Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), and of their receptors (EGFR and PDGFR) was immunohistochemically examined in 37 cases of osteosarcoma. Furthermore, immunostaining for p53 protein and Ki-67 antigen by MIB-1 was carried out and compared with the above results. EGFR (81%) expressed more often than EGF (51%) and the expression of EGF and EGFR, and PDGF and PDGFR were recognized in 49% and 38%, respectively. In eleven cases (30%), the expression of both growth factors and their receptors was combined. Anaplastic osteosarcoma showed higher MIB-1 index than osteoblastic and fibroblastic subtypes (P < 0.05). High grade osteosarcomas (G3 and G4) revealed higher MIB-1 index compared with low grade tumors (G1 and G2). PDGF positive tumors (MIB-1 index: 20.0) showed significantly higher proliferation compared with PDGF negative tumors (MIB-1 index: 6.5) (P < 0.01). Five out of 37 cases (13.5%) showed positive immunoreaction for p53. There was no correlation of p53 status with MIB-1 index and the expression of growth factors or their receptors. Our results suggest that PDGF expression may be an important mediator of cell proliferation control, via an autocrine mechanism, in human osteosarcoma.
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PMID:Expression of growth factors and their receptors in human osteosarcomas. Immunohistochemical detection of epidermal growth factor, platelet-derived growth factor and their receptors: its correlation with proliferating activities and p53 expression. 854

Primary cerebral lymphomas (PCL's) are rare tumors which, however, occur with increasing frequency. The present study investigated 55 PCL's of B-cell type, 36 in immunocompetent and 19 in AIDS-patients and 6 cases of intravascular lymphomatosis. In immunocompetent patients, proliferative indices as evaluated by PC10 and MIB1 reflected the histologic grade. Low grade tumors had a mean PCNA and MIB-1 count of 19 and 18.8 (SD 14.7 and 13.2), respectively, and high grade neoplasias showed counts of 56.7 and 47.1 (SD 19 and 17.4), respectively. No correlation of both indices with patient survival was found. 21 cases (58.3%) displayed p53-positivity of varying degree and 19 cases (52.7%) harbored bcl-2 positive neoplastic cells. Immunocompetent cases were always negative for Epstein-Barr virus RNA and lmp-1-protein. In AIDS-cases, 13 cases (68.4%) showed up lmp-1 positivity and 15 cases (78.9%) had EBER-RNA. bcl-2 positive cells were detected in 5 cases (26.3%) and all cases were p53-negative. These results are in keeping with a role of EBV in the pathogenesis of primary cerebral lymphomas in AIDS-, but not in immunocompetent patients. None of the cases with intravascular lymphomatosis showed an expression of bcl-2 or p53 oncoproteins or lmp-1 and none had EBER-RNA.
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PMID:Primary non-Hodgkin lymphomas of the CNS-proliferation, oncoproteins and Epstein-Barr-virus. 870 88

Prostatic adenocarcinoma with a signet ring cell (SRC) component is a rare, incompletely characterized variant that must be distinguished from similar tumors of bladder or gastric origin. In this study, we used mucin and immunoperoxidase stains on formalin-fixed, paraffin-embedded sections from 12 prostatic adenocarcinomas with SRC components, with antibodies to prostate-specific antigen (PSA), cytokeratins, MIB-1, bcl-2, c-MET, CD44v6, and CD44v7; we performed a comparison study on six bladder and seven gastric carcinomas with SRCs. The prostatic SRC component was always associated with the usual high-grade adenocarcinoma. Both components were positive for PSA, AE1/AE3, and CAM 5.2 (12 cases of 12) and also expressed c-MET (5 cases of 9), CD44v6 (9 of 10), and CDv7 (9 of 10). Only rare cells stained for bcl-2 (3 cases of 9). The mean MIB-1 proliferation index was 8%. Intracellular mucin was identified (periodic acid-Schiff with diastase predigestion (PAS-D) in 9 cases of 10, mucicarmine in 5 of 10, alcian blue in 6 of 10). Bladder and gastric tumors were positive for PSA (3 cases of 6 and 2 of 7, respectively), using a polyclonal antibody, and for bcl-2 (5 cases of 6, 2 of 7), c-MET (6 of 6, 6 of 7), CD44v6 (5 of 6, 6 of 7), and CD44v7 (4 of 6, 4 of 7), with mean MIB-1 proliferation indices of 15 and 35%, respectively. All were negative for cytokeratin 34 beta E12. We conclude that prostatic adenocarcinomas with SRC components are typically accompanied by high-grade adenocarcinoma; are variably positive for mucin, with PAS-D being the most sensitive stain; show expression of PSA, cytokeratins, MIB-1, bcl-2, c-MET, and CD44 similar to that shown by high-grade adenocarcinoma components; have a low MIB-1 proliferation index; and are not always distinguishable from SRC components of bladder and stomach carcinomas with any of the above stains, including PSA.
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PMID:Prostatic carcinoma with signet ring cells: a clinicopathologic and immunohistochemical analysis of 12 cases, with review of the literature. 964 93

