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)

Women with germ-line mutations of the BRCA1 tumor suppressor gene are highly susceptible to breast and ovarian cancer. The protein product of BRCA1 is involved in a broad spectrum of biological processes and interacts with many diverse proteins. One of these, BARD1, associates with BRCA1 to form a heterodimeric complex that is enzymatically active as an ubiquitin E3 ligase. Although the BRCA1/BARD1 heterodimer has been implicated in several aspects of BRCA1 function, its role in tumor suppression has not been evaluated. To address this question, we generated mouse strains carrying conditional alleles of either Bard1 or Brca1 and used Cre recombination to inactivate these genes in mammary epithelial cells. Significantly, the conditional Bard1- and Brca1-mutant mice developed breast carcinomas that are indistinguishable from each other (and from those of double conditional Bard1/Brca1-mutant animals) with respect to their frequency, latency, histopathology, and cytogenetic features. Reminiscent of the basal-like breast carcinomas seen in human BRCA1 mutation carriers, these tumors are "triple negative" for estrogen and progesterone receptor expression and HER2/neu amplification. They also express basal cytokeratins CK5 and CK14, have an elevated frequency of p53 lesions, and display high levels of chromosomal instability. The remarkable similarities between the mammary carcinomas of Bard1-, Brca1-, and Bard1/Brca1-mutant mice indicate that the tumor suppressor activities of both genes are mediated through the BRCA1/BARD1 heterodimer.
...
PMID:The basal-like mammary carcinomas induced by Brca1 or Bard1 inactivation implicate the BRCA1/BARD1 heterodimer in tumor suppression. 1844 92

Pure invasive micropapillary carcinoma (MPC) is a special histological type that accounts for 0.7-3% of all breast cancers. MPC has a distinctive growth pattern and a more aggressive clinical behaviour than invasive ductal carcinomas of no special type (IDC-NSTs). To define the molecular characteristics of MPCs, we profiled a series of 12 MPCs and 24 grade and oestrogen receptor (ER)-matched IDC-NSTs using high-resolution microarray comparative genomic hybridization (aCGH). In addition, we generated a tissue microarray containing a series of 24 MPCs and performed immunohistochemical analysis with ER, PR, Ki-67, HER2, CK5/6, CK14, CK17, EGFR, topoisomerase-IIalpha, cyclin D1, caveolin-1, E-cadherin, and beta-catenin antibodies. In situ hybridization probes were employed to evaluate the prevalence of amplification of HER2, TOP2A, EGFR, CCND1, MYC, ESR1, and FGFR1 genes. aCGH analysis demonstrated that MPCs significantly differed from IDC-NSTs at the genomic level. Gains of 1q, 2q, 4p, 6p, 6q23.2-q27, 7p, 7q, 8p, 8q, 9p, 10p, 11q, 12p, 12q, 16p, 17p, 17q, 19p, 20p, 20q, and 21q, and losses of 1p, 2p, 6q11.1-q16.3, 6q21-q22.1, 9p, 11p, 15q, and 19q were more prevalent in MPCs. High-level gains/amplifications of 8p12-p11, 8q12, 8q13, 8q21, 8q23, 8q24, 17q21, 17q23, and 20q13 were significantly associated with MPCs. A comparison between 24 MPCs and a series of 48 grade and ER-matched IDC-NSTs revealed that high cyclin D1 expression, high proliferation rates, and MYC (8q24) amplification were significantly associated with MPCs. Our results demonstrate that MPCs have distinct histological features and molecular genetic profiles supporting the contention that they constitute a distinct pathological entity.
...
PMID:Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast. 1848 83

