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)

Neuroendocrine lung tumors (NELT) from 50 patients were studied immunohistochemically. Malignant carcinoid and small-cell lung carcinoma (SCC) have a higher level of apoptosis than ordinary carcinoid. An increase of apoptosis index in NELT coincides with an increase in NELT proliferative activity (Ki-67, Bcl-2, c-myc, p-53) as compared to a typical carcinoid. Phagocytosis of apoptotic bodies was absent in SCC. Classic SCC differs from combined SCC by a higher apoptosis index and lower expression of p-53 and Bcl-2. Metastatic SCC differs from SCC without metastases by lower apoptosis level and higher level of proliferative indices (Ki-67, Bcl-2) of tumor cells. Development of unbalance between apoptosis and proliferation may result from mitosis and apoptosis pathology.
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PMID:[Small cell carcinoma and carcinoids of the lung: morphology of apoptosis and expression of biomolecular markers of tumor growth]. 1107 93

Amplification and overexpression of the c-myc gene have been associated with neoplastic transformation in a plethora of malignant tumours. We applied interphase fluorescence in situ hybridization (FISH) with a locus-specific probe for the c-myc gene (8q24) in combination with a corresponding chromosome 8 alpha-satellite probe to evaluate genetic alterations in 8 primary melanomas and 33 advanced melanomas and compared it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin. Additionally, in metaphase spreads of 7 melanoma cell lines a whole chromosome 8 paint probe was used. We investigated the functionality of the c-myc gene by detecting c-myc RNA expression with RT-PCR and c-myc protein by immunohistochemistry. 4/8 primary melanomas and 11/33 melanoma metastases showed additional c-myc signals relative to the centromere of chromosome 8 copy number. None of the nevi, safety margins or normal skin samples demonstrated this gain. In 2/7 melanoma cell lines (C32 and WM 266-4) isochromosome 8q formation with a relative gain of c-myc copies and a loss of 8p was observed. The highest c-myc gene expression compared to GAPDH was found in melanoma metastases (17.5%). Nevi (6.6%) and primary melanomas (5.0%) expressed the c-myc gene on a lower level. 72.7% of the patients with c-myc extra copies had visceral melanoma metastases (UICC IV), patients without c-myc gain in 35.0% only. The collective with additional c-myc copies also expressed the gene on a significantly higher level. These results indicate that a c-myc gain in relation to the centromere 8 copy number might be associated with advanced cutaneous melanoma.
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PMID:Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases. 1113 16

Metastasis and invasion are key steps in the systemic spread of tumor cells. To identify the genes involved in this process we recently selected highly invasive and weakly invasive cell clones from a melanoma cell line. Both cell clones showed a stable phenotype over more than 40 passages and previous analyses revealed a fivefold difference in their invasive potential in vitro and in tumorigenesis in vivo. To compare gene expression of the two cell clones a cDNA array system (Clontech human cancer cDNA array) was used. Exact quantification of differentially expressed genes in each cell clone was performed by real-time RT-PCR. An evaluation of the array data revealed a total of 36 genes that were more than 1.5-fold differentially expressed, and 26 (72%) of these showed a differential expression pattern by quantitative RT-PCR. Previously known differences in expression patterns, including loss of p16 and HLA I, or equal expression of p73, and RAR alpha, beta and gamma were confirmed by the array data. In addition, reduced expression levels of several cytoskeletal proteins, such as vimentin, gamma-actin, desmin and cytokeratins, in the highly invasive cell clone were reproducibly identified. Other genes strongly upregulated in the highly invasive cell clone included jagged 2, STAT1, tPA and c-myc, whereas MDA-6 (p21), caspase 2 and semaphorin were found to be downregulated. In conclusion, comparative hybridization of cDNA arrays identified a series of novel invasion-associated changes in gene expression and confirmed previously known expression patterns.
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PMID:Isolation of invasion-associated cDNAs in melanoma. 1148 May 87

A significant number of patients with liver metastases from colorectal cancer (CRC) achieve 5-year survival after liver resection. Increased expression of genetic markers in the primary tumor are known to predict outcome after colonic resection, but the predictive value of such markers after resection of hepatic metastases is unknown. The objective of this study was to evaluate whether DNA content and multiple genetic markers, separately or expressed together, can predict patient outcome (liver recurrence and survival) after resection of hepatic metastases. We studied the paraffin-embedded liver tissue of 71 consecutive patients who had undergone a potentially curative resection of hepatic metastases from CRC. Using DNA flow cytometry and immunohistochemical staining techniques we determined the DNA content and the level of co-expression of seven tumor-associated proteins: proliferating cellular nuclear antigen (PCNA), epidermal growth factor receptor (EGFr), p53, c-erbB-2, H-ras, c-myc, and nm23. Three endpoints (liver recurrence, cancer specific, overall survival) were correlated with these tumor markers. The 5-year overall survival of the group was 31.2%. There was no correlation detected between the DNA aneuploidy and overall or cancer-specific survival. Similarly, expression of the individual tumor-associated proteins did not predict survival. Patients whose tumors co-expressed multiple markers had survivals similar to those whose tumors expressed fewer markers. However, a significant difference in hepatic recurrence was found between the p53-positive and p53-negative patients (p = 0.007), with marker-negative tumors having decreased recurrence. In conclusion, this study demonstrates that the DNA content and genetic markers c-myc, c-erbB-2, EGFr, H-ras, p53, PCNA, and nm23 do not predict survival after potentially curative resection of hepatic metastases from CRC. However, the immunoreactivity of p53 may be an important marker of local recurrence in the liver, which may be useful if re-resection of metastatic liver tumors is considered a viable management option in this disease.
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PMID:Genetic markers of survival and liver recurrence after resection of liver metastases from colorectal cancer. 1157 82

