Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cathepsin D, an aspartic proteinase, correlates with invasion and metastasis in breast cancer and with poor prognosis. In the present study, we examined the immunohistological expression of cathepsin D in both primary (5 cases) and skin-metastatic breast cancers (13 cases) and compared it to those in gastric (2 cases) and lung (4 cases), and primary eccrine cancers (3 cases). All breast and gastric cancers were adenocarcinomas. The 2 gastric cancers were poorly differentiated, while the 4 lung cancers consisted of 2 poorly differentiated adenocarcinomas, 1 poorly differentiated large cell carcinoma, and 1 moderately to poorly differentiated squamous cell carcinoma. We also surveyed the immunohistological distribution of cathepsin B, carcinoembryonic antigen, gross cystic disease fluid protein-15, c-erbB-2, and estrogen receptor. In almost all breast cancer samples, the cancer cells demonstrated strong expression of cathepsin D in the cytoplasm, but weak staining patterns with other antibodies. Gastric and lung cancer cells did not respond with cathepsin D (except one metastatic lung cancer) or the other immunohistological markers. Since cathepsin D is strongly expressed in primary and metastatic lesions of breast cancer, cathepsin D could be useful as an adjunct to a panel of immunohistochemical stains in determining the primary site of origin of metastatic cancer in the skin.
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PMID:Cathepsin D expression in skin metastasis of breast cancer. 976 21

The relative expression of mucin antigens MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC7 and glycoprotein antigens KSA, carcinoembryonic antigen, prostate-specific membrane antigen (PSMA), HER-2/neu, and human chorionic gonadotropin-beta on different cancers and normal tissues is difficult to determine from available reports. We have compared the distribution of these antigens by immunohistology on a broad range of malignant and normal tissues. MUC1 expression was most intense in cancers of breast, lung, ovarian, and endometrial origin; MUC2 was most intense in cancers of colon and prostate origin; and MUC5AC was most intense in cancers of breast and gastric origin. MUC4 was intensely expressed in 50% of cancers of colon and pancreas origin, and MUC3, MUC5B, and MUC7 were expressed in a variety of epithelial cancers, but not so intensely. KSA was intensely and uniformly expressed on all epithelial cancers; carcinoembryonic antigen was expressed in most cancers of breast, lung, colon, pancreas, and gastric origin; and PSMA was expressed only in cancers of prostate origin. Human chorionic gonadotropin-beta was expressed on the majority of sarcomas and cancers of breast, lung, and pancreas origin, although intense staining was not seen. Staining on normal tissues was restricted to one or many normal epithelial tissues ranging from MUC3, MUC4, and PSMA, which were expressed only on epithelia of pancreas, stomach, and prostate origin, respectively, to MUC1 and KSA, which were expressed on most normal epithelia. Expression was restricted to the secretory borders of these epithelia while stroma and other normal tissues were completely negative. These results plus the results of the two previous papers (S. Zhang et al, Int. J. Cancer, 73: 42-49, 1997; S. Zhang et al., Int. J. Cancer, 73: 50-56, 1997) in this series provide the basis for selection of multiple cell surface antigens as targets for antibody-mediated attack against these cancers.
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PMID:Selection of tumor antigens as targets for immune attack using immunohistochemistry: protein antigens. 982 29

The human carcinoembryonic antigen (CEA) and HER-2/neu are potential target antigens for CTL specific immunotherapy for common malignancies such as breast, lung, colon, and gastric carcinomas. Several CTL epitopes restricted by HLA-A2, the most common human histocompatibility molecule, have been previously reported. However, to develop CTL-based immunotherapies for the general population, it is necessary to identify epitopes restricted by other common histocompatibility alleles. Here, we describe two HLA-A3-restricted CTL epitopes from the CEA and HER-2/neu antigens. HLA-A3 binding synthetic peptides from CEA and HER-2/neu were tested for immunogenicity by in vitro primary CTL induction protocol using peripheral blood mononuclear cells from normal healthy volunteers. One peptide from CEA (CEA[9(61)]: HLFGYSWYK) and one peptide from HER-2/neu (HER2[9(754)]: VLRENTSPK) were shown to induce CTL that was capable of killing a tumor cell line expressing HLA-A3 and the corresponding tumor-associated antigen. Additional MHC binding studies with the most common HLA molecules belonging to the HLA-A3 superfamily (HLA-A*1101, -A*3101, -A*3301, and -A*6801), demonstrated that CEA[9(61)] binds five of five A3 supertype molecules with high affinity, and the HER2[9(754)] epitope was able to bind to four of the same five alleles. These results indicate that these two new CTL epitopes should be immunogenic in individuals expressing either HLA-A3, or other members of the HLA-A3 superfamily.
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PMID:Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. 992 58

Over the past 2 decades, numerous anticancer antibodies against different molecular targets and labeled with different gamma-emitting radionuclides have been studied in human tumor xenografts and in clinical trials. In breast cancer, these molecular targets have included principally tumor-associated antigens, such as carcinoembryonic antigen (CEA) and the polymorphic epithelial mucin antigen, MUC1, and more recently the growth factor receptors, EGF-R and HER-2/neu. No antibody-based agent has yet been approved for clinical use in the diagnosis of mammary carcinoma, because few trials have addressed the issue of clinical use of these imaging agents in the management of breast cancer patients. Recently, the CEA antibody Fab' fragment approved for colorectal cancer detection, Arcitumomab (CEA-Scan, [Immunomedics, Morris Plains, NJ]), has been found to image both palpable and nonpalpable breast lesions that were suspicious on screening mammograms. Results to date indicate that Arcitumomab can complement mammography by providing a high specificity and positive predictive value, thus indicating when a patient with an abnormal mammogram may proceed directly to definitive surgery without an intermediate diagnostic biopsy. Breast cancer immunoscintigraphy holds promise for advancing toward immunoPET, which should combine the specificity of antibodies with the high sensitivity and resolution of PET. It is also the foundation of breast cancer radioimmunotherapy with humanized antibodies against CEA and MUC1, as well as other immunotherapy strategies.
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PMID:Breast cancer imaging with radiolabeled antibodies. 999 Jun 82

