Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Prognostic biomarkers are lacking, and treatment has limited effect on survival. Tissues from Surveillance, Epidemiology, and End Results registries (Iowa, Hawaii, and Los Angeles) were used to build a tissue microarray of 161 pancreatic tumors (113 resections and 48 biopsies). Proportional hazard models adjusted for age, race, sex, stage, time-period of diagnosis, and treatment. Associations were examined between markers (MUC1, MUC2, MUC5AC, synaptophysin, chromogranin, neuron specific enolase, epidermal growth factor receptor, HER2, CD5, CD138, CK5/6, CK19, CK20, and p53) and survival time from diagnosis. After adjusting for covariates, borderline statistically significant associations were seen between expression of each of the three mucins (MUC1, MUC2, and MUC5AC) and shorter survival time. The associations strengthened for 154 (96%) adenocarcinomas, particularly the 120 (75%) well-differentiated to moderately differentiated ductal adenocarcinomas, a tumor type that occurred more often in the cohort among White cases than cases of other racial origin (P<0.01). For differentiated ductal adenocarcinomas, associations with shorter survival time were seen for expression of all three mucins combined versus other mucin expression patterns (adjusted hazard ratio, 1.8; 95% confidence interval, 1.2-2.6) and for MUC2(+) versus MUC2(-) expression (adjusted hazard ratio, 1.6; 95% confidence interval, 1.1-2.4). Mucin gene expression, particularly MUC2 expression, may have prognostic value for differentiated adenocarcinomas. Tumor histologies differed in this and Japanese cohorts. The tissue microarray is available to evaluate other biomarkers. Tissue-based surveillance can be used to monitor tumor histology in populations and facilitate applied research.
...
PMID:Associations between selected biomarkers and prognosis in a population-based pancreatic cancer tissue microarray. 1927 52

There is dearth of studies that provide a practical working formulation of breast cancer gene expression analysis for the surgical pathologist. ER, PR, HER2 were used as surrogate markers to classify 205 breast carcinomas into molecular classes. Ki-67 labeling index was calculated using an image analysis system. The data was analyzed for molecular class prevalence, and inter-relationships amongst morphologic parameters, Ki-67 index, and molecular classes. Of the 205 tumors, 113 (55%) were classified as luminal A (strong ER+, HER2 negative), 34 (17%) as luminal B (weak to moderate ER+, HER2 negative), 32 (15%) as triple negative (negative for ER/PR and HER2), 8 (4%) as ERBB2 (negative for ER/PR but HER2+), 10 (5%) as luminal A-HER2 hybrid (strong ER+ and HER2+), and 8 (4%) as luminal B-HER2 hybrid (weak to moderate ER+ and HER2+). The average Ki-67 index was lowest in luminal A (15.8%), intermediate for ERBB2 (27.8%) and highest for triple negative tumors (>50%). Multivariate logistic regression analyses found the following associations: ERBB2 tumors with apocrine differentiation (p=0.0031); Triple negative tumors with high Ki-67 index (p<0.0001) and CK5 positivity (p<0.0001); HER2 negative-low receptor positive tumors (luminal B) with increased lymph node involvement (p=0.0141). The immunohistologic criteria were validated on a different set of 359 cases treated with neoadjuvant chemotherapy, which showed a pathologic complete response predominantly in ERBB2 and triple negative tumors. Immunohistochemistry is a reliable surrogate tool to classify breast carcinoma according to the gene expression profile classification.
...
PMID:Prevalence, morphologic features and proliferation indices of breast carcinoma molecular classes using immunohistochemical surrogate markers. 1929 3