Overexpression of c-myc protein and amplification of c-myc were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues, respectively. Overexpression of c-myc was detected in 45% (199/440) and amplification of c-myc was observed in 25% (112/440) of the primary breast carcinomas. Immunolocalization of c-myc oncoprotein was demonstrated in 35% (8/23) of the comedo subtype, 17% (3/18) of the non-comedo subtype, 37% (15/41) of the comedo DCIS and 49% (20/41) of the adjacent invasive ductal carcinomas, 21% (4/19) of the non-comedo DCIS and 37% (7/19) of the adjacent invasive lesions, 49% (133/270) of the invasive ductal carcinomas, 33% (11/33) of the invasive lobular carcinomas, 29% (6/21) of the colloid carcinomas and 47% (7/15) of the medullary carcinomas. C-myc was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 24% (10/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 21% (7/33) of the invasive lobular carcinomas, 14% (3/21) of the colloid carcinomas and 24% (4/15) of the medullary carcinomas. Amplification of c-myc was noted in 16% (3/9) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. A significant association (P<0.05) was observed between in situ components and adjacent invasive lesions for c-myc expression and amplification. Overexpression of c-myc protein was significantly correlated with poorly differentiated (P<0.05) and high proliferation index (Ki-67) (P<0.05) tumors but not with lymph node metastases (P>0.05), patient age (P>0.05) and estrogen receptor status (P>0.05). Significant relationship was also noted between amplification of c-myc and absence of estrogen receptor (P<0.05), high histological grade (P<0.05) and high proliferation index (Ki-67) (P<0.05). No relationship was seen with nodal status (P>0.05) and patient age (P>0.05). Majority of the Malaysian female patients are from younger age group (<50 years old) but overexpression and amplification of c-myc was not statistically associated with patient age (P>0.05) indicating that these alterations may be independent events of patient age. The above observations suggest that overexpression and amplification of c-myc could play an important role in tumor progression from non-invasive to invasive and, also, it may have the potential as a marker of poor prognosis of breast cancer.
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PMID:Protein expression and molecular analysis of c-myc gene in primary breast carcinomas using immunohistochemistry and differential polymerase chain reaction. 1178 32

To determine whether genetic changes are markers of cancer progression and patient survival in Stage T(2-3)N(1-3)M(0) prostatic carcinoma, we compared 26 patients who died of tumor relapse after prostatectomy and lymphadenectomy (case group) with 26 matched patients who were alive at the time of the matched case's death (control group). Nine unmatched cases were also included in this study. In 37 cases, paired primary tumors (119 foci) and lymph node metastases (114 foci) were available for study. Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, and 17 and region-specific probes for D7S486 (7q31), c-myc (8q24), LPL (8p22), and p53 (17p13) was performed on available primary carcinomas and lymph node metastases. In primary tumor foci, +7q31, -8p22, +c-myc, substantial additional increases of myc (AI-c-myc), and -p53 were observed in 65%, 74%, 43%, 29%, and 31% of foci, respectively. AI-c-myc was strongly associated with higher cancer Gleason score (P =.003). Heterogeneity of genetic changes was frequently observed among multiple cancer foci. Lymph node metastases of prostate cancer usually shared genetic changes with paired primary tumors. In addition, the genetic change pattern with -8p, +c-myc or AI-c-myc, +7q, and +p53 was slightly higher in lymph node metastases (22%) than in primary tumors (6%) (P =.08). In matched case and control patients, simultaneous gain of 7q31 (+7q31) and CEP7 (+CEP7) was identified in 59% and 68% of specimens for case and control groups, respectively (P =.48). Loss of 8p22 (-8p22) was identified in 77% and 69% of specimens for case and control groups, respectively (P = 1.0). Simultaneous gain of c-myc (+c-myc) and CEP8 (+CEP8) without overt additional increase of c-myc copy number relative to CEP8 copy number, was identified in 38% and 54% of specimens for case and control groups, respectively (P =.27). AI-c-myc was identified in 54% and 23% of specimens for case and control groups, respectively (odds ratio = 3.0, P =.06). Loss of p53 (-p53) was identified in 46% and 15% of specimens for case and control groups, respectively (odds ratio = 4.0, P =.04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T(2-3)N(1-3)M(0) prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T(2-3)N(1-3)M(0) prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.
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PMID:Loss of p53 and c-myc overrepresentation in stage T(2-3)N(1-3)M(0) prostate cancer are potential markers for cancer progression. 1179 39

