Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral cancer is a major health problem in some parts of the world, especially in developing countries. Worldwide, the annual incidence exceeds 3,000,000 new cases. The main risk factors are tobacco and alcohol. However, dietary factors, viruses and possibly genetic predisposition have also been associated with oral cancer. Several oral lesions such as leukoplakia, erythroplakia and lichen planus carry an increased risk for malignant transformation in the oral cavity. Prognosis of oral cancer differs significantly between specific oral locations, with cancer of the lip for example having a much better prognosis than at the base of tongue or on the gingiva. Prognosis of intra-oral cancer is generally poor, with a five-year survival less than 50 percent. Local recurrences as well as lymph node metastases occur in a significant percentage of patients, while distant metastases are less frequent. Prognosis correlates mainly with the size of the lesion and the nodal status at the time of diagnosis, therefore early detection of small, stage-1 oral cancer can reduce mortality and morbidity. Oral lesions can be easily observed by direct visualization, however, knowledge of the differential diagnosis of oral lesions is mandatory for early diagnosis of malignant and pre-malignant lesions in the oral cavity. Use of screening and detection aids such as vital stains and Oral CDX can increase the number of cases diagnosed at an early stage, or even in the pre-malignant stage. Development of molecular markers can improve the early diagnosis and can help in predicting treatment response. New treatment modalities including tumor specific antibodies and gene therapy are emerging, giving more hope for patients with oral cancer. There is an important role for the dentist in both early diagnosis of pre-malignant and malignant lesions, and in prevention by educating the patients of the risks associated with tobacco, alcohol and dietary factors.
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PMID:[Update review on prevention and early diagnosis in oral cancer]. 1224 64

Lung metastases from colorectal carcinomas (CRC) can be resected with improved survival. The distinction between primary lung adenocarcinomas and metastases from CRC may sometimes be difficult, especially on cytologic specimens or small bronchoscopic biopsies. Immunohistochemistry may be of help in this setting: available markers include TTF-1 and SP-A, which are markers of lung origin, whereas there are no good markers of intestinal origin, besides cytokeratin 7 and 20 coexpression pattern, which is not very specific. The nuclear CDX-2 transcription factor, which is the product of a homeobox gene necessary for intestinal organogenesis, is expressed in normal colonic epithelia and most colorectal adenocarcinomas, and could potentially be of diagnostic usefulness. Our aim was to investigate CDX-2 immunohistochemical expression using a new monoclonal antibody and to verify if CDX-2 can be a reliable marker to identify the colorectal origin of lung metastases. CDX-2 expression was evaluated in formalin-fixed, paraffin-embedded samples of normal adult human tissues (50 samples) and in 299 surgically resected carcinomas of different origins, including 125 non-lung adenocarcinomas, 117 primary lung tumors, 5 mesotheliomas, and 52 adenocarcinomas metastatic to the lung. CDX-2 was also evaluated on a series of 20 bioptic and 10 cytologic specimens (5 cases of colorectal metastases to the lung, 5 cases of metastases from other organs, and 10 primary lung adenocarcinomas). In normal tissues CDX-2 immunoreactivity was observed only in ileal and colorectal epithelia. CDX-2 was expressed in almost all primary and metastatic CRC (88 of 90) and was never observed in primary lung tumors. CDX-2 was also expressed in a limited group of adenocarcinomas of other sites (gastric, biliopancreatic, and mucinous ovarian adenocarcinomas). CDX-2 could be easily detected in all bioptic and cytologic samples of CRC metastases. CDX-2 is a reliable, specific, and sensitive immunohistochemical marker of normal and neoplastic intestinal epithelium. CDX-2 can be easily applied to routine histologic and cytologic material and is therefore a useful marker in the differential diagnosis of primary versus metastatic adenocarcinomas in the lung, and among metastases from an unknown primary, supports intestinal origin.
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PMID:CDX-2 homeobox gene expression is a reliable marker of colorectal adenocarcinoma metastases to the lungs. 1450 2