Conventional histopathological criteria based on light microscopy are used in pulmonary oncologic pathology in order to establish the diagnosis of tumor, but most frequently they are insufficient, accurate diagnosis requiring ultrastructural and immunohistochemical investigations. The method of immunostaining allowed some molecular marker to be evaluated. Some of them seem to be important in carcinogenesis as a general process, while others have high specificity for lung tumors. Estimation of EGFR and c-erbB-2 protein immunoreactivity showed a significantly stronger staining with NSCLC and was correlated to the poor differentiation of the tumors, undergoing an aggressive biological behavior and an unfavorable prognosis. The expression of p53 protein was found in 19 cases by immunostaining with DO-7 antibody. Immunotracing of more than 50% of the tumoral cells was a predictive factor for the progression of the disease. The growing rate of tumoral proliferative activity was evaluated by immunotracing technique (MIB-1), allowing the Ki-67 index of labeling to be calculated.
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PMID:Immunohistochemical markers in the morphological diagnosis of lung carcinoma. 974 20

Mitogen-activated protein kinase (MAPK) is a serine-threonine kinase that is activated by various extracellular stimuli. Extracellular signal-regulated kinases (ERK1 and ERK2), an MAPK subfamily, are activated by many oncogenes, such as ras and raf, and they induce cell proliferation. myc is also an oncogene and one of the targets of ERKs. Mutations of ras and overexpression of myc were found in various human cancers, and ERKs were also reported to play a role in carcinogenesis. In this study, we examined 39 biopsy specimens of oral squamous cell carcinoma (OSCC) and 5 of normal gingival mucosa for the expression of ERK protein and the proliferation marker, MIB-1 (Ki-67 antibody). Thirteen OSCC specimens and five normal gingival biopsies were also examined for the expression of ERKs mRNA by in situ hybridization. Double staining for ERKs and MIB-1 was also performed. Histologically, 18 patients (46%) were diagnosed with well-differentiated SCC, 17 (44%) with moderately differentiated SCC, and 4 (10%) with poorly differentiated SCC. The histologic grade correlated with the MIB-1 index. The localization of ERK1 was similar to that of ERK2. Positive signals for ERK proteins were localized in superficial keratinocytes in normal gingival mucosa, whereas these mRNAs were weakly positive in the basal and spinous layer. Basal and suprabasal cells were positive for MIB-1. In well-differentiated and moderately differentiated OSCC, positive signals for ERK mRNA and proteins were found at higher levels than in normal gingival mucosa in keratotic cells around cancer pearls. Some cells showed positive signals for ERKs and MIB-1. Furthermore, most cancer cells in poorly differentiated SCC were positive for both ERK and MIB-1. The histologic grade was statistically related to the percentage of cells positive for both ERK and MIB-1. This suggested that ERKs might be related to proliferation in OSCC.
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PMID:Overexpression of the ERK/MAP kinases in oral squamous cell carcinoma. 975 69

