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)

The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size > or =2 cm, Ki67 proliferative index > or =2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 non-insulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan-Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P< or =0.0004) and tumor-specific death (P< or =0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index > or =2% were reliable in predicting a poor tumor-free survival in non-insulinoma EPTs (P< or =0.0181, whereas CK19 expression was the most optimal predictor of tumor-specific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in non-insulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.
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PMID:DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients. 1791 6

Circulating tumor cell (CTC) detection in peripheral blood of colon and other epithelial cancer patients is becoming a scientifically recognised indicator for the presence of primary tumors and/or metastasis. The resulting need to further develop CTC detection-based systems for improved diagnosis, prognosis and assessment of therapy efficacy in tumour patients has prompted the application of different approaches, including expression analysis of tissue-specific and epithelial genes. In this context, lack of specificity of the analysed genes remains a fundamental problem for reliable CTC detection. In this study, we have selected a panel of highly specific epithelial genes: cytokeratin 20 (CK20), cytokeratin 19 (CK19), carcinoembryonic antigen (CEA) and guanylyl cyclase C (GCC), and performed RT-PCR analysis to assess their expression in total blood and in different cell fractions of peripheral blood (PBMC and CD45-negative population) of cancer patients and healthy controls. Our results demonstrate that analysis of a single gene in a CTC-enriched population (CD45(-) peripheral blood cells) of cancer patients allows detection of a CTC molecular signature in at most 63.3% of cases, while analysis of all four genes performed in all three sample types increases the detection of positive patient samples to 87.7%. Healthy controls did not show positivity for any combination of these genes, although positivity was observed for the CEA marker alone, which was detected in 3 (6.6%) out of 45 donors, and only in the CD45(-) fraction. Here, we demonstrate that combined analysis of the genes above, in multiple blood fractions, results in a highly specific and sensitive CTC detection system in patients with metastatic solid tumors. Therefore, we believe that validation on a large scale of this approach, which demonstrates higher specificity in patients compared to controls, could become a relevant CTC screening test in patients with established metastatic disease, and furthermore, may also be useful for evaluating the possible presence of CTCs before the onset of clinically manifested metastatic spreading.
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PMID:Molecular signature detection of circulating tumor cells using a panel of selected genes. 1826 45

Axial chordoma represents approximately 1% of malignant bone tumors. This tumor expresses cytokeratins, specifically cytokeratin 19, and commonly S100. More recently brachyury, a transcription factor important in mesodermal differentiation, including notochord development, has been detected by immunohistochemistry in axial chordomas and hemangioblastomas but not chondrosarcomas or other neoplasms. In this report, we describe 10 cases (6 men, 4 women: age 18 to 68 y; mean 44.6) of extra-axial tumors, 8 in bone and 2 in soft tissue, with morphologic and immunohistochemical features identical to those of axial chordoma. Imaging excluded metastases from axial chordoma. Three tumors occurred in the tibia, the others in the rib, metatarsal, ulna, femur, pubis: 2 intracortical, 6 intramedullary. Both soft tissue brachyury-positive tumors, one involving the thumb the other the wrist, were sited in the juxta-articular region. Seven of the tumors were widely excised and these patients are disease-free but of the 3 tumors that recurred, 1 was curetted, 1 was marginally excised, and 1 had a pathologic fracture on presentation. Metastases have not occurred in any of the patients. We also confirm the expression of brachyury in hemangioblastomas, and for the first time demonstrates its expression in spermatogonia and testicular germ cell tumors by immunohistochemistry. Brachyury was not detected in a wide range of tumors including carcinomas, lymphomas, and sarcomas. In conclusion, we describe the first series of extra-axial skeletal chordomas bringing the total number of such cases reported in the literature to 11, and present the first report of 2 soft tissue chordomas as defined by brachyury expression.
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PMID:Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. 1830 Oct 55