This study aims to evaluate large cell carcinomas (LCC) of the lung with a panel of immunohistochemical markers in an attempt to identify tumors belonging to other categories. We analyzed a tissue microarray platform of 101 LCC with a panel of 31 monoclonal antibodies. The tumors were 82 (81.3%) classic LCC, 7 (6.9%) neuroendocrine LCC, 6 (5.9%) lymphoepithelioma-like LCC, 3 (2.9%) basaloid LCC, 2 (2%) clear cell LCC, and 1 (1%) LCC with rhabdoid phenotype. Characteristic classic LCC immunophenotype was loss of staining with CK5/6, CK14 positive in most squamous cell carcinoma (SCC), lack of MOC 31 positive in most adenocarcinomas, and positive immunoreactivity to EGFR, PDGFR-alpha and c-kit. 27 of 82 classic LCC (32.9%) were re-classified as adenocarcinomas, because they coexpressed TTF-1, CK7, and CK19, and were negative for p63. 31 (37.8%) of 82 classic LCC were reclassified as poorly differentiated SCC, based on their immunoreactivity with 34betaE12, p63, thrombomodulin, and CD44v6. 16 (19.5%) of 82 classic LCC correspond to undifferentiated adenosquamous carcinomas, since they displayed conflicting immunostaining for markers of both SCC and adenocarcinomas. The use of 7 immunohistochemical markers, consisting of TTF-1, CK7, CK19, p63, 34betaE12, thrombomodulin, and CD44v6, markedly reduces dramatically to less than 10%, the number of classic LCC by readily identifying cases of poorly differentiated SCCs, adenosquamous carcinoma and adenocarcinomas.
...
PMID:Large cell carcinoma of the lung: an endangered species? 1944 77

The author reports a rare case of sarcomatoid carcinoma with an emphasis on immunohistochemical features. A 79-year-old man was admitted to our hospital because of hematuria. An endoscopy revealed a large polypoid tumor in the bladder, and urine cytology demonstrated malignant cells. A cystectomy was performed. The patient is now alive without metastasis 4 months after the operation. Grossly, a large polypoid tumor (5 x 6 x 5 cm) was present in the bladder. Microscopically, the tumor consisted of high-grade transitional cell carcinoma element (10% in area) and sarcomatoid element (90% in area). There was a gradual transition between the two. The tumor cells were invaded into peribladder tissue (pT3b). Immunohistochemically, the sarcomatoid element was positive for four types of pancytokeratins, high-molecular weight cytokeratin (CK), CK5/6, CK7, CK18, CK19, epithelial membrane antigen (EMA), vimentin, p53 protein, p63, Ki-67 (labeling = 92%), neuron-specific enolase (NSE), and platelet-derived growth factor receptor-alpha (PDGFRA). It was negative for CK14, CK20, melanosome, carcinoembryonic antigen (CEA), desmin, S100 protein, myoglobin, alpha-smooth muscle antigen (ASMA), CD34, chromogranin, synaptophysin, CD56, CD68, and KIT. The transitional cell carcinoma element showed similar immunoreactivity except for negative CK5/6, positive CK20, and negative vimentin. A molecular genetic analysis of KIT gene (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) gene with the use of PCR-direct sequencing showed no mutations. The present case is the first report of sarcomatoid carcinoma of the urinary bladder demonstrating extensive immunohistochemistry and mutational status of KIT and PDGFRA genes. The sarcomatoid carcinoma in the present case may be derived from sarcomatous differentiation of high-grade transitional cell carcinoma.
...
PMID:Sarcomatoid carcinoma of the urinary bladder: a case report with immunohistochemical and molecular genetic analysis. 1952 96

The author reports a very rare case of cutaneous metastasis of sarcomatoid carcinoma of the lung. The skin metastasis was an initial presentation. A 67-year-old man consulted our hospital because of left chest skin mass. An excisional biopsy was performed, and it showed proliferation of malignant sarcomatoid spindle and polygonal cells in the deep dermis and subcutis remote from the epidermis and appendages. Immunohistochemically, the tumor cells were positive for pancytokeratins, cytokeratin (CK) 7, CK 18, vimentin, p53, Ki-67 (95%) and PDGFRA. They were negative for high molecular weight CK, CK 5/6, CK 14, CK 19, CK 20, epithelial membrane antigen, TTF-1, CEA, desmin, S100 protein, alpha-smooth muscle actin, p63, CD34, surfactant apoprotein A, chromogranin, synaptophysin, neuron-specific enolase, CD68, CD56, D2-40, calretinin and KIT. A pathological diagnosis of metastatic sarcomatoid carcinoma probably originating from the lung was made. Then, the patient was admitted to our hospital, and imaging modalities including computed tomography (CT) and magnetic resonance imaging (MRI) revealed a tumor in the left lung. No other tumors were detected in the imaging techniques. Lung biopsy was planned, but the patient suddenly died; the cause of death was unclear. Autopsy was not performed. The present report suggests that sarcomatoid carcinoma of the lung should be considered in cutaneous metastatic lesions.
...
PMID:Sarcomatoid carcinoma of the lung presenting as a cutaneous metastasis. 1960 61

