Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An astoundingly high frequency of micrometastatic cells have been found in bone marrow aspirates of patients with colon carcinomas (G. Schlimok et al., J. Clin. Oncol., 8:831-837, 1990), although these tumors very rarely metastasize to the skeleton. This observation has raised questions about the malignant potential of such cells. In a first attempt to characterize this potential, we have assessed the expression of major histocompatibility complex (MHC) class I antigens on bone marrow micrometastases, inasmuch as down-regulation of these molecules is a potential mechanism to escape from MHC class I-restricted lysis by cytotoxic T-cells. The two groups of cancer patients compared were those with tumors known to rarely (stomach and colon cancer) or frequently (breast cancer) manifest skeleton metastases. Bone marrow aspirates taken from these patients were probed for individual disseminated tumor cells using the immunoalkaline phosphatase technique with monoclonal antibody CK2 to the epithelial differentiation antigen cytokeratin 18 (CK-18), as described previously (G. Schlimok et al., Proc. Natl. Acad. Sci. USA, 84:8672-8676, 1987). Specimens containing CK18-positive cells were colabeled with monoclonal antibody W6/32 directed to a framework (or nonpolymorphic) antigenic determinant of MHC class I heavy chains associated with beta 2-microglobulin. W6/32-positive CK-18-positive cells could be detected in 25 of 54 patients (46.3%) with significantly higher incidences in 26 breast cancer patients (61.9%) as compared to 28 patients with carcinomas of the stomach and colon (27.3 and 29.4%). Independent from the origin of the primary carcinoma, the incidence of W6/32-negative CK18-positive cells was positively correlated to both the differentiation grade of the primary tumor (P less than 0.05) and appeared to be linked to the occurrence of regional lymph node metastases (statistically not significant) determined by conventional histological examination. The present results demonstrate for the first time that down-regulation of MHC expression on individual micrometastatic cells correlates to the differential pattern of metastasis obtained by comparing breast and gastrointestinal carcinomas. This finding together with the suggestive link to clinical risk factors supports the significance of reduced MHC class I expression for the survival of residual metastatic cells which is a major determinant of prognosis for patients with solid tumors.
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PMID:Frequent down-regulation of major histocompatibility class I antigen expression on individual micrometastatic carcinoma cells. 187 15

With indirect immunofluorescence microscopy it is possible to visualize intermediate-sized filaments which show a cell-specific distribution and in this manner establish a light-microscopical diagnosis in certain cases which are difficult or impossible to differentiate using conventional methods. We applied the same method to tumours of the head and neck region. Intermediate-sized filaments were studied in four malignant lymphomas, seven carcinomas and four metastases of carcinomas. Malignant lymphomas showed a positive reaction with antibodies to vimentin, carcinomas a positive reaction with antibodies to keratin. Using a monoclonal antibody against a single keratin polypeptide (cytokeratin 18) a further subdivision of the carcinomas was possible. The keratinizing squamous cell carcinoma and two non-keratinizing squamous cell carcinomas showed a positive reaction with the conventional antibody against keratin, but a negative reaction with the monoclonal antibody against cytokeratin 18. One adenocarcinoma, two anaplastic carcinomas and one lymphoepithelial carcinoma were positive with the conventional antibody against keratin and with the monoclonal antibody against cytokeratin 18. Thus lymphoepithelial carcinomas and anaplastic carcinomas should probably not be regarded as special variants of squamous cell carcinoma. In all metastases the same intermediate-sized filaments were demonstrable as in the primary tumour. Certain advantages of immunofluorescence microscopy when compared to diagnostic electron microscopy are discussed.
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PMID:[Differential diagnosis of tumors of the head and neck using immunohistologic and electron optic studies]. 620 50

Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the identification of disseminated individual epithelial tumour cells in mesenchymal organs such as bone marrow. We have used a monoclonal antibody (mAB) against cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+ cells were detected in a sensitivity of 1 per 8 x 10(5) marrow cells using the alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We were able to detect CK18+ tumour cells in the marrow of 33% of patients with stage N0M0 prostate cancers. The incidence of CK18+ cells showed a significant correlation with established risk factors, such as local tumour extent, distant metastases and tumour differentiation. For further characterization of such cells in patients with prostate cancer, we developed an immunocytochemical procedure for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate-specific antigen (PSA). In a first step, cells were incubated with a murine mAb against PSA, followed by gold-conjugated goat anti-mouse antibodies. In a second step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hyperplasia (BPH).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical detection and phenotypic characterization of micrometastatic tumour cells in bone marrow of patients with prostate cancer. 752 Oct 88

