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)

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.
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PMID:Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications. 1721 55

We have evaluated HER2/neu expression in 1,355 breast cancer patients recruited at the Breast Cancer Registry in Palermo between January 1999 and December 2004. In this retrospective study, HER2/neu expression was related to clinicopathologic features of the disease, including tumor size, nodal and menopausal status, estrogen and progesterone receptors. Statistical analysis on all 1,355 patients showed a significant correlation between HER2/neu and nodal status (P < 0.001), and a significant association between HER2/neu overexpression and estrogen and progesterone receptors status (P < 0.001). In 194 patients without metastasis, with an average follow-up > or =5 years, only HER2/neu 3+ and histopathologic grading G3 were significantly associated with overall survival.
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PMID:HER2/neu expression in relation to clinicopathologic features of breast cancer patients. 1726 64

The HER receptors are of therapeutic and prognostic significance in breast cancer, and their function is modulated by cytoplasmic tyrosine kinases like PTK6 (brk). We performed a retrospective study on archival breast cancer samples from patients with long follow-up and compared the protein expression between individual HERs and between HERs and the PTK6. Univariate and multivariate analyses were used to study the prognostic value of parameters. Metastases-free survival of patients for longer than 240 months was inversely associated (P< or =0.05) with nodal status, tumour size, and oestrogen receptor status, but was also directly associated with high protein expression levels of HER4 and PTK6 in Kaplan-Meier analysis. In multivariate analysis for metastases-free survival of >240 months, the stepwise selected parameters were tumour size (relative risk 3.1), PTK6 expression (0.4), and number of positive lymph nodes (1.2). Furthermore, we demonstrated a timedependence of the prognostic value attributed to the parameters. The HER receptors (HER2,4), but not PTK6, were independent prognostic markers for metastases-free survival at 60 months, whereas at 240 months PTK6 is the strongest prognostic marker. We demonstrate that PTK6 is a prognostic marker of metastases-free survival in breast cancer, and is independent of the classical morphological and molecular markers of lymph node involvement, tumour size, and HER2 status.
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PMID:PTK (protein tyrosine kinase)-6 and HER2 and 4, but not HER1 and 3 predict long-term survival in breast carcinomas. 1729 91

Despite new diagnostic and therapeutic strategies (combined radiochemotherapy, EGFR antibody Cetuximab), the prognosis of head and neck squamous cell carcinoma (HNSCC) is still poor and more information regarding prognosis is essential to establish earlier and better treatment options. To elucidate the role of DNA ploidy and cellular proliferation, resected tumors of 48 patients with primary or recurrent HNSCC were analyzed by flow cytometry and in vitro-5-bromodeoxyuridine incorporation (BrdU). The results were compared with histopathological findings such as tumor size, lymph node involvement and tumor differentiation. To assess the influence of intratumoral heterogeneity of these biological parameters, multiple biopsies (>3) were analyzed by flow cytometry and BrdU-incorporation in 12 larger (>4 cm diameter) tumors. BrdU-labeling index (LI%) was significantly higher in aneuploid HNSCC and correlated significantly with poor histologic differentiation of the analyzed tumor tissues (P<0.001). Furthermore, a trend for higher LI% in nodal positive tumors was observed. Aneuploid HNSCC showed significantly more often tissue dedifferentiation (P=0.049) and in most cases an advanced tumor stage, especially in tumors with biclonal cell lines. Lymph node involvement was also seen more often in aneuploid and undifferentiated tumors. As in aneuploid tumors recurrent HNSCC showed in most cases a higher LI% and poor tissue differentiation, but as a result of the small collection of samples there was no correlation between aneuploidy and tumor recurrence. To proof the robustness of the acquired data and to estimate the influence of intratumoral heterogeneity to ploidy and LI% multiple biopsies were analyzed in larger tumors. Using a specific statistical algorithm a secure estimation of ploidy and LI% was possible by a single biopsy in these tumors. These findings indicate aneuploidy and proliferative activity as important findings for malignant progression in HNSCC. An estimation of these biological parameters may be useful for identification of patients with high risk for lymph node involvement or tumor recurrence and pre-treatment can be performed by a single biopsy. As a conclusion, these patients may benefit from more aggressive treatment.
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PMID:DNA ploidy, proliferative capacity and intratumoral heterogeneity in primary and recurrent head and neck squamous cell carcinomas (HNSCC)--potential implications for clinical management and treatment decisions. 1735 Mar 26