The caudal-related homeobox transcription factor CDX2 regulates the differentiation of intestinal epithelial cells. Recent studies have suggested that CDX-2 immunoreactivity is strictly confined to benign and malignant intestinal epithelium. In the present study, we evaluated the prevalence of CDX2 immunoreactivity in a series of benign, borderline and malignant primary ovarian mucinous neoplasms. We tested 62 mucinous tumours of the ovary, including 28 benign cystadenomas, 18 borderline tumours, 16 adenocarcinomas, 35 serous and endometrioid ovarian lesions and 10 ovarian metastases of colonic adenocarcinoma. Overall, the CDX2 prevalence in primary mucinous tumours was 79%, including 20 of 28 (71.5%) cystadenomas, 14 of 18 (77.7%) borderline tumours and 15 of 16 (93.5%) adenocarcinomas. Immunoreactivity usually correlated with intestinal differentiation of tumour cells, although wide heterogeneity in the distribution of immunolabelled cells was noted. No immunoreactivity was observed in serous lesions; whereas, 1 of 13 (7.7%) endometrioid adenocarcinomas and all of the 10 metastatic colonic adenocarcinomas were immunostained. These results indicate that CDX2 is detectable in the majority of benign, borderline and malignant ovarian mucinous tumours and, therefore, makes this marker unsuitable when distinguishing primary from metastatic ovarian mucinous adenocarcinomas. However, CDX2 immunoreactivity could be useful in the distinction between endocervical and intestinal-type mucinous tumours of the ovary, which may have clinical relevance.
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PMID:CDX2 immunoreactivity in primary and metastatic ovarian mucinous tumours. 1457 39

CDX-2 is a homeobox gene product essential for intestinal development and differentiation. It can be used as a specific marker of colorectal adenocarcinomas and other tumors with intestinal differentiation, but little is known about its expression in endocrine and neuroendocrine (NE) cells and NE primary and metastatic tumors. Using the Cdx-2-88 monoclonal antibody, we evaluated CDX-2 expression in routine samples of 20 normal endocrine/NE tissues and of 299 samples of well-differentiated NE tumors (WDNET) and high-grade NE carcinomas (NEC) from different sites. For 17 cases, we examined primary and corresponding metastatic lesions. We also examined 8 cytologic samples of liver metastases derived from 4 ileal WDNETs, 1 lung WDNET, and 3 pancreatic endocrine tumors. CDX-2 mRNA expression with RT-PCR technique on frozen material was evaluated in 5 WDNETs. CDX-2 was expressed in normal NE cells of the intestine and gastric fundus. High CDX-2 expression was seen in all ileal and appendiceal WDNET, while low levels were seen in WDNETs from stomach, duodenum, and rectum; no reactivity was seen in other WDNETs. Low levels of CDX-2 expression were seen in one third of nonfunctioning pancreatic WDNET where it was more frequently observed in cases with metastatic disease (P = 0.002). CDX-2 was identified in all cytologic specimens of metastatic ileal WDNETs. CDX-2 mRNA analysis confirmed immunohistochemical results. CDX-2 was expressed at high levels in 81% of intestinal NEC. Unexpectedly, variable levels of expression of CDX-2 were seen also in 39% of NEC of other sites, without any relation with the site of origin. This reactivity frequently overlapped TTF-1 expression, suggesting deregulated expression of homeobox genes in NEC. The restricted pattern of CDX-2 expression may have diagnostic value in the identification of the primary site of a metastatic WDNET. Conversely, a limited diagnostic role is suggested for CDX-2 in NEC because of its frequent expression in nongastrointestinal tumors.
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PMID:CDX-2 homeobox gene product expression in neuroendocrine tumors: its role as a marker of intestinal neuroendocrine tumors. 1531 16

Classical midgut carcinoids are serotonin-secreting tumors derived from enterochromaffin cells in the gut. Metastatic disease represents a therapeutic challenge and immunotherapy implies a novel approach for treatment. In order to define antigens suitable for T-cell therapy with a preferential expression in midgut carcinoid tissue a broad screening of genes with preferential neuroendocrine restriction, genes described as over-expressed in various malignancies, and genes encoding cancer-testis associated antigens was performed. The expression of 32 genes was analyzed by reverse transcription polymerase chain reaction (RT-PCR) in 28 midgut carcinoid specimens, in the cell line BON and in normal tissues. Immunohistochemistry (IHC) was used to evaluate protein expression. Expression is shown of genes that have previously not been observed in midgut carcinoid tumors, such as Survivin and GAGEs. Also the expression is confirmed of genes that encode pivotal proteins in enterochromaffin cells, such as TPH1 and VMAT1, and their tissue-restricted expression is indicated. In addition, gene expression of IA-2 and CDX-2 in normal gastrointestinal (GI) tract and in tumor is shown. Protein expression of TPH, VMAT1, and Survivin was detected in tumor tissue. This study elucidates that TPH1, VMAT1, and Survivin should be further investigated as potential target antigens for T cell-mediated immunotherapy of midgut carcinoids.
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PMID:Gene expression in midgut carcinoid tumors: potential targets for immunotherapy. 1584 4

