The patients included 67 females and 25 males who underwent at least one radiographic examination. Sixty-eight patients underwent radical hepatectomy, two patients underwent liver biopsy, and 22 patients were treated with radiofrequency ablation after liver biopsy. The tumour cells correspondingly expressed both melanoma cell markers (HMB45, MART-1) and smooth muscle cell markers. Two patients were found to have tumour recurrence (2/92, 2.2%) after radical hepatectomy, and none of the patients died.. Diagnosis of HAML depends on pathological findings. The treatment strategy for HAML should be selected according to the tumour size, liver biopsy, location and clinical symptoms of HAML. Patients should be followed closely after surgery because of the malignant potential of HAML.

Topics: Adult; Aged; Angiomyolipoma; Biopsy; China; Female; gp100 Melanoma Antigen; Hepatectomy; Humans; Liver; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Recurrence, Local; Radiofrequency Ablation; Retrospective Studies

Epithelioid angiomyolipoma (EAML) of liver is a rare neoplasm. Hepatic EAML is often misdiagnosed as other neoplasms such as hepatocellular carcinoma due to non-specific clinical and radiologic features. The morphologic features under microscope and immunohistochemistry staining profile are important in the diagnosis EAML. Here, we report a case of 52-year-old man who found 1.2 cm mass in liver by routine checkup. On the impression of hepatocellular carcinoma, lateral sectionectomy of the liver was done. Microscopically, the tumor is composed of predominant epithelioid cells with vascular component and foamy cells. These cells were positive for HMB45, MelanA, and smooth muscle actin and negative for epithelial membrane antigen. The final diagnosis was hepatic EAML.

Topics: Angiomyolipoma; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Liver; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microscopy, Fluorescence; Middle Aged; Tomography, X-Ray Computed

Topics: Aged; Histocytochemistry; Humans; Immunohistochemistry; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Male; MART-1 Antigen; Melanoma; Microscopy; Radiography; Uveal Neoplasms

Topics: Adult; Angiomyolipoma; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Kidney Neoplasms; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasms, Multiple Primary; Tomography, X-Ray Computed; Tuberous Sclerosis; Young Adult

To study the clinicopathologic features, immunophenotype, histological diagnosis and prognosis of hepatic epithelioid angiomyolipoma.. Clinical data of 25 cases of hepatic epithelioid angiomyolipoma were collected along with follow-up study of the patients. The pathological features were documented and immunohistochemical study of various markers was performed with an emphasis on diagnosis and differential diagnosis.. Hepatic epithelioid angiomyolipoma was more commonly found in young women without characteristic clinical symptoms. Its morphological features were characterized by marked cytological atypia, relatively rare mitotic figures; radial distribution of tumor cells around the thin-walled blood vessels or muscular vessels; and the presence of common multinucleated giant cells and large ganglion-like tumor cells. The tumor cells expressed both melanoma cell markers (HMB45, MART-1) and smooth muscle cell markers (SMA). Tumor cells expressed various other markers including ER 16% (4/25), PR 32% (8/25), TFE3 24% (6/25) and p53 60% (15/25).. Hepatic epithelioid angiomyolipoma has variable morphological features and characteristic immunohistochemical phenotype. The differential diagnoses include a variety of tumors. The biological behavior of the tumor tends to be benign.

Topics: Age Factors; Angiomyolipoma; Biomarkers, Tumor; Diagnosis, Differential; Female; Follow-Up Studies; Gastrointestinal Neoplasms; Giant Cells; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Immunophenotyping; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Muscle, Smooth; Prognosis

To study the clinicopathologic features, immunophenotype and genetic changes of perivascular epithelioid cell neoplasms (PEComa).. A total of 25 cases of PEComa located in various anatomic sites were selected for immunohistochemical staining (SP or EnVision method). TFE3 fluorescence in-situ hybridization was also performed to determine the TFE3 gene status.. The age of patient ranged from 21 to 61 years (mean = 43 years). The male-to-female ratio was 1: 1.3. Histologically, 22 cases represented conventional angiomyolipomas, composed of a mixture of adipose tissue, spindle element, epithelioid smooth muscle cells and abnormal thick-walled blood vessels in various proportions. Three cases involving lung, soft tissue and broad ligament had subtle but distinctive morphologic features. Nested or sheet-like architecture with epithelioid or spindle cells was observed. Immunohistochemical study showed that HMB 45, melan A, smooth muscle actin and cathepsin K were expressed in 80% (20/25), 88% (22/25), 88% (22/25) and 100% (25/25) of PEComa, respectively. Within positive cases, the average proportion of positive tumor cells was 36%, 41%, 35% and 90% respectively for HMB 45, melan A, smooth muscle actin and cathepsin K. TFE3 was negative in all of the 22 renal and hepatic PEComa studied, while it was positive in the 3 cases of extra-hepatorenal PEComa. None of the 25 cases exhibited evidence of TFE3 gene fusion or amplification.. Extra-hepatorenal PEComa have distinctive morphologic features and are associated with TFE3 overexpression. Cathepsin K immunostaining demonstrates high sensitivity and specificity in PEComa, better than other commonly employed immunomarkers. This marker is thus useful in diagnosis of PEComa and distinction with other neoplasms.

