bromochloroacetic-acid and Digestive-System-Neoplasms

This review is concerned with the usefulness and the problem of biomarkers for cancer of digestive organs. Carcinoembryonic antigen (CEA) is a most popular and useful tumor marker for cancer of digestive organs. Squamous cell carcinoma (SCC) antigen and CYFRA have been reported as a useful tumor marker for esophageal cancer. CEA and CA 19-9 are a good prognostic factor in gastric cancer patients. The post-operative increase of serum CEA can be a predictive marker for the patients of colorectal cancer. Development of a radioimmunoassay for highly sensitive detection of tumor markers, they are considered to be useful for monitoring after treatment. But are not useful for the early diagnosis. The diagnosis of hepatocellular carcinoma (HCC) is based mainly on serological markers, such as alpha-fetoprotein and PIVKA-II. The two are useful complementary markers of HCC because they do not correlate with each other. But the problem of the false-positive rate for the patients with chronic hepatitis or liver cirrhosis is still remained. A typical marker of pancreatic and bile duct cancer is carbohydrate antigen, but the sensitivity of these markers is only 50%. Recent molecular biological analysis may be used as effective biomarkers in the diagnosis, prognosis, therapy, and risk assessment of digestive cancer.

Topics: alpha-Fetoproteins; Antigens, CD19; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Colorectal Neoplasms; Digestive System Neoplasms; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Lewis X Antigen; Liver Neoplasms; Pancreatic Neoplasms; Prognosis; Protein Precursors; Prothrombin; Stomach Neoplasms

Sarcomatoid carcinoma of the upper aerodigestive tract continues to be one of the most difficult diagnostic challenges for surgical pathologists. Histogenesis has been settled in favor of a divergent (mesenchymal) differentiation of a carcinoma, most often a squamous cell carcinoma. Finding the carcinoma and/or its immunohistochemical marker in the metaplastic cells establishes the diagnosis. There are, however, lesions that can simulate sarcomatoid carcinomas to varying degrees, and in which neither a definable carcinoma nor immunohistochemical evidence of one can be found. Such lesions fall into several categories: 1. benign reactive lesions, 2. inflammatory myofibroblastic tumors, 3. sarcomas, usually low-grade, 4. atypical pseudosarcomatous proliferation. The clinicopathologic considerations of sarcomatoid carcinomas are presented in this context and include immunohistochemical findings, prognostic factors, and biologic course.

Topics: Carcinosarcoma; Cell Nucleus; Diagnosis, Differential; Digestive System Neoplasms; Epithelium; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Mesoderm; Mouth Neoplasms; Neoplasms, Muscle Tissue; Phenotype; Prognosis; Respiratory Tract Neoplasms

Topics: Adult; Digestive System Neoplasms; Endocrine Gland Neoplasms; Epithelium; Female; Humans; Keratins; Lung Neoplasms; Male; Neoplasms; Precancerous Conditions; Skin Neoplasms; Urogenital Neoplasms

Intraepithelial neoplasia of the upper aerodigestive tract (UADT), including both histologically defined dysplasia and carcinoma in situ (CIS), appears to fall into two broad groups similar to intraepithelial neoplasia of other squamous mucosae, keratinizing and non-keratinizing. Keratinizing dysplasia/CIS is common in the UADT and uncommon in other sites such as the cervix. In general, keratinizing epithelial proliferation results in thick epithelium, usually with prominent superficial keratin expression with a whitish or "leukoplakic" clinical appearance. Although most clinical leukoplakic changes in the UADT mucosa do not represent neoplastic transformation and do not progress to invasive carcinoma, keratinizing dysplasia, defined by nuclear atypism and maturation alterations, has an appreciable progression to invasive carcinoma. Non-keratinizing dysplasia/CIS, common in the cervix, is less common in the UADT mucosa. In general, non-keratinizing epithelial alterations consist of a proliferation of incompletely differentiated cells as measured by a spectrum of maturation markers. These changes result in a thin epithelium which commonly has a red, or clinically "erythroplakic," appearance. Non-keratinizing dysplasias are less common, but are more likely to harbor high grade dysplasia or early invasive carcinoma.

Topics: Animals; Carcinoma, Verrucous; Digestive System Neoplasms; Epithelium; Erythroplasia; Humans; Keratins; Leukoplakia; Precancerous Conditions; Respiratory Tract Neoplasms

Epithelial cell intermediate filaments, or cytokeratins, are excellent markers for cell differentiation. During embryogenesis, cytokeratins specific of a stage of differentiation step always become detectable before corresponding morphologic changes: for instance, cytokeratins 5 and 14 are found around the eight week, shortly before stratification of the epithelium occurs, and cytokeratins 1 and 10 are produced before morphologic evidence of keratinization becomes detectable. Among potential diagnostic applications, analysis of cytokeratin patterns of epidermal cells desquamated in the amniotic fluid may provide earlier and less invasive diagnosis than fetoscopic biopsies. Similarly, a review of cytokeratins expressed in a variety of epithelial diseases (involving the epidermis, digestive tract, respiratory tract, urogenital tract, or breast) demonstrated persistence of the original tissue pattern in some instances (this was the case for the majority of simple epithelia) but not in others (complex epithelia). This suggests that cytokeratins may prove valuable as markers for specific tumor stages or types and may provide earlier information than morphologic studies.