At the Centre Oscar Lambret, the anticancer centre of the North of France, sentinel lymph node (SLN) procedures are routinely performed for localized (T0-T1, N0, M0) breast carcinoma without any previous treatment, in order to prevent the deleterious effects of axillary lymph node dissection. The present study was undertaken to assess if the expression in the tumor of a panel of 19 genes would allow to predict histological SLN involvement. We looked at cytokeratin 19 (CK19), mucin-1 (MUC1), mammaglobin (MGB1), cyclin D1 (CCND1), the four members of the HER/ErbB growth factor receptor family (EGFR, HER2-4), insulin-like growth factor-1 receptor (IGF-1R), estradiol receptors (ERalpha, ERbeta), progesterone receptor (PR), vascular endothelial growth factors (VEGF, VEGF-C), urokinase-like plasminogen activator (uPA), matrix metalloproteinases 2 and 9 (MMP2, MMP9), ets-related transcription factor ERM, and E-cadherin (CDH1). Their expression was quantified by real-time RT-PCR in 134 breast cancer samples and the relationships with SLN metastases were analyzed. A slight increase (35-40%) in CK19 and HER3 expression was observed in the tumors of patients with SLN metastases compared to those of patients without metastases, even if neither CK19 expression nor HER3 expression allowed to distinguish patients with micrometastases from patients with macrometastases. We conclude that the tumoral expression of biological parameters involved in cell proliferation or playing a critical role in the metastatic process, including tumor invasion and angiogenesis, is not strongly associated with SLN metastases.
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PMID:Real-time reverse-transcription PCR to quantify a panel of 19 genes in breast cancer: relationships with sentinel lymph node invasion. 1840 45

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins--including numerous keratins characterized only recently--are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family.
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PMID:The human keratins: biology and pathology. 1846 49

The purpose of our study was to demonstrate that distinct cytogenetic alterations in the most common subtype of renal cell cancer, clear cell renal cell carcinoma (ccRCC), are reflected in protein expression profiles. We performed conventional cytogenetics and immunohistochemical analysis for cytokeratins (CKs) on 126 ccRCCs. Protein expression was evaluated in situ using a semiautomated quantitative system. The results were validated using an independent cohort of 209 ccRCCs with long-term follow-up. Cytogenetic alterations were identified in 96 of 126 ccRCCs, most of them involving chromosome 3 through loss, deletion or translocation. Expression of CKs and E-cadherin in ccRCC was associated with lack of cytogenetic alterations and low nuclear grade. In the validation set, CK7 and CK19 protein expression was associated with better clinical outcome. At the multivariate level, the best model included metastatic status and CK19 expression. Expression microarray analysis on 21 primary ccRCCs and 14 ccRCC metastases identified genes significantly associated with CK7 and CK19 expressing ccRCCs. Two novel ccRCC biomarkers associated with the CK7 positive ccRCC phenotype, PMS2 and MT1-MMP (MMP14), were further validated. We conclude that the variability observed for CK expression in ccRCC can be explained by genetic heterogeneity. Distinct molecular subtypes of ccRCC with prognostic relevance were identified, and the CK7/CK19 expressing subtype is associated with better outcome.
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PMID:Association of cytokeratin 7 and 19 expression with genomic stability and favorable prognosis in clear cell renal cell cancer. 1847 71

Endometrial stromal sarcomas can be confused with several neoplasms because of their inconsistent and widely varied morphologic appearance and frequent immunohistochemical expression of a variety of antigens including cytokeratin. The resulting diagnostic challenge becomes problematic particularly in the diagnosis of metastases resulting from such tumors. Because of the sometime epithelioid appearance of the tumor cells and their expression of cytokeratin, the metastases may be misdiagnosed as poorly differentiated carcinoma. We therefore studied the profile of cytokeratin proteins expression in 17 cases of endometrial stromal sarcomas using a panel of antibodies including cytokeratin cocktail antibody (AE1/AE 3), CK5/6, CK7, CK14, CK16, Cam5.2 (CK8), CK19, CK20, and 34Ebeta12 (CK1, 5, 10, and 14). Of the 17 cases, 8 (47%) stained positive with the cytokeratin cocktail antibody (AE1/AE 3). Of the 8 cases with cytokeratin expression, 5 (63%) stained positive with CK19, and 3 of them stained positive with Cam5.2. The 3 cases that stained positive with Cam5.2 also expressed CK19. Of the 5 cases with CK19, 1 was focally positive for CK5/6, CK7, and 34Ebeta12. None of the cases expressed CK14, CK16, or CK20. These results show that CK19 is most commonly expressed cytokeratin in endometrial stromal tumors. Hence, the inclusion of CK19 in the panel of immunostains may help resolve the diagnostic confusion created by keratin expression in endometrial stromal sarcoma and may also help in the correct diagnosis of endometrial stromal sarcoma at extrauterine sites.
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PMID:Immunohistochemical profiling of cytokeratin expression by endometrial stroma sarcoma. 1861 44