Signet-ring adenocarcinoma is an aggressive form of primary bladder adenocarcinoma that has been associated with poor outcomes. The utility of immunohistochemical markers in tumors with signet-ring morphology may vary from more typical adenocarcinomas arising at the same location, although this has not been examined in bladder adenocarcinoma. We examined a series of bladder adenocarcinomas to determine the impact of signet-ring cell features on clinical outcomes and immunohistochemical findings. We identified 25 patients with bladder adenocarcinoma, ranging in age from 28 to 78 years (mean, 57 years) and with a male-female ratio of 18:7. Six cases were urachal in origin. Signet-ring cells occurred in 19 of 25 bladder adenocarcinomas (76%) and ranged from 5% to 100% of tumor volume, with most tumors demonstrating more than 60% signet-ring cell differentiation (15/19), when present. Regional lymph node metastases were present in 8 of 19 patients (42%) who underwent cystectomy. The percentage of tumor containing signet-ring cells was significantly associated with the presence of adverse pathologic features (defined as unresectable primary tumor or regional lymph node metastasis, P = .013) and decreased overall survival (P = .034), and the latter remained significant in multivariable analysis after adjusting for positive soft tissue margins (P = .026). A comparison between immunohistochemical markers frequently used to analyze bladder adenocarcinoma demonstrated decreased expression of several markers in signet-ring (n = 9) versus colonic-type (n = 8) morphology, including CDX-2, beta-catenin, and E-cadherin, although these results did not reach statistical significance. In summary, the extent of signet-ring differentiation in bladder adenocarcinoma is associated with worsened survival and higher stage disease; the utility of immunohistochemical analysis in foci consisting of predominant signet-ring cells may be limited, although further studies that address this finding are needed.
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PMID:Clinicopathologic features and utility of immunohistochemical markers in signet-ring cell adenocarcinoma of the bladder. 1878 86

Carcinoid tumors of the ovary are rare neoplasms that may be primary or metastatic. Clinicopathologic features such as unilaterality and early stage favor a primary ovarian neoplasm but in the absence of other teratomatous elements it may be difficult or impossible to determine whether an ovarian carcinoid is primary or metastatic. CDX-2 is a marker of intestinal differentiation that has been proposed as a marker of midgut origin for metastatic carcinoids. Its expression has not been tested in ovarian carcinoids. Additional markers of potential help in defining the origin of a carcinoid include cytokeratin (CK) 20, CK7, and thyroid transcription factor (TTF-1), none of which have been studied in ovarian carcinoids. We evaluated the diagnostic utility of CDX-2, CK20, CK7, and TTF-1 as well as conventional clinicopathologic features in determining the site of origin in 26 ovarian carcinoids (16 primary and 10 metastatic from midgut). Non-neoplastic premenopausal ovaries (n=10) served as controls. All primary ovarian carcinoids were unilateral whereas only 3/10 metastatic carcinoids were unilateral. Multinodular growth occurred in 6/10 metastatic carcinoids but not in any primary carcinoid. The average size of primary ovarian carcinoids was 3.4 cm (range: 0.2-13.5 cm) versus 10.2 cm for metastatic carcinoids (range: 4-32 cm). Of the primary ovarian carcinoids, 12/16 were 3 cm or smaller whereas all metastatic carcinoids were 4 cm or larger. Teratomatous elements were present in association with 10/16 primary ovarian carcinoids, whereas none were present in any metastatic carcinoid. The primary ovarian carcinoid types were insular (n=6), trabecular (n=3), strumal (n=6, of which 5 were trabecular pattern and 1 was insular pattern) or mucinous (n=1). CDX-2 was not expressed in any cells in normal ovaries. Among primary ovarian neoplasms, there was diffuse nuclear CDX-2 expression in 4/6 insular, 0/3 trabecular, 1/6 strumal (1/1 insular pattern and 0/5 trabecular pattern strumal carcinoids), and 1/1 mucinous carcinoids. All metastatic carcinoids, except for two of mucinous type, were insular. CDX-2 was diffusely and strongly expressed in all 8 metastatic insular carcinoids and in both metastatic mucinous carcinoids. None of the metastases was trabecular in type but 12 primary hindgut or foregut trabecular carcinoids were evaluated and all were negative for CDX-2. None of the ovarian carcinoids expressed TTF-1, CK7, or CK20, except for the primary and metastatic mucinous carcinoids, all of which were CK20-positive. These results demonstrate that CDX-2 cannot be used to determine if a carcinoid is primary in the ovary or metastatic from the intestine as insular and mucinous types of either origin express this marker. Trabecular carcinoids of either origin lack CDX-2 expression. CK20, CK7, or TTF-1 do not have diagnostic utility in this context. Conventional clinicopathologic features (unilaterality, lack of multinodular growth, early stage, presence of teratomatous elements, and size 3 cm or smaller) are the most helpful findings in suggesting a primary origin for an ovarian carcinoid tumor.
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PMID:Primary ovarian carcinoid tumors may express CDX-2: a potential pitfall in distinction from metastatic intestinal carcinoid tumors involving the ovary. 1904 9