Breast cancers of basal phenotype have been identified by molecular profiling and are associated with a poor prognosis. This review describes the morphological characteristics of these tumors and focuses on their profiling using immunohistochemistry: absence of detectable hormone receptors and HER2, expression of basal cytokeratins (CK5/6, CK14), myoepithelial markers (p63, smooth muscle actin) and HER1. This phenotype may be encountered in all histological types of breast cancer and is further divided into three subtypes according to prognosis and protein profiling. Pure basal and basal/myoepithelial subtypes have a poor prognosis in contrast to the myoepithelial subtype.
...
PMID:[Basal-like breast cancer: a review]. 1961 22

The clinical, pathologic, and molecular features of pleomorphic lobular carcinoma in situ (PLCIS) and the relationship of PLCIS to classic LCIS (CLCIS) are poorly defined. In this study, we analyzed 31 cases of PLCIS (13 apocrine and 18 nonapocrine subtypes) and compared the clinical, pathologic, immunophenotypic, and genetic characteristics of these cases with those of 24 cases of CLCIS. Biomarker expression was examined using immunostaining for E-cadherin, gross cystic disease fluid protein-15, estrogen, progesterone, androgen receptor, human epidermal growth factor receptor2, CK5/6, and Ki67. Array-based comparative genomic hybridization to assess the genomic alterations was performed using microdissected formalin-fixed paraffin-embedded samples. Patients with PLCIS presented with mammographic abnormalities. Histologically, the tumor cells were dyshesive and showed pleomorphic nuclei, and there was often associated necrosis and microcalcifications. All lesions were E-cadherin negative. Compared with CLCIS, PLCIS showed significantly higher Ki67 index, lower estrogen receptor and progesterone receptor expression, and higher incidence of HER2 gene amplification. The majority of PLCIS and CLCIS demonstrated loss of 16q and gain of 1q. Apocrine PLCIS had significantly more genomic alterations than CLCIS and nonapocrine PLCIS. Although lack of E-cadherin expression and the 16q loss and 1q gain-array-based comparative genomic hybridization pattern support a relationship to CLCIS, PLCIS has clinical, mammographic, histologic, immunophenotypic, and genetic features that distinguish it from CLCIS. The histologic features, biomarker profile, and genomic instability observed in PLCIS suggest a more aggressive phenotype than CLCIS. However, clinical follow-up studies will be required to define the natural history and most appropriate management of these lesions.
...
PMID:Genetic and phenotypic characteristics of pleomorphic lobular carcinoma in situ of the breast. 1970 Oct 73

Gene expression profiling with breast carcinomas has allowed further classification of these tumors into 5 distinct subtypes (luminal A, luminal B, HER2-overexpression, basal-like, and normal-like) with unique clinical outcomes. Subsequent studies have shown that breast carcinomas can also be divided into 5 similar subgroups using immunohistochemical (IHC) analysis with a limited panel of molecular markers (including estrogen receptor, progesterone receptor, HER2, CK5/6, and epidermal growth factor receptor). These subgroups have distinguishing features closely associated with subtypes defined by gene expression profiling, including distinct clinical outcomes. This review aims to present the current data on molecular classification for breast carcinoma, and its clinical significance, with an emphasis on IHC-based studies and the pros and cons of these molecular classifications. We also propose a standardized IHC-based molecular classification, in the hope that it will promote more uniform large multicenter studies, and facilitate its clinical application.
...
PMID:Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? 1970 56