Topics: Breast Neoplasms; Digestive System Neoplasms; Epidermis; Female; Genital Neoplasms, Female; Genital Neoplasms, Male; Humans; Keratins; Male; Psoriasis; Skin Neoplasms

Topics: Adenocarcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cells, Cultured; Digestive System Neoplasms; Epithelium; Female; Histocytochemistry; Humans; Keratins; Molecular Weight; Neoplasms

Few data are available regarding the epithelial to mesenchymal transition (EMT) /mesenchymal to epitheilal transition (MET) in the liver metastasis of digestive cancers. The aim of this study was to establish EMT/MET metastatic tumor cell plasticity according to the histological growth pattern of liver metastases.. Biopsies from 25 patients with liver metastasis (desmoplastic, replacement and pushing type) were evaluated. Double immunostaining of E-cadherin/vimentin, keratin 8,18/vimentin and E-cadherin/ keratin 8,18 were performed.. The following cell types were noted: epithelial, mesenchymal, non-differentiated and differentiated hybrid mesenchymal/ epithelial and non-hybrid phenotype. All cases had mesenchymal/ epithelial phenotype cells. A significant correlation was found between the non-differentiated hybrid mesenchymal/ epithelial phenotype metastatic cells and histological growth pattern for gastric and colorectal cancer.. A MET-targeting strategy, in conjunction with conventional chemotherapy, may be useful for the treatment of liver metastases.

Topics: Antigens, CD; Cadherins; Cell Plasticity; Colorectal Neoplasms; Digestive System Neoplasms; Epithelial-Mesenchymal Transition; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Vimentin

(1) To test whether in genomewide expression profiling differentially expressed genes were also distinct on the protein level including KIT and PDGFRA (2) to correlate the expression with clinicopathological parameters (3) to identify activating mutations that might be eligible for tyrosine kinase inhibitor therapy by mutational analysis of tumors with high expression.. Gastroenteropancreatic neuroendocrine tumors (GEP NETs) from 119 patients were analyzed for protein expression of ten biomarkers. Mutational analysis of KIT (exon 9, 13, 11 and 17) and PDGFRA (exons 12 and 18) was performed on those samples that showed high protein expression.. High KIT expression was observed in 13% of all specimens, PDGFRA in 33%, CK19 in 26%, CK7 in 2%, CK20 in 5%, S100 in 6%, CD56 in 25%, Chromogranin in 55%, and Synapthophysin in 80%. High expression of KIT and PDGFRA was significantly correlated with shorter disease-specific survival (P = 0.003, P = 0.018, respectively). In multivariate analysis expression of PDGFRA, radicality of surgical treatment and WHO grading influenced disease-specific 10-year survival independently (P = 0.032, P = 0.001 and P = 0.008, respectively). Mutational analysis of highly expressed specimens (n = 51) reveals a novel mutation of KIT in exon 11 (K558N_V559insP) in a well-differentiated metastatic pancreatic neuroendocrine tumor.. High expression of KIT and PDGFRA was significantly correlated with shorter patients survival and could serve as prognostic marker. Mutations of the KIT gene might open new avenues for tyrosine kinase inhibitor therapy in a subset of patients with advanced pancreatic neuroendocrine tumors.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; CD56 Antigen; Chromogranin A; Digestive System Neoplasms; DNA Mutational Analysis; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intestinal Neoplasms; Kaplan-Meier Estimate; Keratins; Ki-67 Antigen; Male; Middle Aged; Mutation; Neuroendocrine Tumors; Odds Ratio; Pancreatic Neoplasms; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; S100 Proteins; Stomach Neoplasms; Synaptophysin; Up-Regulation

To determine the most optimal treatment of cancer patients, it is fundamental to classify human carcinomas according to their primary anatomical site of origin. As for some patients, it is difficult to identify cancers occurring at obscure location and overlapping adjacent sites. The aim of this study is to partition the primary site of 486 patients in cancers of the digestive system by the expression pattern of the mucins and cytokeratins typifying each site. The expressions of MUC1, MUC2, MUC5AC, MUC6, CK7, CK8, CK13, CK14, CK18, CK19 and CK20 were evaluated immunohistochemically in 426 adenocarcinomas and 60 hepatocellular carcinomas using the tissue-array method. The finding of MUC series showed their characteristics in case of MUC2 in the appendix cancer and MUC1 and 5AC in pancreas cancer. As for CKs 7, 13, and 19, and 20 had a feature in cancers of common bile duct, liver, and appendix, respectively. We classified cancers in 11 sites by characteristic expression of antibodies. The sensitivity, specificity, positive predictive value, and diagnostic efficacy of significant antibodies were calculated with deducing the dichotomous tree made by SPSS 10.0. Six of 11 antibodies, CK 7, CK13, CK19, CK20, MUC1, and MUC5AC distinguished 6 groups from 11 sites. We also executed the clustering of cancers to investigate total relationship among cancers. They fell into three categories, which corresponded to embryologic origin. Unlike other sites, the small intestine and colorectum cancers expressed significantly different patterns to their sublocations. Mucins and CKs showed expression patterns to classify the primary sites of digestive cancers and may be helpful in predicting the primary sites of digestive cancers.