This report presents magnetic resonance imaging (MRI) findings of a breast carcinoma metastasis in an intracranial meningioma with correlated pathological findings. MRI showed multiple foci of intense enhancement with hypointense surrounding areas. The described foci appeared to be metastatic disease from the patient's known breast carcinoma. In addition, this is the first study reported in the literature to have investigated the expression of a possibly common carcinogenic molecule in breast carcinoma metastatic to a coexisting meningioma: overexpressed c-myc oncogene was found both in the breast carcinoma compartment and in the meningioma component of the tumor.
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PMID:Tumor in tumor: metastasis of breast carcinoma to intracranial meningioma. 1198 98

Searching for ways to improve the characterization of breast cancer we examined the relationship between the status of the FHIT gene transcript and amplification of c-myc and the c-erbB2 oncogene. Abnormal FHIT transcript was detected in 32 of 79 cancers examined. The presence of Fhit protein estimated by Western blots was evident only in cancers exhibiting a normal-sized FHIT transcript. This indicates that abnormal FHIT transcripts observed in our study did not encode any Fhit protein or the amount of such protein was very low. There was no association between the presence of aberrant FHIT gene transcript with age, tumor size, estrogen and progesterone receptor status, local metastases and histological grading. However, the abnormalities in FHIT gene transcripts were observed with different frequency depending on the histopathological type of the tumor. The aberrant FHIT transcript was detected in 60% of lobular cancers and only in 28% of ductal cancers. Analyzing the occurrence of c-myc and c-erbB2 amplification and the presence of aberrant FHIT gene transcripts we found that the aberrant FHIT transcript more frequently occurred in tissues with c-myc amplification. There was a significant (P < 0.05) correlation between the occurrence of the aberrant FHIT gene transcript with accompanying c-myc amplification and positive lymph node status. However, in order to evaluate the predictive value of these findings in breast cancer, an extended clinical follow up will be necessary.
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PMID:Abnormal FHIT gene transcript and c-myc and c-erbB2 amplification in breast cancer. 1236 75

Although the expression of the metastases-associated gene MTA1 correlates with tumor metastases, its role in regulating type IV collagenase expression is unknown. Enforced MTA1 expression in HT1080 cells reduced basal and 12-myristate 13-acetate-induced 92-kDa type IV collagenase (MMP-9) protein/mRNA levels. DNase I hypersensitivity and PstI accessibility assays revealed multiple regions of the MMP-9 promoter (-650/-450 and -120/+1), showing reduced hypersensitivity in the MTA1-expressing cells. Chromatin immunoprecipitation assays demonstrated MTA1 binding to the distal region, which spans several regulatory cis elements. Co-immunoprecipitation and chromatin immunoprecipitation assay experiments revealed histone deacetylase 2 (HDAC2)-MTA1 protein-protein interactions and the MTA1-dependent recruitment of HDAC2 to the distal MMP-9 promoter region, yielding diminished histone H3/H4 acetylation. However, HDAC2 binding and H3/H4 acetylation at the proximal MMP-9 region were unaffected by MTA1 expression. Furthermore, trichostatin treatment only partially relieved MTA1-repressed MMP-9 expression, indicating a HDAC-insensitive component possibly involv ing the nucleosome-remodeling Mi2 activity, which was recruited to the promoter by MTA1. In summary, (a) MMP-9 adds to a short list of MTA1-regulated genes, which so far only includes c-myc and pS2, and (b) MTA1 binds to the MMP-9 promoter, thereby repressing expression of this type IV collagenase via histone-dependent and independent mechanisms.
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PMID:Repression of 92-kDa type IV collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism, which is both dependent on and independent of histone deacetylation. 1243 81

Apoptosis is an important co-factor in the pathogenesis of a plethora of malignancies. Enhanced c-myc activation can result either in proliferation or apoptosis. Coexpression with antiapoptotic bcl-2, which abrogates the apoptotic function of c-myc might lead to an enormous growth advantage of cells. In order to elucidate the role of c-myc and bcl-2 as well as the coexpression of both genes in human melanoma, their expression was studied in four samples of normal skin (SK), 15 surgical margins (SM), 20 benign melanocytic nevi (MN), 20 primary melanomas (MM), and 30 melanoma metastases (MMET) by RT-PCR. These results were compared with immunohistochemistry (IH) in 7 SK, 7 SM, 26 MN, 50 MM, and 34 MMET. Similar results were found with both methods. However, MMET expressed c-myc (PCR 28/30, IH 23/34) as well as bcl-2 (PCR 27/30, IH 24/34) more frequently. Primary melanomas showed a similar expression pattern as SM and nevi. Moreover, in contrast to SK, SM, MN, and MM coexpression of bcl-2 and c-myc was found more frequently in MMET (PCR 25/30, p < 0.01, IH 19/34, p < 0.01). These results indicate that coexpression of c-myc and bcl-2 appears to be associated with advanced melanoma and contributes to the malignant phenotype.
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PMID:Expression of c-myc and bcl-2 in primary and advanced cutaneous melanoma. 1244 22


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