The prerequisite for a curative resection of metastases is their restriction to the key organs, the liver and lungs, in the sense of a limited dissemination. For long-term prognosis, the type of primary tumor as well as the radical resection of lung and liver metastases is essential. To improve the process of surgical indication and therapy of tumors, clear definitions for the terms "tumor recurrence" and "metastases" have been agreed upon. Research and clinical investigation have led to a better understanding of tumor-regulating factors, some of which are briefly described: Metastasis promoting factors include the lack of E-cadherin, which leads to a local penetration of basal membranes by tumor cells; CD44 seems to play an important role in cell-cell and cell-matrix interactions, apparently increasing the metastatic potential of tumors and reducing the long-term survival of patients. High levels of urokinase in primary tumors are also associated with a poorer prognosis, as well as plasminogen inactivator inhibitor PAI II, which plays a crucial role in tumor growth. Positive findings in bone marrow aspirates of patients with different malignancies, stained for cytokeratin 18, either are associated with higher recurrence rates in colon and breast cancer or can be correlated to the prognosis of patients with gastric cancer. Technical aspects of surgery for hepatic, pulmonary and skeletal metastases are presented and discussed with respect to curative and palliative indications.
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PMID:Surgical treatment of tumor metastases: general considerations and results. 753 64

Serum levels of tissue polypeptide specific antigen (TPS), a cytokeratin 18 marker, and CA 15-3 were determined in 42 patients with metastatic breast cancer during routine treatment follow-up. At the time of proved metastatic disease, 86% of the values for TPS were above the upper reference value as compared to 93% for CA 15-3. The combined use of TPS and CA 15-3 increased the overall sensitivity. The levels of the tumor markers followed the course of disease during a follow-up period of 6-10 months, even though the dynamics of the changes of tumor markers levels differed in some patients. An increase in the tumor marker level of 25% or more was seen in 60% (TPS) and 52% (CA 15-3), respectively of the studied patients. TPS appeared to indicate changes faster than CA 15-3. The overall results of this study suggest the combined use of TPS and CA 15-3 in the monitoring of breast cancer patients is preferable.
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PMID:Determination of serum tumor markers TPS and CA 15-3 during monitoring of treatment in metastatic breast cancer patients. 869 38

Cytokeratins are polypeptides which constitute a subclass of intermediate filaments in epithelial cells. The serum tumour marker M3/M21 is based on monoclonal antibodies against the epitopes M3 and M21 of cytokeratin 18. In the present study, we measured M3/M21 serum levels in 50 patients with FIGO stage IB-IIB cervical cancer and in 50 control subjects using a two-site radiometric immunoassay directed against soluble fragments of cytokeratin 18. Median serum levels of M3/M21 in patients with cervical cancer and in normal controls were 70.6 U/ml (range 0-397.7) and 6.5 U/ml (range 0-205.2), respectively (Mann-Whitney U-test, P = 0.0001). Median serum levels of M3/M21 prior to therapy and 4 weeks after therapy were 104.2 U/ml (range 24.6-397.7) and 39.3 U/ml (range 0-234.7), respectively (Mann-Whitney U-test, P = 0.004). We found a significant correlation between elevated M3/M21 serum levels and metastatic disease in pelvic lymph nodes (Mann-Whitney U-test, P = 0.002). 24 patients relapsed after complete remission. In these patients, elevated M3/M21 serum levels before the detection of relapse by computed tomography was observed in 13 cases. Considering these preliminary results, further studies with an increased number of patients are justified to clarify the prognostic value and the monitoring abilities of M3/M21 in cervical cancer patients.
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PMID:Serum M3/M21 in cervical cancer patients. 929 24

Clear-cell odontogenic carcinoma (CCOC) is a rare neoplasm with malignant potential and unknown cytogenetic alterations. We describe the case of a 43-year-old woman who presented with an unusual odontogenic epithelial tumor. Histologically, the tumor was composed of clear-cell areas and exhibited a squamous pattern with little nuclear pleomorphism similar to benign squamous odontogenic tumor. Multiple small pulmonary nodules occurring 3 years after primary surgical treatment histologically closely resembled benign minute pulmonary meningothelial-like nodules (MPMN) with clear-cell features. Comparative genomic hybridization (CGH) and immunohistochemistry, performed as diagnostic adjuncts, revealed in the odontogenic tumor and the pulmonary lesions a very similar pattern of chromosomal aberrations (loss of 9, gains of 14q, 19 and 20 in both, and additional loss of 6 in the odontogenic tumor) and the same pattern of expression (positive for cytokeratin 5, 6, 8, 19 and negative for cytokeratin 18, epithelial membrane antigen, and vimentin), differing from that of MPMN. These findings confirmed the final diagnosis of metastasizing CCOC with partial squamous differentiation, substantiated the unfavorable prognosis of the clear-cell component, and highlighted the diagnostic impact of CGH and immunohistochemistry for classification of these morphologically peculiar pulmonary CCOC metastases.
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PMID:Clear-cell odontogenic carcinoma with pulmonary metastases resembling pulmonary meningothelial-like nodules. 1135 79

