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

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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)

Historically, the selection of adjuvant systemic therapy in early breast cancer has relied on risk assessment embodied by the TNM classification. Since the 2005 International St. Gallen Consensus, treatment selection now involves firstly identifying critical targets and then using risk to assess the trade-off between anticipated toxicity and efficacy. This evolution in treatment strategies began with the identification of the estrogen receptor, and culminated with the HER2 receptor, with recent astounding success in several adjuvant trials. Newer technologies including gene expression profiles and micrometastases tracking bear exciting potential in refining the treatment strategies further. Alongside the progress in developing agents that target different molecules across the whole breast cancer population, these newer technologies aim to tailor adjuvant treatment further by identifying breast cancer subgroups that may benefit most from being targeted with specific therapy, by defining molecular subtypes, recognizing chemo-sensitivity and resistance, identifying at-risk gene signatures, and by detecting stem cells capable of generating metastases. This paper will review this evolution of treatment strategies, from the lessons learnt from the past, to the exciting promise of tailored therapy of the future.
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PMID:The evolution of treatment strategies: aiming at the target. 1776 40

An accurate investigation of the HER2 proto-oncogene is extremely important for the therapy and prognostication of breast cancer. Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are standard methods for this purpose. The aim of this study was to detect the expression and amplification of HER2 in paraffin-embedded samples of breast cancer tissue and to investigate the relationship between HER2 amplification and various clinicopathological parameters in advanced breast cancers. We used FISH to examine the HER2 gene amplification and IHC to examine the expression of HER2 protein, estrogen receptor (ER) and progesterone receptor (PR) in 62 advanced breast cancers. HER2 gene amplification was detected by FISH in 12 breast cancers (19%) and HER2 protein expression with a score of 3+ was detected by IHC in 11 (17%). There was a significant correlation between the HER2 gene amplification and HER2 protein overexpression in breast cancers (P<0.0001). However, some mismatching was evident: 3 cases, negative for the HER2 gene, showed a HER2 protein expression score of 3+ and 2 cases, positive for HER2 gene amplification, had HER2 protein expression scores of 0 and 1+ (negative), respectively. ER and PR were expressed in 41 (66%) and 46 (74%) cancers, respectively. No correlation was observed between the HER2 gene amplification and any of the clinicopathological parameters examined, including age, histopathological type, TNM stage, tumor size, lymph node status, relapse and expression of PR. We observed three patterns among the 6 deceased cases: i) triple negativity for HER2, ER and PR, ii) positivity for HER2 gene amplification with a mismatching HER2 protein expression, and iii) positivity for the HER2 gene amplification with a matching HER2 protein expression score of 2+ or 3+. The triple negative cases and HER2 gene amplification positive cases with a mismatching HER2 protein expression had a poor outcome. These results suggest that in breast cancer, the detection of HER2 gene amplification by FISH is desirable compared with the HER2 protein expression determined by IHC. Moreover, triple negativity for HER2, ER and PR is a potentially very important prognostic marker.
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PMID:Prognostic utility of fluorescence in situ hybridization for determining HER2 gene amplification in breast cancer. 1828 97

Cortactin, fascin-1 and EGFR are recognized as important factors in tumor progression. We tested the hypothesis that cortactin, fascin-1 and EGFR expression correlates with clinicopathological parameters of the four most common ovarian surface epithelial carcinomas--serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid adenocarcinoma, and clear cell carcinoma. Immunohistochemical analysis of cortactin, fascin-1 and EGFR was performed using tissue microarrays of 172 specimens comprising 69 serous cystadenocarcinomas, 44 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas and 14 clear cell carcinomas. All ovarian carcinomas showed significant expression of cortactin, fascin-1 and EGFR in staining intensity, tumor percentages and immunostaining scores. In addition, higher immunostaining scores of fascin-1 correlated with more advanced cancer stages (TNM), poorer histological differentiation and poorer survival rate of mucinous cystadenocarcinoma. Similarly, higher immunostaining scores of cortactin correlated with T stages and histological differentiation of serous cystadenocarcinoma. The immunostaining scores of EGFR did not correlate with TNM stages, tumor differentiation or prognosis in the four ovarian surface epithelial carcinomas. Our findings suggest that cortactin and fascin-1 may serve as good biomarkers in evaluating aggressiveness of ovarian serous and mucinous cystadenocarcinoma. And the pharmacological inhibitors of fascin-1 activity may slow down tumor progression and prolong survival time in patients with mucinous cystadenocarcinoma.
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PMID:Association of cortactin, fascin-1 and epidermal growth factor receptor (EGFR) expression in ovarian carcinomas: correlation with clinicopathological parameters. 1877 88