Approximately 10 - 15% of breast carcinomas (BCs) are known to be 'triple-negative (TN) receptor' (i.e., not expressing ER or PR and not exhibiting overexpression and/or gene amplification of HER2-neu). Triple-negative BCs comprise approximately 85% of all basal-type tumours. Classically, basal-like BCs have been characterised by low expression of ER, PR, and HER2 neu and high expression of CK5, CK14, caveolin-1, CAIX, p63, and EGFR (HER1), which reflects the mammary gland basal/myoepithelial cell component. Although there is no standard first-line chemotherapy regimen for metastatic TN BCs, anthracycline- and taxane-containing regimens are acceptable treatments. A large number of agents, including DNA-damaging agents, EGFR inhibitors, antiangiogenic agents and novel taxane formulations are currently being tested in clinical trials for first-line and pretreated patients. Limited experiences with platinum salts, poly(ADP-ribose) polymerase (PARP) inhibitors, cetuximab, bevacizumab and ixabepilone have been published in recent years and will be reported. Novel immunohistochemistry analysis for identification of basal like/TN phenotype are awaited to correctly select this population. The clinical trials investigating new agents have to be designed for a specific (and possibly large) subset of patients with BC. In the future, a gene array platform with greater sensitivity for distinguishing the various BC subtypes, as well as having the power to predict the molecular biology of the disease, will be an indispensible tool for treatment selection. Currently, treatment of TN BC is more empirical than evidence-based. The cornerstone of treatment is chemotherapy, but in the near future, novel target agents will emerge as possible partners.
...
PMID:Current data of targeted therapies for the treatment of triple-negative advanced breast cancer: empiricism or evidence-based? 1973 14

This is a study of 205 consecutive invasive breast carcinomas. The principal aim was to identify morphologic and immunohistochemical features of tumors that belong to the molecular class ERBB2. The invasive breast carcinomas were classified using semiquantitative immunohistochemical results for estrogen receptor (ER), progesterone receptor, (PR), and HER2 into following classes: Luminal A (strong ER+, HER2 negative), Luminal B (weak to moderate ER/PR+, HER2 negative), Triple Negative (TN; ER/PR negative, HER2 negative), ERBB2 (ER/PR negative, HER2 positive), Luminal A-HER2 Hybrid (strong ER+, HER2 positive), Luminal B-HER2 Hybrid (weak to moderate ER/PR+, HER2 positive). Of the 205 tumors, 113 (55%) were classified as Luminal A, 34 (17%) as Luminal B, 32 (15%) as TN, 8 (4%) as ERBB2, 10 (5%) as Luminal A-HER2 Hybrid, and 8 (4%) as Luminal B-HER2 Hybrid. Majority of the ERBB2 tumors were high grade as expected, with average Nottingham score of 8. Moderate lymphoid infiltrate (constituting 25% to 50% of the tumor) was seen in 5 of 8 (63%) cases and necrosis in 3 of 8 (38%) cases. The most striking morphologic feature associated with ERBB2 tumors was the presence of apocrine differentiation seen in 7 of 8 (88%) cases. CK5 immunoreactivity was seen in 5 of 8 cases (63%). Epidermal growth factor receptor staining with 2+ or 3+ score was also seen in 5 cases (63%). Due to low prevalence of ERBB2 tumors, additional data set of 191 cases enriched in ERBB2 and TN tumors was used for confirmation of morphologic findings. We conclude that tumors with apocrine differentiation are most often of ERBB2 type. ERBB2 tumors demonstrate some features classically ascribed to TN basal-like tumors. Epidermal growth factor receptor overexpression in ERBB2 tumors may have additional predictive value.
...
PMID:Breast cancer molecular class ERBB2: preponderance of tumors with apocrine differentiation and expression of basal phenotype markers CK5, CK5/6, and EGFR. 1980 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---