Previous studies have suggested that breast cancer in young women has more aggressive biological features and poorer prognosis. However, the role of biological markers in these patients is not well understood. We aimed to learn more about this disease in a cohort of 125 young women from Singapore, Japan and Hong Kong, aged 35 years or less, with invasive breast cancer by evaluating the expression of vimentin and the basal cytokeratins CK14, CK5/6 and 34 beta E12. Both standard paraffin sections and tissue microarrays were used in the immunohistochemical evaluation of expression patterns of these four biological markers. CK5/6, CK14, vimentin and 34 beta E12, in increasing order of proportion, were detected in invasive carcinomas. Basal cytokeratins and vimentin showed significant inverse relationship with estrogen and progesterone receptor status while CK14 expression was found to be directly associated with c-erbB2 status. Basal cytokeratins and vimentin immunoreactivities were directly associated with CD117 and EGFR expression. Vimentin and 34 beta E12 immunopositivity correlated with tumor size, while vimentin was associated with higher histological grade. Our findings are in concert with reports that expression of basal cytokeratins and vimentin is correlated with adverse pathological parameters.
...
PMID:Expression of basal keratins and vimentin in breast cancers of young women correlates with adverse pathologic parameters. 1853 55

The basal-like phenotype (BLP) subtype of breast carcinoma has been identified as 1 of 5 tumor subtypes first revealed by microarray profiling. This phenotype tends to be more aggressive, is more often associated with BRCA1 mutations, and carries a poor prognosis. Few studies have morphologically characterized BLP on resected breast specimens (RS), and no studies have evaluated these diagnostic parameters in core needle biopsies (CNB) of breast. We identified a group of 35 RS that demonstrated BLP by morphology and/or immunophenotype based on the criteria used in the literature. Retrospectively, we reviewed the CNB of these RS for the following morphologic features: growth pattern, nuclear grade, mitotic rate, presence of ductal carcinoma in situ, necrosis, and lymphocytic response. Of these histologic features, solid growth pattern [88.6% (31/35)] with nuclear grade 3 [100% (35/35)], marked lymphocytic infiltrate [74.3% (26/35)], and absence or <5% of ductal carcinoma in situ [91.4% (32/35)] were seen most consistently in all the CNB. Geographic necrosis was seen in almost half of the cases [48.6% (17/35)]. Lymphovascular invasion and squamoid differentiation were limited to a small number of cases. On the basis of our results, we propose using certain morphologic features (solid growth pattern, high nuclear grade, presence of marked lymphocytic infiltrate, and geographic necrosis) in recognizing BLP on CNB. Triple negativity of estrogen receptor, progesterone receptor, and HER2/neu combined with positive BLP immunohistochemical markers such as the cytokeratins (CK): CK17, CK14, CK5/6, and epidermal growth factor receptor, help to further confirm the diagnosis.
...
PMID:Evaluation of morphologic features to identify "basal-like phenotype" on core needle biopsies of breast. 1854 31

The aim of present study is to explore the immunohistochemical profiles of brain metastases from breast cancer. We retrospectively performed immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2/neu), and cytokeratin (CK) 5/6 in 29 patients with resected tumor specimens of brain metastases. Immunohistochemical staining for ER, PgR and HER2/neu was performed in 24 patients with primary tumors. The positive frequency of immunohistochemical profiles of ER, PgR, HER2/neu, and CK5/6, in the brain metastases were 13.8%, 6.9%, 37.9%, and 24.1%, respectively. The immunohistochemical profiles including ER, PgR, and HER2/neu of the primary tumor and the brain metastasis differed in seven patients (29.2%, N = 7/24). Interestingly, the biological characteristics of brain metastasis sometimes changed which were represented by immunohistochemical staining. Therefore, the changes in the biological features of breast cancer should be taken into account when developing treatment strategies, including new molecular-targeted drugs, for brain metastases.
...
PMID:Immunohistochemical profiles of brain metastases from breast cancer. 1864 8

