Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The detection of early micrometastasis or disseminated single tumor cells poses a problem for conventional diagnosis procedures. Using a panel of monoclonal antibodies against cytokeratin and the 17-1A epithelial antigen we identified immunocytochemically tumor cells in bone marrow of patients with breast cancer (n = 155) and colorectal cancer (n = 57) at the time of surgery of the primary tumor. Monoclonal antibody CK2, recognizing the human cytokeratin component 18 in simple epithelia, appeared to be the most suitable reagent because of its negative reaction with bone marrow samples of the noncarcinoma patients (n = 75). Its specificity was further demonstrated in a double-marker staining procedure using an anti-leukocyte common antigen monoclonal antibody (T200) as counterstain. A comparative analysis showed that immunocytology was clearly superior to conventional cytology (n = 212) and histology (n = 39). In 9.5-20.5% of patients without distant metastasis, tumor cells could be detected in bone marrow. We found a significant correlation between tumor cells in bone marrow and conventional risk factors, such as distant metastasis or lymph node involvement. In a first approach toward immunotherapy we demonstrated in 3 patients that infused monoclonal antibody 17-1A can label single tumor cells in bone marrow in vivo. We then used this approach to follow up 7 patients undergoing 17-1A therapy in an adjuvant clinical trial.
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PMID:Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. 244 26

The emerging clinical relevance of bone marrow micrometastasis has prompted several investigations, using a variety of immunocytochemical approaches. The present study was designed to evaluate some of the variables affecting the immunocytochemical detection of individual epithelial tumor cells in bone marrow. Using an alkaline phosphatase-antialkaline phosphatase staining technique, we evaluated bone marrow aspirates from 358 patients with primary carcinomas of the breast (n = 150), lung (n = 66), prostate (n = 42), or colorectum (n = 100). Individual tumor cells in cytological preparations were detected with monoclonal antibody (MAb) CK2 to the epithelial cytokeratin component 18 (CK18), which has been validated in extensive clinical studies. In addition, the utility of the broad-spectrum MAb A45-B/B3 was explored in this study. The high specificity of MAbs CK2 and A45-B/B3 was supported by analysis of bone marrow from 75 noncarcinoma control patients and by double-marker analysis with MAbs to mesenchymal marker proteins (CD45 and vimentin). In contrast, MAbs E29 and HMFG1, directed to mucin-like epithelial membrane proteins, cross-reacted with hematopoietic cells in 26.7-42.7% of all samples tested. The majority of the 154 positive samples (43.0%) from cancer patients displayed less than 10 CK18-positive cells per 8 x 10(5) marrow cells analyzed. The detection rate, however, was affected by blood contamination of the aspirate, the number of aspirates analyzed, and the number of marrow cells screened per aspiration site. Comparative immunostaining of bone marrow specimens with MAbs CK2 and A45-B/B3 indicated that downregulation of CK18 in micrometastatic carcinoma cells occurs in about 50% of the 172 samples analyzed, regardless of the primary tumor origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. 753 Jan 32

We developed a sensitive technique of detecting circulating tumor cells in carcinoma patients, using CD45 immunomagnetic separation to isolate epithelial cells in blood samples and specific polymerase chain reaction analysis to identify point mutations of the K-ras gene. The method is based on the fact that the peripheral blood mononuclear cells (PBMC) that express CD45 antigen are trapped with anti-CD45 conjugated supramagnetic microbeads while the carcinoma cells that do not express CD45 antigen are not trapped and pass through the magnetic fields. This method concentrated the number of carcinoma cells 3.3 times. After this separation, the modified method of mutant allele specific amplification was applied and this method was able to ten control carcinoma cells in a background of 107 PBMC. A preliminary clinical study demonstrated that six cases of end-stage carcinoma with K-ras mutations in the primary tumor showed the same mutations in the peripheral blood samples, while two cases without K-ras mutation in the primary tumor and 10 healthy volunteers showed no mutation in the peripheral blood samples. The results suggest that this method may be very useful to detect circulating carcinoma cells in the patient whose primary tumor shows K-ras mutations.
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PMID:Detection of ras gene mutations in peripheral blood of carcinoma patients using CD45 immunomagnetic separation and nested mutant allele specific amplification. 959 95