The optimal pathological assessment of sentinel nodes (SLNs) in breast cancer is a matter of debate. Currently, multilevel histological evaluation and immunohistochemistry (IHC) are recommended, but alternative RT-PCR procedures have been developed. To assess the reliability of these different procedures, we devised a step-sectioning protocol at 100 micron-intervals of 74 SLNs using methacarn fixation. mRNA was extracted from sections collected from levels 4 to 5. Mammaglobin, CEA and CK19 were used for RT-PCR. mRNA extraction was successful in 69 SLNs. Of these, 7 showed macrometastases (>2mm), 2 showed micrometastases (<2 mm) and 7 showed isolated tumour cells (ITC) by IHC. RT-PCR was positive for the three markers in 6 of 7 macrometastases and in 1 of 2 micrometastases. In the 2 RT-PCR negative cases, metastases were detected only on sections distant from those analysed by RT-PCR. CEA and/or CK19 were positive by RT-PCR in 3 of 7 ITC and in 23 morphologically negative SLNs. In conclusion, the main goal of our study was to show that the use of alternate sections of the same sample for different procedures is the key reason for the discrepancies between molecular and morphological analyses of SLN. We believe that only prospective studies with quantitative mRNA analysis of specific metastatic markers on the whole lymph node can elucidate the utility of molecular assessments of SLN.
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PMID:Technical limits of comparison of step-sectioning,immunohistochemistry and RT-PCR on breast cancer sentinel nodes: a study on methacarn-fixed tissue. 1867 55

Tumor to tumor metastasis is a rare, but well recognized entity, most commonly involving a carcinoma metastasis to a benign or low grade mesenchymal tumor. A case of breast carcinoma metastasis in a recurrent myxoid liposarcoma is presented in this study. A 52-year-old female patient with a history of breast carcinoma (70% invasive lobular carcinoma and 30% invasive ductal carcinoma) presented with a mass in the right lumbar region. The excised mass was diagnosed as myxoid liposarcoma. The tumor recurred twice and was reexcised. Microscopic examination of the second recurrence revealed multiple foci of breast carcinoma metastases in myxoid liposarcoma. Immunohistochemical study showed staining for CK19, GCDFP-15, estrogen and progesterone in metastases. Both breast carcinoma metastasis and myxoid liposarcoma were immunoreactive for E-cadherin and beta-catenin. To our knowledge, this is the first reported case of breast carcinoma metastasis in myxoid liposarcoma, and the first occurrence of metastasis in a liposarcoma.
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PMID:Breast carcinoma metastasis in recurrent myxoid liposarcoma. 1898 96

Comparison of the sensitivity of cytological and molecular genetic methods (19 specimens of lymph nodes from 8 patients with breast cancer and suspected metastases obtained by transcutaneous fine-needle aspiration biopsy under ultrasound guidance) showed that molecular genetic and cytological studies produced true results in 95 and 84% specimens, respectively. True-positive and true-negative results were obtained in 8 and 7 patients, respectively. Expression of cytokeratin 19 was detected in 3 specimens with negative cytological results and confirmed metastases in lymph nodes. Our results indicate that molecular genetic diagnostic study for lymph node metastases should be used in small amounts of biopsy specimens, presence of marginal metastases in lymph nodes, and negative results of repeated cytological examination.
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PMID:Cytokeratin 19 mRNA concentration in lymph nodes as a diagnostic marker of metastases. 1902 12


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