Spindle cell lesions of the urinary bladder are uncommon, but when encountered in clinical practice, pose a difficult diagnostic challenge as the differential diagnostic considerations are vast. Pseudosarcomatous processes significantly overlap with malignant tumors (sarcomatoid urothelial carcinoma and leiomyosarcoma) in their morphology and published immunohistochemical profile [pancytokeratin pan (CK), smooth muscle actin (SMA), and desmin]. p63 has been studied rarely and CK 5/6 and CK 34betaE12 have not been analyzed in the bladder in this diagnostic context. In the current study, 45 typical examples of spindle cell lesions [10 pseudosarcomatous myofibroblastic proliferations (PMP), 22 sarcomatoid urothelial carcinomas, and 13 smooth muscle tumors] of the urinary bladder were immunostained with a panel containing broad spectrum anticytokeratin antibodies (OSCAR or AE1/AE3), as well as antibodies to CK 34betaE12, CK 5/6, p63, SMA, and anaplastic lymphoma kinase (ALK). The immunoreactivity was as follows: PMP-CK (OSCAR) 7/10 (70%), CK (AE1/AE3) 7/9 (78%), CK 34betaE12 0/10 (0%), CK 5/6 0/9 (0%), p63 0/9 (0%), SMA 10/10 (100%), ALK 2/10 (20%); sarcomatoid urothelial carcinoma-CK (OSCAR) 15/22 (68%), CK (AE1/AE3) 14/20 (70%), CK 34betaE12 5/20 (25%), CK5/6 6/22 (27%), p63 11/22 (50%), SMA 16/22 (73%), ALK 0/22 (0%); and smooth muscle tumors-CK (OSCAR) 7/13 (54%), CK (AE1/AE3) 7/12 (58%), CK 34betaE12 0/12 (0%), CK 5/6 0/12 (0%), p63 3/13 (23%), SMA 11/13 (85%), ALK 0/13 (0%). Positivity for keratin was typically focal to moderate in smooth muscle tumors and more commonly moderate to diffuse in sarcomatoid carcinomas and PMP. Our data indicate that there is significant immunohistochemical overlap between the different spindle cell lesions, each of which has unique clinicopathologic, prognostic, and therapeutic ramifications. Within the context of morphology, an immunohistochemical panel composed of broad-spectrum antibodies to cytokeratin as well as antibodies to SMA, ALK, p63, and CK 5/6 will be a useful diagnostic adjunct: a combination of pankeratin, SMA, and ALK positivity favors PMP; expression of several cytokeratin and especially CK 34betaE12 and CK 5/6 with p63 favors sarcomatoid carcinoma and SMA positivity with overall absence of other markers favors leiomyosarcoma.
...
PMID:Utility of a comprehensive immunohistochemical panel in the differential diagnosis of spindle cell lesions of the urinary bladder. 1894 4

Secretory breast carcinomas (<0.15% of breast tumors) are associated with a characteristic morphology and a favorable prognosis. Remarkably, this entity is the only epithelial tumor of the breast with a balanced translocation, t(12;15), that creates an ETV6-NTRK3 gene fusion encoding chimeric tyrosine kinase also encountered in cellular mesoblastic nephroma and infantile fibrosarcoma. The aim of this study was to determine the phenotypic class (ie luminal A/B, ERBB2, basal-like) of secretory breast carcinoma. A series of six secretory breast carcinomas were identified in our files. The ETV6 rearrangement was confirmed in all cases by fluorescence in situ hybridization. Immunophenotype was assessed with anti-ER, PR, ERBB2, KIT, EGFR, E-cadherin, vimentin, PS100, smooth muscle actin, basal (CK5/6 and 14), luminal cytokeratins (CK8/18) and p63 antibodies. In situ and invasive components shared the same immunoprofile and were ER, PR, ERBB2 negative with expression of basal cytokeratins. ETV6 gene alterations were present in both in situ and invasive components, highlighting their genetic similarities. The immunoprofile data (triple-negative with expression of basal markers) showed that secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the phenotypic basal-like spectrum of breast carcinomas. These results support the hypothesis that secretory breast carcinomas have immunohistochemical and genetic features that distinguish them from other basal-like tumors of the breast.
...
PMID:Secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the basal-like carcinoma spectrum. 1901 1