Summarizing the current evidence regarding the usefulness of the previous markers for predicting patient outcome, the most promising proliferation marker for predicting patient outcome in patients with brain tumors appears to be KI-67/MIB-1. Its potential usefulness appears to be greatest (1) for grade II and III astrocytic and oligodendroglial tumors in adults, where it may potentially predict length of survival; (2) for nonpilocytic gliomas in children, where it may also potentially predict survival; and (3) for benign, completely resected meningiomas, where it may potentially predict tumor recurrence. Although MIB-1 shows potential, we do not believe there is evidence yet definitely to consider MIB-1 labeling index a predictor of prognosis in these tumors due to the lack of published prospective studies validating the preliminary findings of multiple investigators who have performed only single-center retrospective studies. We also believe that the exact use of MIB-1 labeling index as an independent prognostic indicator for any type and grade of tumor may be complex, given the fact that all of these brain tumors have multiple independent prognostic factors contributing to patient outcome, many of which are readily available clinical factors. In the present managed care environment, MIB-1 labeling should probably await demonstration that it significantly contributes to the physician's ability accurately to predict patient outcome. The presence of telomerase RNA or telomerase activity appears to correlate with degree of malignancy in multiple types of brain tumors, including gliomas; however, it currently has no use as an independent prognostic indicator of patient outcome. It may instead be a marker for malignant tumor initiation or progression. p53 and EGFR are molecular markers that show promise as prognostic indicators of recurrence-free and overall survival in patients with GBMs, but further prospective studies are needed to confirm the retrospective findings. Postsurgical evaluation of these markers is potentially helpful in planning follow-up and treatment for these patients, those patients having tumors expressing relatively high levels of these markers requiring closer follow-up and, when possible, more aggressive therapies. Despite intensive investigation into the expression of molecules regulating apoptosis in brain tumors, no evidence presently exists to support their usefulness as markers of patient outcome. This also applies to measurements of the apoptotic rate itself in human brain tumors. Our overall impression, therefore, is that despite our great desire to find the Holy Grail of patient prognosis in the measurement of a single molecular marker with a precise cut-off value, one has not been identified ... yet! If we allow ourselves to think in terms of organismal biology, it is not surprising that the attempt directly to correlate one or even five (MIB-1, telomerase, BCL-2, p53, EGFR) gene products with a phenomenon as complex as a patient's long-term survival is unrealistic. More likely, multiple pieces of clinical information (which we already know significantly impact patient outcome in patients with brain tumors) will be considered in conjunction with new, scientifically proved molecular information as it becomes available, allowing us to predict, ever more accurately, a given patient's clinical course and outcome.
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PMID:Implications of prognostic markers in brain tumors. 1057 18

The hepatocyte growth factor (HGF)/c-MET signaling system plays an important role in the carcinogenesis of various organs. We investigated the expression of HGF and its receptor c-MET by immunohistochemistry (IHC) in 69 cases of synovial sarcoma and compared the findings with clinicopathologic parameters, proliferating activities evaluated by MIB-1 labeling index (MIB-1 LI), and patients' prognosis. Furthermore, mRNA analysis of HGF, c-MET, and SYT-SSX fusion gene was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 concordant frozen materials. Twenty-one of 69 (30.4%) tumors showed positive reaction for c-MET, whereas 22 tumors (31.9%) were positive for HGF. In 10 cases, co-expression of HGF and c-MET was observed; however, there was no significant correlation between HGF and c-MET expression. HGF expression was correlated with female patients, large tumors (more than 5 cm), the presence of rhabdoid cells, low frequency of mast cells (<20/10 HPF), high nuclear grade (grade III), and high American Joint Committee (AJC) stage (III and IV). Conversely, c-MET expression was only correlated with large tumors. However, the coexpression of HGF and c-MET was significantly correlated with large tumor size, the existence of rhabdoid cells, and high AJC stage. Both the expression of HGF and the co-expression of HGF and c-MET showed a significantly high MIB-1 LI and were correlated with poor prognosis according to univariate analysis. Multivariate Cox analysis showed that high AJC stage, the expression of HGF, and a high MIB-1 LI (12.0>) independently had a negative impact on overall survival. In 22 frozen material cases evaluated by both IHC and RT-PCR, a statistically significant correlation was found between the 2 techniques. SYT-SSX fusion transcripts were detected in all 22 cases. Three tumors had SYT-SSX2 fusion transcripts, whereas 19 had SYT-SSX1 phenotype. Our results suggest that HGF/c-MET paracrine signaling may contribute to tumorigenesis and progression in synovial sarcoma.
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PMID:Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma. 1068 32