A new method for detecting circulating tumor cells that is based on magnetic-activated cell separation (MACS) and nested mutant allele-specific amplification (nested MASA) was evaluated in patients with colorectal cancer using the p53 and K-ras genes as genetic markers. By negative selection with anti-CD45 monoclonal antibody-conjugated supermagnetic microbeads, the proportion of tumor cells was enriched 9-fold. By the combination of MACS and nested MASA, 10 tumor cells in 10(7) normal peripheral blood mononuclear cells could be detected without false-positives. Using this method, we examined blood taken from the tumor drainage veins of 23 patients with colorectal cancer. Eighty-seven percent (20/23) of primary tumor tissues showed p53 and/or K-ras gene mutations. Forty-five percent (9/20) of patients with p53 and/or K-ras mutations in the primary tumor showed the same mutated genes in the blood samples. There was a significant association between the presence of p53 and K-ras gene mutation in the blood and tumor size, depth of invasion, and venous invasion. Blood gene mutation was detected in 80% (4/5) of samples from patients with synchronous liver metastases. Sixty percent (3/5) of patients with mutant genes in the blood developed asynchronous liver metastases after surgery. The overall survival of patients with p53 and/or K-ras gene mutation-positive findings in blood was significantly shorter than that of patients testing negative on Kaplan-Meier analysis. Our results suggest that the method may be useful for reliable detection of tumor cells circulating in the blood and may help to identify patients at high risk for relapse.
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PMID:Detection of tumor cells in blood using CD45 magnetic cell separation followed by nested mutant allele-specific amplification of p53 and K-ras genes in patients with colorectal cancer. 1095 7

We describe 9 cases of precursor B-cell lymphoblastic lymphoma (LYL) without evidence of marrow or blood involvement. Four patients had superficial nodal disease, 2 cutaneous involvement, and 1 each ovarian, retroperitoneal, or tonsillar primary tumor. Six patients had limited disease; 3 patients were stage III. Immunophenotyping revealed a terminal deoxynucleotidyl transferase (TdT)-positive, immature B-cell population with variable expression of CD10, CD20, and CD45. All patients are in complete clinical remission (median follow-up, 14 months). A literature review yielded 105 patients with a diagnosis of precursor B-cell LYL based on less than 25% marrow involvement. Of these, 64% were younger than 18 years. Skin, lymph nodes, and bone were the most common sites of disease. Mediastinal involvement was uncommon. TdT, CD19, CD79a, CD10, and HLA-DR were the most frequently expressed antigens, while CD45 and CD20 were expressed in only two thirds of the cases. Cytogenetic analysis showed additional 21q material as a recurring karyotypic abnormality. At a median follow-up of 26 months, 74% of patients were alive; the median survival was 19 months for patients dying of disease. Comparison with precursor B-cell acute lymphoblastic leukemia showed several overlapping features, although distinct differences were identified.
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PMID:Precursor B-cell lymphoblastic lymphoma. A study of nine cases lacking blood and bone marrow involvement and review of the literature. 1139 84

A 63-year-old man was admitted to our hospital for complaints of a painless knot in his right testicle. The patient underwent orchiectomy for suspicion of malignancy. Pathologic examination detected a firm, circumscribed mass that consisted histologically of noncohesive, large, undifferentiated tumor cells diffusely infiltrating the testicular interstice. Because of the patient's advanced age and the structure of the neoplastic cells, the differential diagnosis favored a lymphoma over a malignant germ cell tumor but also included a dedifferentiated metastatic neoplasm. Immunohistochemistry was tailored accordingly and was completed using three successive panels of antibodies. Immunostaining with the first panel of antibodies directed against leukocyte epitopes (CD45, CD20, and CD3) remained negative and made a lymphoma unlikely. The subsequent panel (cytokeratin AE1/3, cytokeratin 18, and HMB-45) helped to rule out a malignant melanoma and aided to settle the diagnosis of a metastatic carcinoma. The reaction pattern of the last panel of antibodies pointed to a pulmonary origin of the putative primary tumor (PSA-negative, TTF-1-positive, and CK20-negative). The diagnosis of a metastasized poorly differentiated adenocarcinoma of the lung was confirmed by autopsy 5 months later. This case represents the extremely rare occurrence of a testicular metastasis as a primary manifestation of an occult neoplasm and shows the usefulness of an integrated site-specific clinicomorphologic approach that should precede and guide the choice of diagnostic immunoreagents.
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PMID:Immunohistochemical assessment of a testicular tumor in a 63-year-old patient: proposal for an integrated clinicopathologic approach. 1261 Mar 64

We describe the clinicopathologic findings in a so far unrecognized thymic tumor. The tumor occurred in a 70-year-old woman with respiratory distress but neither myasthenia gravis nor other symptoms. Metastases or another primary tumor were absent. The well-circumscribed neoplasm was located in the thymic region, measured 18 x 12 x 8 cm, and showed a homogeneous, tan-colored, soft cut surface. By histology, the tumor lacked a true capsule and a lobular growth pattern, was almost devoid of stroma, and infiltrated among remnant thymus lobules. The polygonal tumor cells formed solid sheets, trabeculae, or occurred as single cells that resembled hepatocytes. Proliferative activity was low. Portal structures, sinuses, and bile were absent as were areas of conventional thymoma, adenocarcinoma, or germ cell tumor. The tumor expressed cytokeratins 7 and 19, alpha1-antitrypsin, alpha1-antichymotrypsin, and hep-Par-1. Alpha-fetoprotein (AFP), human beta-chorionic gonadotropin (beta-HCG), placental alkaline phosphatase, CD5, CD30, CD31, CD34, CD45, CD68, CD99, S-100, HMB45, desmin, actin, or neuroendocrine markers were not expressed, and intratumorous CD1a+ or TdT+ immature T cells were absent. AFP was repeatedly undetectable in the blood. Mediastinal tumor recurrence was detected 6 months after surgery. Following radiochemotherapy, the patient has remained free of disease for 26 months. We conclude that this tumor is a thymic carcinoma (WHO type C thymoma). A diagnosis of hepatoid yolk sack tumor appears unlikely considering absence of a bona fide germ cell component, lack of AFP expression, and the patient's female gender. Because of its morphologic and immunohistochemical features, we propose the term "hepatoid thymic carcinoma" for this new type of thymic carcinoma.
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PMID:Hepatoid thymic carcinoma: report of a case. 1504 16