Topics: Actins; Adult; Angiomyolipoma; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cathepsin K; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Perivascular Epithelioid Cell Neoplasms; Young Adult

Epithelioid angiomyolipomas (AMLs) of the liver are rare tumors with imaging and cytologic features overlapping with those of hepatocellular carcinomas. We report the fine needle aspiration and core biopsy findings of an epithelioid AML in the right hepatic lobe of a 32-year-old female with tuberous sclerosis. She had undergone renal transplantation 8 years previously after bilateral nephrectomy for renal AMLs and a 3-cm chromophobe renal cell carcinoma. Hepatocellular carcinoma was suspected during the initial cytologic and histologic examination based on the presence of numerous large polygonal cells with ample finely vacuolated or granular cytoplasm, low nucleocytoplasmic ratio, and mild nuclear pleomorphism in the smears, as well as a distinctive trabecular histologic pattern in the core biopsies. Immunoperoxidase stains showed that the neoplastic cells were negative for cytokeratins and positive for HMB45, Melan-A, and smooth muscle actin, establishing the diagnosis of epithelioid AML. To determine the distinguishing cytomorphologic features between epithelioid AML and HCC, we have compared the cytologic features of 15 cases of hepatic AML reported in the literature, including the present case, to the FNA cytologic findings of 38 consecutive cases of HCC diagnosed at out institution.

Topics: Adult; Angiomyolipoma; Biopsy, Fine-Needle; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Cell Nucleus; Cell Nucleus Shape; Cytoplasm; Diagnosis, Differential; Epithelioid Cells; Female; gp100 Melanoma Antigen; Humans; Kidney Transplantation; Liver; Liver Neoplasms; Magnetic Resonance Imaging; MART-1 Antigen; Melanoma-Specific Antigens; Nephrectomy

Angiomyolipoma (AML) is a rare mesenchymal neoplasm of the tumor, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle and adipose cells. Hepatic AML may demonstrate a marked histological diversity. We herein present one case of hepatic AML exhibiting prominent inflammatory cells in the background, which happened in a 61-year-old Chinese female patient, without signs of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background, including small lymphocytes, plasma cells, and eosnophils. The tumor cells were spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and arranged along the vessels or scattered among the inflammatory background. Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues. The tumor cells were positive immunostaining for HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor and deserves wider recognition for its occurrence as a primary hepatic tumor. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1828633072762370.

Topics: Actins; Angiomyolipoma; Biomarkers, Tumor; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Hepatectomy; Humans; Immunohistochemistry; Inflammation; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Predictive Value of Tests; Treatment Outcome

Uveal melanoma primarily metastasizes hematogenously with metastases often confined to the liver. The aim of this study was to investigate the presence of circulating tumor cells (CTC) in patients with metastatic disease as a marker for systemic disease and to determine their prognostic relevance.. Blood samples from 68 patients were collected at the time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as a surrogate marker for the presence of CTC was analyzed by real-time RT-PCR and compared with patient characteristics.. CTC were detected in 63% of all patients and in 67% of the 48 patients with only liver metastases. Univariate and multivariate analyses revealed PCR results and serum lactate dehydrogenase as independent prognostic factors for progression-free (hazard ratios 2.2/3.5) and overall survival (hazard ratios 4.0/6.5). Combination of PCR and lactate dehydrogenase divided the patient cohort into 3 groups with distinct prognosis.. CTC as evidence for systemic disease can be found in the majority of patients with metastatic uveal melanoma, including patients with visible disease confined to the liver. Detection of CTC-specific mRNA transcripts for tyrosinase and MelanA/MART1 by PCR is a poor prognostic factor for progression-free and overall survival. Characterization of CTC could improve the understanding of their biology.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Karnofsky Performance Status; L-Lactate Dehydrogenase; Liver Neoplasms; Male; MART-1 Antigen; Melanoma; Middle Aged; Monophenol Monooxygenase; Neoplastic Cells, Circulating; Proportional Hazards Models; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Rate; Uveal Neoplasms