Breast carcinoma is the most common malignant tumour and the main cause of carcinoma death in women. There has been a sharp increase in the detection of breast carcinoma, although mortality is still unvaried. In the last ten years the incidence of breast cancer measuring less than 1 cm, corresponding to pT1a, pT1b in TNM stadiation, has greatly increased. The present study describes the biologic characterisation of small breast carcinomas. The Nottingham/Tenovus Primary Breast Cancer Study stated that tumour size is a significant, independent factor for breast cancer prognosis. Cases were selected among formalin-fixed, paraffin-embedded tissues from 360 ductal breast cancers. In one-half of cases, the tumour was less than 1 cm in diameter, pT1a- pT1b; in the other half the tumour size was greater than 1 cm, but less than 2 cm, pT1c. Histological grading was assessed with the Scarff-Bloom-Richardson method, without Nottingham grade. Immunohistochemical determinations for ER, PgR, Ki-67, Her-2/Neu, CD34, p53, EGFR were done with an automated method. From the above analyses, it was demonstrated that the tumour size is indeed an important prognostic factor, particularly in cases without lymph node metastasis (N0). In particular, we observed significant differences between pT1a-b and pT1c cases, confirming that tumour size is an important criterion for prognostic valuation in ductal breast cancer without lymph node metastasis.
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PMID:[Breast cancer less than 1 cm: bio-morphologic characterization with ER, PgR, Ki67, Her-2/Neu, MDV, MAGS, p53, EGF-R]. 1884 18

A new classification based on gene expression profiling or immunohistochemical (IHC) characteristics may replace current histopathological classifications and predict better clinical outcomes. We used IHC markers to classify incident cases ascertained by the Palermo Breast Cancer Registry (2002-2004) into four subtypes: luminal-A (ER+ or PgR+ and HER2/neu-); luminal-B (ER+ or PgR+, HER2/neu+); basal-like (ER-, PgR-, HER2/neu-); and HER2+/ER- (HER2/neu+, ER-, PgR-). We evaluated HER2/neu, ER and PgR in 1300/1985 (65%) cases. The most common IHC-subtype was luminal-A (68%), whereas luminal-B, basal-like, and HER2+/ER- accounted for 14%, 13%, and 5%, respectively. IHC-subtypes were not associated with tumor size, geographic location within the province, or menopause, but differed by NPI (P < 0.0001), grading (P < 0.0001), lymph-node involvement (P= 0.04), metastases (P= 0.04), and TNM stage (P= 0.04). Endocrine therapy was administered to 81% of 519 postmenopausal, luminal-A, and luminal-B cases and to 32% of 114 postmenopausal, basal-like, and HER2+/ER- cases.
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PMID:Application of a new classification to a breast tumor series from a population-based cancer registry: demographic, clinical, and prognostic features of incident cases, Palermo Province, 2002-2004 . 1925 Feb 7

An impressive number of publications refer to prognostic and predictive factors in lung cancer. TNM classification and performance status significantly influence the choice of treatment and strongly predict patients' survival. Depending on the population studied (small cell or non-small cell cancer, operable or not) other independent factors improve the prediction of prognosis; they are clinical, biological, radiological or molecular and pertain to the tumor or the patient. Molecular targeted therapies development has renewed the interest towards predictive factors. New strategies are developed to explore individual response to treatment such as EGFR tyrosine-kinase inhibitors, without success for anti-angiogenic treatments. Conventional cytotoxic agents may also be customized with predictive factors (i.e. ERCC1 or RRM1). Large multicenter studies are needed to validate new independent prognostic factors and increase our current knowledge aiming at separating patients who will really benefit from therapies of those who will only experience the side effects.
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PMID:[Prognostic and predictive factors in lung cancer]. 1935 14

There is no optimal established therapy for treating advanced or recurrent adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC), and it remains unclear whether chemotherapy achieves therapeutic results comparable to those seen in the more common non-small lung carcinoma subtypes. In order to improve the decisions made during the treatment of advanced ADC-BAC, we attempted to better characterize the mucinous and non-mucinous ADC-BAC subtypes. Fifty pathological samples were obtained from 62 patients included in a multicenter prospective phase II trial (IFCT0401) conducted to evaluate gefitinib as a first-line therapy for non-resectable ADC-BAC. These samples were centrally reviewed and re-classified as non-mucinous (n=25) or mucinous (n=25) subtypes. We demonstrated that demographic data, clinical characteristics and stage at presentation (extrathoracic versus lung metastasis, as well as TNM staging) did not distinguish between the two subtypes. In contrast, three biological markers (PAS staining, TTF-1 expression and EGFR genomic gain combined with mutation analysis) enabled us to independently segregate all but 2 of the 50 patients into the mucinous and non-mucinous ADC-BAC subtypes. Finally, only mucinous tumors appeared to be resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Additional prospective studies are required to better approach therapeutic strategy in mucinous tumors, which are a distinct entity from non-mucinous tumors.
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PMID:Non-mucinous and mucinous subtypes of adenocarcinoma with bronchioloalveolar carcinoma features differ by biomarker expression and in the response to gefitinib. 1958 Oct 16

Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and hormonal therapies. Previous studies have shown over-expression of EGFR is associated with high grade tumors and a worse prognosis. Recent studies suggest anticancer therapies targeting the EGFR pathway have shown promising results in clinical trials of RCC patients. Therefore, characterization of the level and localization of EGFR expression in RCC is important for target-dependent therapy. In this study, we investigated the clinical significance of cellular localization of EGFR in human normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63 patients were obtained for characterization of EGFR expression. EGFR protein expression was assessed by immunohistochemistry on a scale from 0 to 300 (percentage of positive cells x staining intensity) and Western blotting. EGFR membranous staining was significantly stronger in RCC tumors than in normal tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly higher in normal than in tumor tissues (P < 0.001). The levels of membranous or cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor grade, TNM stage or overall survival (P > 0.05). These results showed abundant expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR in normal tissues. EGFR expression in RCC was mostly located in the cell membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in cytoplasm. Our results suggest different locations of EGFR expression may be associated with human renal tumorigenesis.
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PMID:Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma. 1974 98

The prognostic factors of young breast cancer patients (BCPs) are still controversial. This study is aimed at evaluating the prognosis of young BCPs by characteristics and treatment response. We analysed the data on 2,593 operable BCPs age <or=50 years who were treated in the Cancer Hospital of Fudan University, Shanghai, China between 1990 and 2004. The overall survival and recurrence/metastasis-free survival were compared. In the study, 782 patients (30.2%) were <or=40 years, and 1,811 (69.8%) were 41-50 years old at their primary diagnosis. BCPs <or=40 years presented more unfavourable features than the 41-50 years BCPs (P < 0.05). They were more likely to experience death (P < 0.001) and recurrence/metastasis events (P < 0.001) even when they underwent the same adjuvant therapy in parallel with their counterparts (P < 0.05). In a multivariate analysis, age was an independent predictive factor for RFS (HR = 0.26, 95% CI = 0.44-0.89, P = 0.009) but not for OS (P > 0.05). Higher TNM stage and chemotherapy, but not HER2/neu over-expression, were predictive factors for young Chinese BCPs. The characteristics of breast cancer are more aggressive in young Chinese BCPs. Their prognostic factors are obviously different from those of the elder group. Current therapy was not as effective for them.
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PMID:Unfavourable clinicopathologic features and low response rate to systemic adjuvant therapy: results with regard to poor survival in young Chinese breast cancer patients. 1976 32

Breast cancer associated with BRCA1 and BRCA2 gene mutations differs from non-BRCA tumors in several respects. We determined whether there was any difference in CCND1 (11q13) and ZNF217 (20q13) gene amplification with respect to BRCA status. Of 40 breast cancer samples examined, 15 and 9 were from BRCA1 and BRCA2 mutation carriers, respectively, and 16 from patients without mutation. Fluorescence in situ hybridization showed that eight tumors exhibited CCND1 amplification (20%; 3 BRCA1, 3 BRCA2, 2 non-BRCA). ZNF217 amplification was observed in three of 38 cases (8%; 2 BRCA1, 1 non-BRCA). There was no significant difference in CCND1 and ZNF217 amplification between BRCA1, BRCA2 and non-BRCA tumors. CCND1 amplification was associated with decreased disease-free (P = 0.045) and overall survival (P = 0.015). BRCA1 tumors with CCND1 amplification were estrogen receptor negative, in contrast to CCND1 amplified BRCA2 and non-BRCA tumors, suggesting that concurrent CCND1 amplification and estrogen and progesterone receptor negativity may predict germline BRCA1 gene mutation. All ZNF217 amplified tumors were of the medullary histological type (P = 0.002). There was no statistical correlation between CCND1 and ZNF217 amplification and estrogen receptor, progesterone receptor, and ERBB2 expression and TNM classification. CCND1 amplification did not correlate with EGFR expression.
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PMID:CCND1 and ZNF217 gene amplification is equally frequent in BRCA1 and BRCA2 associated and non-BRCA breast cancer. 2042 23


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