The author reports herein two cases of ductal adenoma of the breast with an emphasis on immunohistochemistry. Both cases (patient 1, 58-year-old woman; patient 2, 78-year-old woman) were clinically suspected as carcinoma, and core biopsies were 'indeterminate' or 'suspicious for malignancy'. Excisional biopsy and wide excision were performed. Histologically, both cases were ductal adenomas composed of ductal epithelial cells and myoepithelial cells. Patient 1 had extensive apocrine metaplasia. Immunohistochemically, myoepithelial cells were noted in both cases; cytokeratin (CK) 14 and p63 were the most reliable myoepithelial markers, followed by CD10, alpha-smooth muscle actin and S100 protein. CK profile was as follows: positive expression of CK5/6, CK18, CK19, and high-molecular-weight CK, and negative expression of CK20. This CK profile was the same as that of non-tumorous ducts, suggesting that the CK profile does not alter in tumorigenesis. The tumor cells expressed p53 protein (case 1, positive cell percentage 5%; case 2, 7%), c-erbB2 (HER2/neu, 76%, 64%), CEA (5%, 0%), estrogen receptor (33%, 84%), but were negative for progesterone receptor. Ki-67 labeling was 5% and 3%, respectively. MUC apomucin expression was as follows: MUC1, 92%, 100%; MUC2, 0%, 0%; MUC5AC, 0%, 0%; and MUC6, 5%, 0%. Non-tumorous ducts expressed MUC1, but were negative for MUC2, MUC5AC and MUC6.
...
PMID:Ductal adenoma of the breast: immunohistochemistry of two cases. 1906 57

Traditional prognostic markers for breast cancer include estrogen receptor (ER), progesterone receptor (ER) and HER2/neu. Negative staining for these three markers defines the 'triple-negative' phenotype. By adding markers for cytokeratin 5/6 and EGFR, triple-negative breast cancers can be divided into 'basal-like' and 'normal-like' subgroups. We conducted immuno-staining on a panel of 958 patients with breast cancer, using all five markers and we followed the patients for distal recurrence and death. We compared rates of distal recurrence in the basal-like and normal-like subgroups with that of women with ER-positive breast cancer. Only 16 of 958 women had normal-like breast cancers. These cancers resembled basal-like cancers in that they had a high proliferative index, but the women with normal-like breast cancers resembled ER-positive women in terms of distant recurrence. The addition of CK5/6 and EGFR to the standard panel (ER/PR/HER2/neu) defines a small subgroup of women with normal-like breast cancer. The prognosis of these women may be superior to that of basal-like breast cancers but firm conclusions cannot be made.
...
PMID:Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers. 1918 11

Mammary Paget's disease (MPD) is a rare manifestation of breast carcinoma involving the nipple. Our objective was to identify molecular markers and molecular subtypes that may predict patients at high risk of developing MPD. Immunohistochemical (IHC) analyses were performed with antibodies to estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, epidermal growth factor receptor (EGFR), and several cytokeratins (CK5/6, CK14, CK17, CK8, CK18) on representative sections of 121 cases of ductal carcinoma of the breast, including 28 cases with MPD, 81 cases with neither MPD nor nipple involvement, and 12 cases of non-MPD with nipple involvement. The rates of receptor expression and subtype distributions of 3 IHC-based molecular classifications were compared among these groups. The results showed that: (1) MPD is more likely to be associated with ER- and PR-negative ductal carcinoma in situ (DCIS), but not invasive ductal carcinoma (IDC); (2) MPD is more likely to be associated with HER2-over expression subtype DCIS, but not IDC; and (3) carcinomas with non-MPD nipple involvement differ from those with MPD, since they are more likely to be ER- and PR-positive, HER2-negative, and luminal A subtype. In summary, different panels of markers should be used to predict MPD associated with different underlying lesions; for DCIS, the ER-negative, PR-negative, and HER2-subtype and not basal-like subtype is most predictive of MPD; for IDC, the luminal B-subtype is most predictive of MPD.
...
PMID:Different panels of markers should be used to predict mammary Paget's disease associated with in situ or invasive ductal carcinoma of the breast. 1920 36


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

---