Salivary duct carcinoma is a highly malignant adenocarcinoma of salivary origin. Its pathologic features are distinct from the other salivary gland tumors and bear a remarkable histologic resemblance to ductal breast carcinoma. The clinical course is rapid and the prognosis is dismal. Aggressive therapy is warranted, including primary tumor resection, cervical neck dissection, and radiotherapy. We present a case of salivary duct carcinoma of parotid origin with a very long-term evolution in clear contrast to its supposed aggressiveness. Tumor cells expressed low- and high-molecular-weight cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, and c-erbB-2 but not estrogen and progesterone receptors, actin, and S-100.
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PMID:Salivary duct carcinoma: an unusual case of long-term evolution. 1055 56

C-erbB-2 oncoprotein (ErbB-2 protein)and carcinoembryonic antigen (CEA)were simultaneously evaluated in the breast cyst fluid of 6 patients with intracystic cancer, 6 patients with intracystic papilloma, and 42 patients with gross cystic disease. A combination test, using 12 ng of ErbB-2 protein and 150 ng of CEA/ml of cyst fluid, respectively, as cutoff values resulted in a positive detection rate of 83%(5/6 cases) for intracystic breast cancer. Two of the 6 patients with intracystic papilloma and 2 of the 42 patients with gross cystic disease were positive. In addition, elevated levels of these markers in cyst fluid correlated well with the expression of these antigens in the corresponding tumor. Thus, it can be concluded that measurements of ErbB-2 protein and CEA aid in the diagnosis of intracystic breast cancer, and the assay of ErbB-2 protein is valuable for detecting tumors in which this protein is overexpressed.
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PMID:Simultaneous Assay of ErbB-2 Protein and Carcinoembryonic Antigen in Cyst Fluid as an Aid in Diagnosing Cystic Lesions of the Breast. 1109 3

Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index.
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PMID:Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. 1143 14

Clear cell carcinoma of the gynecologic tract has been defined in terms of its clinical and histologic features; however, its immunophenotypic profile has not been fully characterized. Seventeen cases of primary clear cell carcinoma from various sites within the female genital tract (11 ovary, 5 uterus, 1 vagina) were analyzed by immunohistochemistry. These tumors were assessed for the expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), low and high molecular weight cytokeratin, (CAM5.2 and 34 beta E12, respectively), carcinoembryonic antigen (CEA), Leu-M1, vimentin, estrogen receptor (ER), progesterone receptor (PR), bcl-2, p53, HER-2/neu, and CA-125. The characteristic immunoprofile for all sites was positivity for CK7, CAM5.2, 34 beta E12, CEA, Leu-M1, vimentin, bcl-2, p53, and CA-125; variably positivity for ER and HER-2/neu; and negativity for CK20 and PR. For comparison, two cases of urologic clear cell carcinoma (1 bladder, 1 urethra) were also studied, and their profile was found to be similar to the gynecologic cases. Aside from minor differences, clear cell carcinoma appears to have the same immunophenotype regardless of whether it originates in the endometrium, ovary, or genitourinary tract. Much of its profile is similar to other gynecologic adenocarcinomas, but some of the markers studied may be useful in the differential diagnosis of this tumor.
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PMID:Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract. 1144 1

Many serological markers have been utilized to indicate the status, risk, or presence of breast cancer. In May 1996, the American Society of Clinical Oncology (ASCO) convened a Tumor Marker Panel and determined clinical practice guidelines for the use of tumor markers in breast cancer. Eight markers containing carcinoembryonic antigen (CEA) and CA15-3 were evaluated and assigned by expert reviewers to be valuable markers of breast cancer. CA15-3 recognizes a mucin-like glycoprotein, MUC-1, which is frequently expressed in breast cancer tissues. BCA225, which may recognize antigens similar to MUC-1 glycoprotein, are sensitive and specific markers for breast cancer. However, it is not recommended to measure the 2 markers in combination. The measurement of carboxy-terminal telopeptide of type I collagen (I CTP) is worthwhile as a serological diagnostic method of bone metastasis from breast cancer. Other markers such as erbB-2, CYFRA 21-1 and PTHrP are candidates for clinical utilization as tumor markers in breast cancer.
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PMID:[Tumor markers in breast cancer]. 1147 35

Multiple atypical adenomatous hyperplasia (AAH) of both lungs in a 72-year-old male, detected by computed tomography, is reported. The lesions of the right lung were resected for diagnosis via video-assisted thoracoscopic surgery (VATS). The resected specimen had 22 AAH lesions up to 10 mm in size. For nine of these lesions, the expressions of carcinoembryonic antigen (CEA), c-erbB-2 oncoprotein and p53 gene product were examined by immunohistochemistry and the loss of heterozygosity (LOH) on chromosomes was investigated by polymerase chain reaction analysis. These lesions showed a variety of expressions for CEA, c-erbB-2 and p53 oncoprotein. Three of the nine lesions showed LOH on chromosome 13q, although this was not exhibited in the largest one. These results indicate that each AAH in this case has independent genetic abnormalities and is multicentric.
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PMID:A case of multiple atypical adenomatous hyperplasia of the lung detected by computed tomography. 1169 23


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