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

Melanoma markers, especially the new microphthalmia transcription factor (mitf), have not been previously compared in hepatic and renal angiomyolipomas.. To evaluate expression of the novel melanocytic markers mitf and tyrosinase in angiomyolipomas, and to compare these markers with the established markers HMB-45 and melan-A in both hepatic and renal tumors.. Clinical, histopathologic, and immunohistochemical features of 15 hepatic angiomyolipomas were compared with those of 10 renal angiomyolipomas.. No significant differences between patients with hepatic angiomyolipomas and renal angiomyolipomas were found with respect to age, gender, race, and tumor size. Hepatic angiomyolipomas exhibited a predominance of the epithelioid smooth muscle cell component, in contrast to their renal counterparts, which were predominantly spindled. The smooth muscle cells expressed HMB-45 in 100% of cases in both groups, melan-A in 14 of 15 hepatic angiomyolipomas and 8 of 9 renal angiomyolipomas, mitf in 5 of 12 hepatic angiomyolipomas versus 6 of 10 renal angiomyolipomas, and tyrosinase in 3 of 12 and 2 of 10 hepatic angiomyolipomas and renal angiomyolipomas, respectively. The extent and intensity of immunostaining with HMB-45 and melan-A were dependent on whether spindled or epithelioid cells predominated; the epithelioid cells showed stronger and more widespread reactivity than the spindled cells.. We believe that the best immunohistochemical marker for confirming the diagnosis of angiomyolipoma is HMB-45, followed by melan-A. Routine use of mitf and/or tyrosinase is not indicated.

Topics: Adult; Aged; Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microphthalmia-Associated Transcription Factor; Middle Aged; Monophenol Monooxygenase; Neoplasm Proteins; Transcription Factors

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

To study the clinicopathologic features of hepatic angiomyolipoma (AML) and to investigate the feasibility of a new antibody-A103 as a diagnostic aid for AML.. Ten cases of AML were retrieved from hospital records and analyzed morphologically. Immunohistochemistry was performed on paraffin-embedded tissues with a panel of antibodies, including antibody-A103.. There were eight women and two men, with ages ranging from 38-58 years (median 45.7). Clinically, nine cases were asymptomatic and found by imaging techniques. None of the patients had associated tuberous sclerosis. All tumors were sharply demarcated from the surrounding liver parenchyma. Histologically they were composed of a heterogeneous mixture of three components: thick-walled blood vessels, spindle or epithelioid smooth muscle cells and adipose tissue. All tumors showed a strong immunoreactivity to A103, HMB-45 and smooth muscle actins. Follow-up information on all 10 cases showed a benign course with no signs of recurrence.. Hepatic AML is a rare mesenchymal tumor of the liver. A103 is a promising marker for a pathologic diagnosis of hepatic AML.

Topics: Actins; Adult; Angiomyolipoma; Antigens, Neoplasm; Desmin; Female; Humans; Immunohistochemistry; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Muscle, Smooth; Neoplasm Proteins; Platelet Endothelial Cell Adhesion Molecule-1; S100 Proteins; Vimentin

HMB-45-positive clear-cell epithelioid tumor arising in the ligamentum teres hepatis of a 13-year-old Japanese girl is described. The well-defined tumor was completely removed and measured 9 x 7 x 6 cm. Cut sections showed a tan-white, homogeneous appearances with no hemorrhage or necrosis. The tumor was composed of nests or sheets of polygonal or oval-shaped cells rich in clear or finely granular cytoplasm. Capillary network was well developed, and sinusoid vessels were often seen with occasional perivascular hyalinization. There was moderate nuclear atypia but mitotic figures were absent. Periodic acid-Schiff stain showed a large amount of glycogen digested by diastase. Immunohistochemical stains for smooth muscle actin, Melan-A, and HMB-45 were positive in most of the tumor cells. Stains for vimentin, muscle actin, and HAM56 were focally positive, whereas stains for desmin, cytokeratin, epithelial membrane antigen, S-100, CD34, CD68, CD99, neurofilament proteins, and estrogen/progesterone receptors were negative. Ultrastructurally, the cytoplasm contained a considerable number of mitochondria, monoparticipate or membrane-bound glycogen, and longitudinally oriented thin filaments with focal condensations and subplasmalemmal densities. The histopathology of the present case, originally interpreted as epithelioid leiomyoma, was consistent with clear cell "sugar" tumors. The present case may indicate ubiquitous distribution of clear cell "sugar tumors" of which histogenesis remains unknown but is presumed to be of perivascular epithelioid cell origin.