Medullary thyroid carcinoma (MTC) is a rare malignancy of the thyroid C cells. It occurs in hereditary (25% of cases) and sporadic (75%) forms. Sporadic MTCs frequently metastasize to cervical lymph nodes. Thorough surgical extirpation of the primary tumor and nodal metastases by compartment-oriented resection has been the mainstay of treatment (level IV evidence). Surgical resection of residual and recurrent disease is effective in reducing calcitonin levels and controlling complications of central neck disease (level IV evidence). Radioactive iodine, external beam radiation therapy, and conventional chemotherapy have not been effective. Newer systemic treatments, with agents that target abnormal RET proteins hold promise and are being tested in clinical trials for patients with metastatic disease.
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PMID:Evidence-based approach to the management of sporadic medullary thyroid carcinoma. 1742 1

Medullary thyroid carcinoma (MTC) is developed from thyroid C cells that secrete calcitonin (CT). MTC represents 5-10% of thyroid cancers with a 1-2% incidence in nodular thyroid diseases. Diagnosis is usually made by a solitary nodule often associated to nodal metastasis and confirmed by a high basal CT level which represents its biological marker. MTC may present as a sporadic form and in about 30% of case as a familial form as a part of multiple endocrine neoplasia syndrome, an hereditary dominant inherited disease related to germline mutation of the proto-oncogene RET. Both biological (CT) and genetic (RET) markers allows the optimal diagnosis and treatment of MTC; the former allows screening and early diagnosis of MTC by routinely CT measurements in nodular thyroid diseases that make the adequate and complete surgery required to be performed. The former leads to diagnose familial MTC and to identify at risk subjects in whom early or prophylactic surgery may be performed. Treatment of MTC is based on the complete surgical resection: total thyroidectomy associated to central and laterocervical nodal dissection. For locally advanced or metastatic MTC, complete cervical surgery is required and needs to be associated to other systemic treatments: as chemotherapy is not very efficient, radioimmunotherapy and RET target gene therapy (mainly tyrosine kinase inhibitors) appears as possible valuable therapeutic options for the future. Prognosis of MTC is mainly related to both the stage of the disease and the extend of the initial surgery. Ten-year survival is about 80% when the patients are not surgically cured and reaches 95% when the biological marker CT is normalized after surgery.
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PMID:[Medullary thyroid carcinoma]. 1757 72

High expression of the cancer-testis antigen CT7, also referred to as MAGE-C1, has been recently described in a variety of malignant tumors, including breast carcinoma. To our knowledge, no data concerning the prognostic utility of CT7 expression in breast cancer are available. In this retrospective study, we evaluated the relationship between CT7 immunoreactivity and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 124 women with invasive breast cancer. A positive CT7 status, defined as immunoreactivity in more than 50% of tumor cells, was found in 18% of cases and correlated significantly with high tumor grade (p=0.004), but with no other clinicopathological parameter. In a univariate analysis, CT7 status showed an association with RFS by trend (p=0.107; relative risk [RR]: 1.85) and a significant association with MFS (p=0.043; RR: 2.02). In a multivariate analysis, tumor grade, stage, nodal status, angioinvasion, HER2 expression as well as estrogen and progesterone receptor expression were identified as significant independent prognostic factors of RFS and/or MFS. In this respect, CT7 expression showed a weak, statistically not significant trend towards an independent prognostic relevance concerning prediction of MFS (p=0.147; RR: 1.95). Our data suggest that estimation of CT7 immunoreactivity is of limited prognostic usefulness in breast cancer. It may provide additional information concerning assessment of MFS in selected cases.
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PMID:Expression of cancer-testis antigen CT7 (MAGE-C1) in breast cancer: an immunohistochemical study with emphasis on prognostic utility. 1760 69