We report on a rare distinctive variant of infiltrating ductal carcinoma characterized by sebaceous differentiation of tumor cells. The neoplasm was identified in a lumpectomy specimen from a 45-year-old woman with extensive metastatic disease. In addition to conventional in situ and invasive ductal components, approximately half of the tumor cells exhibited a phenotype resembling tumors of the sebaceous skin appendage with coarsely vacuolated cytoplasm and peripherally displaced nuclei. The sebaceous moiety was also present in the distant metastatic deposits. There was no evidence of mucin production by tumor cells. Ultrastructurally, empty-appearing non-membrane bound vacuoles attested to the sebaceous cells' lipid content. The immunoprofile of the lesion included positivity for cytokeratin and epithelial membrane antigen. Vimentin, S100 protein and carcinoembryonic antigen were not expressed. Most tumor cell nuclei reacted with antibodies to oestrogen and progesterone receptors but failed to show overexpression of the HER2/neu protein. The MIB-1 labeling index averaged 16%. At variance with sebaceous breast carcinomas on record, the present case is notable for its prolonged clinical course.
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PMID:Sebaceous carcinoma of the breast. 1069 80

Topoisomerase IIalpha (topo IIalpha) plays a key role in DNA replication and is a target for multiple chemotherapeutic agents. In breast cancer, topo II expression has been linked to cell proliferation and HER2/neu protein overexpression. However, its relationship with outcome variables is not well established. Formalin-fixed, paraffin-embedded primary breast cancers from 184 women (mean age, 60 years) were stained for topo II by automated immunohistochemistry. A topo II expression index (TI) was determined by counting the number of positive cells per high-power field and calculating an overall mean number of positive cells per high-power field. Tumors with a TI of more than 1 were considered positive, and those with a TI of 1 or less were considered negative. A cell proliferation index was determine d by automated immunohistochemistry using the MIB-1 antibody in an identical technique. HER-2/neu gene amplification (HER-2 amp) was determined by automated fluorescence in situ hybridization using the Ventana unique sequence probe. Fifty-nine (32%) of the tumors had a TI greater than 1. On univariate analysis, increased topo II expression correlated with decreased patient survival (p = .001), advanced tumor stage (p = .034), lymph node metastasis (p = .018), and HER-2 amp (p = .016). Tumor stage (p < .0001), node-positive status (p < .0001), tumor grade (p = .025), HER-2 amp (p < .0001), and MIB-1 overexpression (p = .002) also correlated with survival on univariate analysis. Topo II expression did not correlate with tumor size, grade, estrogen receptor/progesterone receptor status, or disease recurrence. On multivariate analysis, stage (p < .0001), lymph node metastasis (p < .0001), and tumor grade (p = .002) all independently predicted disease-related death. Increased topo II expression is associated with an aggressive form of breast cancer featuring HER-2 amp and predicts disease-related death, lymph node metastasis, and advanced tumor stage.
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PMID:Topoisomerase IIalpha expression in breast cancer: correlation with outcome variables. 1082 26

Changes in morphological features between the primary and metastatic sites in osteosarcoma and the role of nm23 protein and c-MET oncogene product have remained controversial. In addition to histological studies, we evaluated the expression of nm23, c-MET, p53, and MDM2 immunohistochemically using 25 osteosarcomas in which both primary and concordant metastatic specimens were available. Moreover, we assessed proliferative activity using the monoclonal antibody MIB-1. Among these 25 cases, 4 tumors that were osteoblastic type (16%) in the primary site had changed morphologically to MFH-like type in the metastatic site, whereas 2 MFH-like type and 1 small cell-type tumors had changed to osteoblastic type. MIB-1 LI was significantly higher in the metastatic site than in the primary site (primary, 20.02; metastatic, 26.72; P = .0209). Seventeen cases (68%) showed increased nm23 expression in the metastatic site, whereas 2 cases showed reduced expression. nm23 expression was significantly increased in the metastatic site, compared with the primary site (P = .0009). Seven cases (28%) showing negative reaction for c-MET in the primary site showed immunuoreactivity for c-MET in the metastatic site. Although there was no statistical significance, c-MET expression seemed to be more frequent in the metastatic site, compared with the primary site. Among the overall tumors, c-MET-positive tumors showed significantly higher MIB-1 LI, compared with c-MET-negative tumors (negative, 20.99; positive, 27.65; P = .0292). No significant change was observed regarding p53 and MDM2 between the primary and metastatic site. Our results suggest that rather than being a metastasis-suppressor gene, nm23 is in fact correlated with metastatic progression in osteosarcoma. Positive correlation between c-MET expression and proliferative activity also suggests that c-MET expression may play an important role in tumor progression in osteosarcomas.
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PMID:Comparison of histological changes and changes in nm23 and c-MET expression between primary and metastatic sites in osteosarcoma: a clinicopathologic and immunohistochemical study. 1087 65


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