We investigated the distribution and fate of apoptotic bodies during human development and in the adult, using an antibody (M30) that recognizes a neo-epitope formed early in the apoptotic cascade by caspase cleavage of cytokeratin 18. In the fetus, we found extensive accumulation of M30-positive, non-phagocytosed fragments in the red pulp of the spleen, subcutaneous and submucosal vessels, the interstitium of the lung, and the glomerular mesangium of the kidneys. In the liver, M30-immunoreactive fragments were found inside macrophages in the sinusoids. The number of these fragments and the intensity of the immunostaining increased with the gestational age of the fetus. In the adult, M30-positive fragments were barely detectable in normal tissues. However, many pathological situations, including both chronic degenerative processes and metastatic cancer, were associated with accumulation of M30-positive fragments in the red pulp of the spleen. In the liver and kidney, no fragments could be detected. Remarkably, 13 of the 16 patients with metastasized cancer showed pronounced accumulation of M30-positive fragments containing hematoxylin-reactive material in the red pulp of the spleen. In the non-cancerous cases, such DNA-containing fragments were only seen in 9 of 94 cases. The results show that when apoptotic activity is high, as during development in the fetus or during metastasis and other pathological processes in the adult, the phagocytic clearance of apoptotic bodies can be overloaded. These apoptotic fragments then accumulate in the spleen. The visual detection of apoptotic fragments is concluded to reflect increased cell turnover.
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PMID:An immunohistochemical study of the clearance of apoptotic cellular fragments. 1236 38

In curatively resected gastric cancer, the incidence of distant relapse is as high as 30%. Although the most important factor contributing to the local control of the tumor is the microscopic tumor-free margin of the surgical resection, the occurrence of distant metastases is in many cases due to preoperative or perioperative tumor cell dissemination. In addition to the established TNM staging system, disseminated tumor cells may serve as independent prognostic factors influencing patient outcome after curative surgery. Basically, in gastric cancer three compartments have been identified in which single tumor cells may be shed: lymph nodes, peritoneal cavity, and bone marrow. Assessment of resected regional lymph nodes with monoclonal antibodies directed against cytokeratin antigens leads to an upstaging in comparison with conventional histology. Nodal micrometastases detected by immunohistochemistry result in an upstaging of up to 36% of patients. However, their prognostic significance remains controversial. Local dissemination of tumor cells in the peritoneal cavity determines the outcome in advanced gastric cancer and diffuse-type carcinoma. Patients with negative peritoneal washings seem to have a more favorable prognosis. Moreover, with the use of these diagnostic tools, patient subpopulations may be identified which profit from intraperitoneal therapy regimens. Diffuse hematogenous tumor cell dissemination into the bone marrow has been shown to be a prognostic factor in several studies. In our own population of 180 gastric cancer patients, bone marrow cells were screened immunohistochemically with a monoclonal antibody directed against cytokeratin 18 (CK18). In 95 patients (53%), CK2-posititve cells were detected. In a multivariate analysis, the independence of the presence of three or more disseminated tumor cells per 10(6) mononuclear cells was proven to be a prognostic factor in patients with intestinal-type tumors, pT1/2 status, and pN0 status. In conclusion, the TNM status only partially reflects the actual extent of systemic disease in patients with resected gastric cancer. The assessment of minimal residual disease is valuable in estimating the prognosis in many patients. In the future, staging systems will have to not only include TNM data but also provide specific information on biological properties of residual cancer cells in order to establish more exact prognostic estimates and provide patients with an individually tailored multimodal treatment.
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PMID:Minimal residual disease in gastric cancer. 1279 Mar 23

The sentinel node (SN) is the first lymph node in the lymphatic basin to be affected by metastasis from the primary tumour and is used to predict the status of the remaining nodes in the basin. We succeeded in detecting SNs of clinically early gastric cancers by intraoperative injection of a blue dye around the tumour. In the study presented here, multiple-marker reverse transcription-polymerase chain reaction (RT-PCR) was used to detect micrometastases in SNs and results were compared with those obtained with conventional histology. Expressions of cytokeratin-18 (CK-18), carcinoembryonic antigen (CEA), human telomerase reverse transcriptase (hTRT) and MUC-1 in SNs were determined by RT-PCR and Southern blot assay. Of the 213 SNs obtained from 35 cases of gastric cancer, eight nodes (3.8%) from five patients contained metastases that could be identified by conventional histology. However, CK-18 mRNA was expressed in 15 (7.0%), CEA in 12 (5.6%), hTRT in 10 (4.7%), and MUC-1 in 12 (5.6%) nodes, with at least one mRNA marker expressed in 25 nodes (11.7%) obtained from six patients. In the five patients with nodal metastases identified by conventional histology, two had metastases in both SNs and non-SNs. And, in the 30 patients without nodal metastases identified by conventional histology, one patient with micrometastases in the SNs identified by RT - PCR and Southern blot assay also had metastases in non-SNs as identified by serial sectioning and immunostaining of CK-18. All additional metastases were detected in non-SNs located in the same lymphatic basin as the previously detected SNs. This suggests that lymph node dissection of early-stage gastric cancer in the lymphatic basin may be mandatory even for patients without histologically detectable metastases in SNs.
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PMID:Micrometastases in sentinel nodes of gastric cancer. 1291 77


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