The epidermal growth factor receptor (EGFR) and the estrogen receptor (ER) modulator Amplified In Breast cancer-1 (AIB1) have been reported to be of importance for the prognosis of breast cancer patients. We have analyzed AIB1 and EGFR by immunohistochemistry in primary breast cancers (n = 297) arranged in a tissue microarray in order to predict outcome after adjuvant endocrine therapy with tamoxifen for two years. High expression of AIB1 was associated with DNA-nondiploidy, high S-phase fraction, HER2 amplification, and short term (<or=2 years) distant disease-free survival (DDFS), independent of ER status. High expression of EGFR was strongly associated to ER negativity and also correlated with progesterone receptor negativity, high S-phase fraction, and inversely correlated with nodal metastases. In univariate analysis, high EGFR was associated with shorter DDFS (hazard ratio 2.1; P = 0.017), and reached borderline significance in a multivariate analysis, adjusting for ER, menopausal and lymph node status, tumor size, and HER2 (P = 0.057). In conclusion, both AIB1 and EGFR were associated to DDFS for breast cancer patients treated with two years of adjuvant tamoxifen; AIB1 with the development of early distant recurrences, indicating association between high AIB1 and resistance to tamoxifen during treatment, and EGFR with distant recurrences up to a follow up of five years.
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PMID:Epidermal growth factor receptor (EGFR) and the estrogen receptor modulator amplified in breast cancer (AIB1) for predicting clinical outcome after adjuvant tamoxifen in breast cancer. 1763 98

In an attempt to find genes that may be of importance in malignant progression of papillary thyroid carcinoma (PTC) in the Middle East, which therefore can be targeted in cancer therapy, we screened and validated the global gene expression in PTC using cDNA expression arrays and immunohistochemistry (IHC) on tumour tissue microarrays. Twenty-nine PTC tissue specimens were compared with seven non-cancerous thyroid specimens by use of cDNA microarray. Results for selected genes were confirmed by quantitative real-time PCR. Protein expression of selected genes was further studied using a tissue microarray consisting of 536 PTCs and compared with histologically non-cancerous tissue samples. One hundred and ninety-six genes were overexpressed in PTC tissues relative to non-cancerous thyroid tissues. The genes that were up-regulated in PTC were involved in cell cycle regulation, cell signaling, and oncogenesis. Among these genes, c-MET was identified by immunohistochemical methods as a protein that is overexpressed in 37% of PTCs and was significantly associated with more aggressive behaviour, eg higher stage, nodal involvement, and tall cell variant (p value = 0.01, 0.01 and 0.04, respectively). In this study, 55% of the PTC cases expressed activated AKT (P-AKT), which suggests that activated AKT may play an important role in PTC tumourigenesis. The fact that most of the PTC cases that had activated AKT showed overexpression of c-MET (p = 0.027) leads us to hypothesize that c-MET may be an alternative mechanism of AKT activation in Middle Eastern PTCs. Finally, our data suggest that c-MET dysregulation is associated with aggressive behaviour and may serve as a molecular biomarker and potential therapeutic target in this disease.
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PMID:Genome-wide expression analysis of Middle Eastern papillary thyroid cancer reveals c-MET as a novel target for cancer therapy. 1770 98

Columnar cell lesions (CCLs) of the breast are reported with increasing frequency. However, the significance of these lesions and the treatment approach to these lesions are still unknown. The aim of the present study was to evaluate c-KIT expression in CCLs accompanying benign and malignant breast diseases. A total of 65 patients (18 benign breast diseases, 8 ductal carcinomas in situ (DCI), and 39 invasive carcinomas) were included in the study. c-KIT was strongly expressed in normal breast epithelium (staining intensity; SI: 3 +/- 0.0), whereas a heterogeneous and cytoplasmic staining pattern was observed in CCLs accompanying both benign and malignant diseases. c-KIT expression was decreased, with increasing atypia in CCLs (SI in CCLs with/without atypia; 1.45 +/- 0.52/no case, 1.25 +/- 0.50/1.38 +/- 0.52, 0.77 +/- 0.73/1.21 +/- 0.42 accompanying benign breast disease, DCI and invasive carcinoma, respectively). c-KIT expression was detected in 10.4% of invasive carcinomas. No significant association between c-KIT expression and the histologic grade and nodal status of tumor was noted. As there is a reduction in c-KIT expression with malignant transformation of breast epithelium, c-KIT is believed to play a role in breast carcinogenesis. Furthermore, similar c-KIT expression patterns in CCLs accompanying malignant breast diseases suggest that at least some CCLs could reflect a premalignant status of breast carcinoma. However, the significance of c-KIT expression in CCLs and its relationship to breast carcinogenesis should be evaluated in follow up studies investigating larger series.
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PMID:c-KIT expression in columnar cell lesions of the breast accompanied by benign and malignant breast diseases. 1793 92


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