Uveal melanoma is an aggressive disease without effective adjuvant therapy for metastases. Despite genomic differences between cutaneous and uveal melanomas, therapies based on shared biological factors could be effective against both tumor types. High expression of glycoprotein-NMB (GPNMB) in cutaneous melanomas led to the development of CDX-011 (glembatumumab vedotin), a fully human monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin monomethylauristatin E. Ongoing phase II trials suggest that CDX-011 has activity against advanced cutaneous melanomas. To determine the potential role of CDX-011 in uveal melanomas, we studied their GPNMB expression. Paraffin-embedded tissues from 22 uveal melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated CDX-011 (unconjugated) antibody. Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21 tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of tumor cells with variable intensity (5 tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18 tumors (61.1%) expressed GPNMB in >or=50% of cells. Spectral imaging showed diffuse CDX-011 (unconjugated) reactivity in the remaining case. Uveal melanoma, like cutaneous melanoma, commonly expresses GPNMB. Ongoing clinical trials of CDX-011 should be extended to patients with metastatic uveal melanoma to determine potential efficacy in this subset of patients with melanoma.
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PMID:GPNMB expression in uveal melanoma: a potential for targeted therapy. 2037 21

Pathologic and prognostic data of nine patients with mitochondrion-rich carcinomas (MRC) were compared retrospectively to data of 101 patients with conventional gastric adenocarcinomas. MRC was defined as a tumour composed predominantly, or entirely, of columnar adenocarcinoma cells with eosinophilic cytoplasm and a strong supranuclear immunoreactivity for antimitochondrial antibody. Electron microscopy confirmed supranuclear distribution of mitochondria in MRC while immunostaining pattern was irregular or absent in the remaining 101 cases. MRC exhibited a tubulopapillary or cribriform growth pattern with focal infiltration of neutrophils in the tumour stroma. Prominent necrosis was present including segmental and intraluminal "dirty necrosis", while mitotic and ki-67 proliferative rates were low. MRC showed immunohistochemical findings compatible with gastric differentiation (CK7+/CK20-/CDX-) When MRC were compared with non-MRC carcinomas, tumour size (< 4 cm vs >4 cm, P < 0.01) , frequency of lymph node metastases (11% vs. 80%, P < 0.01), low stage (I, II) at diagnosis (100% vs. 56%, P < 0.01), Goseki's group I (100% vs. 6%, P < 0.01), and better survival (0% vs. 70%, P < 0.01) differed significantly. Our results suggest that MRC of the stomach may be considered a low-grade malignancy with an excellent prognosis.
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PMID:Mitochondrion-rich differentiated adenocarcinomas of the stomach: clinicopathological, immunohistochemical and electron microscopy study of nine cases. 2039 47

It has been proposed in human colorectal cancers (CRC) a minority subset of cancer cells within tumors able to initiate tumor growth, defined as cancer stem cells (CSC). Solid human primary colonic and its ovarian metastatic cancer tissues were collected from fresh surgical samples and subsequent xenografts were established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The resulting tumors were disaggregated into single-cell suspensions and a CD133(-) cell line (NANK) was newly established and analyzed by flow cytometry. Surface markers of progenitor cells were immunophenotypically analyzed, and expression of stem cell and cancer-related genes was characterized. Secreted angiogenesis-associated molecules were investigated by proteomic array technology. Finally, different numbers of NANK were implanted and their tumor-initiating properties were investigated in NOD/SCID mice. Intraperitoneal injection of NANK in NOD/SCID mice induced tumors with developing progressive peritoneal dissemination and ascites. NANK cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. Noticeably, NANK lacked the expression of conventional CSC markers CD133 and CD44, self-renewal genes Oct-4 and Nanog, but showed the expression of an important gastrointestinal development marker CDX-2 and BMI-1 that is essential in regulating the proliferative activity of normal and leukemic stem cells. In addition, NANK secreted high amounts of important angiogenic cytokines. These results provide a novel and extensive model in human CSC for studying the generation and maintenance of phenotypic heterogeneity in CRC.
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PMID:Isolation and propagation of a human CD133(-) colon tumor-derived cell line with tumorigenic and angiogenic properties. 2058 45


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