Topics: Actins; Adenocarcinoma, Clear Cell; Adolescent; Antigens, Neoplasm; Epithelioid Cells; Female; Humans; Immunohistochemistry; Ligaments; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Microscopy, Electron; Neoplasm Proteins

Angiomyolipomas are tumours of uncertain histogenesis, most often occurring in association with the kidney. A characteristic finding is their reactivity with HMB-45, a monoclonal antibody to the melanocyte-associated antigen gp-100. We tested 18 angiomyolipomas for their reactivity with A103, a monoclonal antibody to Melan-A (MART-1), another melanocyte-associated marker, and compared it with HMB-45. All cases were positive with both antibodies, yet most cases showed a more homogeneous staining pattern with A103. Normal kidney was immunohistochemically negative for both antibodies. We also performed RT-PCR assays for gp-100 and Melan-A in 4 of the 18 angiomyolipoma samples and in three normal kidney samples. All 4 angiomyolipoma specimens revealed mRNA for both melanocyte differentiation markers. gp-100 mRNA was found in the samples of normal kidney, but Melan-A mRNA was not. Our study shows that angiomyolipomas express the melanocyte-associated antigens Melan-A and gp-100 at the protein and at the mRNA level, suggesting a true expression of these antigens rather than cross-reacting epitopes. Based on the mRNA expression pattern, immunohistochemical analysis is the preferred method for the detection of gp-100, while Melan-A can be used at the protein and mRNA levels. Our study demonstrates that A103 is a useful marker for the diagnosis of angiomyolipomas.

Topics: Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; MART-1 Antigen; Melanocytes; Membrane Glycoproteins; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; Staining and Labeling

Distinguishing adrenal cortical neoplasms from either hepatocellular carcinomas or renal tumors can be difficult. Two recently described antibodies, A103 and inhibin A, are most often reported to be reactive with adrenal cortical neoplasms but with neither hepatocellular carcinoma nor renal cell carcinoma. To compare the sensitivity and specificity of these two antibodies in the diagnosis of adrenal cortical tumors, we stained 22 adrenal cortical adenomas, 4 adrenal cortical carcinomas, 25 hepatocellular carcinomas, and 43 renal tumors, including 33 renal cell carcinomas and 8 oncocytomas, with the A103 and inhibin A using an avidin-biotin complex technique. Fifteen (68%) of 22 adrenal adenomas and 2 (50%) of 4 adrenal cortical carcinomas were reactive with A103. Nineteen (86%) of 22 adrenal adenomas and 3 (75%) of 4 adrenal cortical carcinomas were reactive for inhibin A. None of the renal tumors or hepatocellular carcinomas reacted with A103, but 1 (4%) of 25 hepatocellular carcinomas (a high-grade pleomorphic tumor) and 1 (2%) of 43 renal tumors (a clear-cell renal cell carcinoma) were reactive with inhibin A. The cytoplasmic reactivity for A103 in adrenal tumors was coarsely granular and most common in clear-cell areas. Reactivity for inhibin was either cytoplasmic or membranous and stained both clear-cell and granular areas. We conclude that both antibodies are useful in the immunohistochemical diagnosis of adrenal cortical neoplasms and that A103 is slightly more specific and inhibin slightly more sensitive.

Topics: Adenoma; Adenoma, Oxyphilic; Adrenal Cortex Neoplasms; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Inhibins; Kidney Neoplasms; Liver Neoplasms; Male; MART-1 Antigen; Neoplasm Proteins; Sensitivity and Specificity

Peptides derived from melanocyte differentiation antigens have been identified as targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human melanoma Regression of antigen-expressing tumors as well as selection of antigen-loss variants in the presence of antigen-specific CTLs have previously been reported. In the present study, we determined the expression of the melanocyte differentiation antigens Melan A/MART-1 and tyrosinase by mRNA analysis and by immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311. Co-expression of Melan A/MART-1 and tyrosinase was detected by both methods in 18/20 melanomas tested. However, immunohistochemistry provided additional information on intensity and microheterogeneity of antigen expression that cannot be detected by mRNA analysis as a molecular basis for the escape from CTL recognition of antigen-negative tumor cells. Comparative analysis of repeated biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of Melan A/MART-1 expression in 4/5 and of tyrosinase in 2/5 samples in association with tumor progression. However, 3 of these patients had growing antigen-positive tumors in the presence of antigen-specific CTLs. This led us to assess the expression of MHC class I, the essential restriction element for CTL recognition, and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that strategies enhancing the expression of MHC class I and tumor-associated antigens need to be considered in attempts at making vaccination more effective.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biopsy; DNA Primers; Female; Genes, MHC Class I; HLA-A2 Antigen; Humans; Immunohistochemistry; Liver Neoplasms; Lymphatic Metastasis; Male; MART-1 Antigen; Melanoma; Middle Aged; Monophenol Monooxygenase; Neoplasm Proteins; Polymerase Chain Reaction; RNA, Messenger; Skin Neoplasms