A 70-year-old Japanese man presented to our hospital with a 1-month history of progressive general fatigue and anorexia. A physical examination revealed severe anemic condition, mild persistent splenomegaly, and no palpable surface lymph nodes. He had pleural effusion and ascites, though no malignant cells were detected in the effusion. He eventually died without any diagnosis of his disease. Immunohistochemical staining of his tumor after autopsy showed atypical cells that were negative for epithelial membrane antigen (EMA), keratin (AE1/3), keratin-20, vimentin, factor VIII, leukocyte common antigen (LCA/T200; CD45), myeloperoxidase (MPO), terminal deoxynucleotidyl transferase (TdT), lysozyme, CD1a, CD3, CD4, CD10, CD15, CD20 (L26), CD21, CD23, CD34, CD43, CD56, CD68, CD79a, CD138, and EBER-1 in situ. Only a few scattered cells expressed CD30, but they showed no staining for anaplastic large-cell lymphoma kinase (ALK). A few scattered cells expressed S-100 antigen and the majority of cells dominantly expressed dendritic cell-associated antigens (CD35, FDC, Ki-M1p). In conclusion, we found this unknown primary tumor to be consistent with a follicular dendritic cell tumor with anaplastic features.
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PMID:Follicular dendritic cell tumor as an unknown primary tumor. 1738 Apr 43

Multiple myeloma is an incurable plasma cell malignancy for which existing animal models are limited. We have previously shown that the targeted expression of the transgenes c-Myc and Bcl-X(L) in murine plasma cells produces malignancy that displays features of human myeloma, such as localization of tumor cells to the bone marrow and lytic bone lesions. We have isolated and characterized in vitro cultures and adoptive transfers of tumors from Bcl-xl/Myc transgenic mice. Tumors have a plasmablastic morphology and variable expression of CD138, CD45, CD38, and CD19. Spectral karyotyping analysis of metaphase chromosomes from primary tumor cell cultures shows that the Bcl-xl/Myc tumors contain a variety of chromosomal abnormalities, including trisomies, translocations, and deletions. The most frequently aberrant chromosomes are 12 and 16. Three sites for recurring translocations were also identified on chromosomes 4D, 12F, and 16C. Gene expression profiling was used to identify differences in gene expression between tumor cells and normal plasma cells (NPC) and to cluster the tumors into two groups (tumor groups C and D), with distinct gene expression profiles. Four hundred and ninety-five genes were significantly different between both tumor groups and NPCs, whereas 124 genes were uniquely different from NPCs in tumor group C and 204 genes were uniquely different from NPCs in tumor group D. Similar to human myeloma, the cyclin D genes are differentially dysregulated in the mouse tumor groups. These data suggest the Bcl-xl/Myc tumors are similar to a subset of plasmablastic human myelomas and provide insight into the specific genes and pathways underlying the human disease.
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PMID:A transgenic mouse model of plasma cell malignancy shows phenotypic, cytogenetic, and gene expression heterogeneity similar to human multiple myeloma. 1748 17

Biomarkers of papillary thyroid carcinoma (PTC) metastasis can accurately identify metastatic cells and aggressive tumor behavior. To find new markers, serial analysis of gene expression (SAGE) was done on three samples from the same patient: normal thyroid tissue, primary PTC, and a PTC lymph node metastasis. This genomewide expression analysis identified 31 genes expressed in lymph node metastasis, but not in the primary tumor. Eleven genes were evaluated by quantitative real-time reverse transcription-PCR (qPCR) on independent sets of matched samples to find genes that were consistently different between the tumor and metastatic samples. LIMD2 and PTPRC (CD45) showed a statistically significant difference in expression between tumor and metastatic samples (P < 0.0045), and an additional gene (LTB) had borderline significance. PTPRC and LTB were tested by immunohistochemistry in an independent set of paired samples, with both markers showing a difference in protein expression. All 20 metastases from 6 patients showed expression in both markers, with little or no expression in primary tumor. Some of these markers could provide an improved means to detect metastatic PTC cells during initial staging of a newly diagnosed carcinoma and/or to rule out recurrence. The functional role of these genes may also provide insight into mechanisms of thyroid cancer metastasis.
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PMID:Molecular profiling of matched samples identifies biomarkers of papillary thyroid carcinoma lymph node metastasis. 1769 95


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