Topics: Adenocarcinoma; Biomarkers, Tumor; Cluster Analysis; Decision Trees; Digestive System Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Mucins; Protein Array Analysis; Tissue Embedding

Basaloid-squamous carcinoma of the larynx, pharynx and base of tongue and the so-called adenoid cystic carcinoma of the oesophagus are rare but distinctive tumours associated with a grave prognosis. They occur most commonly in elderly males and present at an advanced stage. Our study of four such laryngeal tumours and five such oesophageal tumours shows that they are histologically and immunohistochemically identical, providing support for the idea that they are the same tumour type. They show a biphasic pattern in which basaloid tumour is intimately associated with a neoplastic squamous component which can be invasive or in situ. The basaloid component is in the form of invasive lobules with frequent comedo-necrosis and hyalinization. The constituent cells possess pale pleomorphic nuclei with frequent mitoses. Immunoreactivity for cytokeratin in the basaloid component is remarkable for its absence or weak and focal nature. Review of the literature shows that only a few cases of 'adenoid cystic carcinoma' of the oesophagus are bona fide examples of adenoid cystic carcinoma as it occurs in the salivary glands, while the others are identical to basaloid-squamous carcinoma of the upper aerodigestive tract. Their distinction is important because genuine adenoid cystic carcinoma is much less aggressive than basaloid-squamous carcinoma.

Topics: Actins; Aged; Antibodies; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Carcinoma, Basosquamous; Diagnosis, Differential; Digestive System Neoplasms; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Pharyngeal Neoplasms; Prognosis; S100 Proteins; Vimentin

Frozen sections of 48 squamous cell carcinomas and seven undifferentiated carcinomas of the upper aerodigestive tract were investigated immunohistochemically with monoclonal antibodies specific for keratin, vimentin, desmin, neurofilaments, and glial fibrillary acidic proteins. In nine squamous cell carcinomas (19%) and six undifferentiated carcinomas (86%) obtained before treatment coexpression of keratin and vimentin was detected in some tumor cells by double immunofluorescence studies. Nine squamous cell carcinomas expressed neurofilaments in scattered tumor cells. Coexpression of vimentin or neurofilaments was seen especially in the peripheral cell layer of the tumor nests and did not seem to correlate with the degree of differentiation. Three undifferentiated carcinomas additionally expressed desmin, and one tumor contained neurofilaments. Glial fibrillary acidic proteins were not detected. Increased coexpression of keratin with vimentin, desmin, or neurofilaments was seen in some tumors that were studied before and after radiation/chemotherapy, suggesting that the intermediate filament profile of tumor cells can be altered by external influences.

Topics: Carcinoma, Squamous Cell; Cytoskeleton; Desmin; Diagnosis, Differential; Digestive System Neoplasms; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Microscopy, Electron; Vimentin

Human epithelial cells contain, intermediate-sized filaments formed by polypeptides related to epidermal alpha-keratin ("cytokeratins") which are expressed in different combinations in different epithelia. Using cytoskeletal proteins from human biopsies and autopsies we have examined, by two-dimensional gel electrophoresis and immunoblotting experiments, the cytokeratin polypeptide patterns of diverse primary and metastatic carcinomas and have compared them with those of corresponding normal epithelial tissues and cultured cells. Five groups of carcinoma cytokeratin patterns can be discriminated. (1) Cytokeratins typical of simple epithelia (polypeptides Nos. 7, 8, 18, 19) are expressed, in various combinations, by many adenocarcinomas, for example those of gastrointestinal tract. (2) Cytokeratins typical of stratified epithelia (Nos. 1, 5, 6, 10, 11, 14-17) are found, in various combinations, in squamous cell carcinomas of skin and tongue. (3) Complex patterns showing polypeptides Nos. 7, 8, 18, 19, and one basic component (No. 5 or 6) are detected in certain carcinomas of the respiratory tract and the breast. (4) Complex patterns containing cytokeratins widespread in stratified epithelia (Nos. 4-6, 14-17) as well as components Nos. 8 and 19 occur in diverse squamous cell carcinomas derived from non-cornified stratified epithelia, with or without additional small amounts of cytokeratin No. 18. (5) Patterns of unusually high complexity can be found in some rare tumors as is shown for a cloacogenic carcinoma. No significant qualitative changes of expression of cytokeratins were found when primary tumors and metastases were compared. When compared with cytokeratin patterns of normal epithelia, carcinomas of the first type usually display a high degree of relatedness to the tissue of origin. Other carcinomas do not express some of the cytokeratins present in the tissue of their origin and, vice versa, certain components which are minor or apparently absent in normal tissue are major cytokeratins in the corresponding tumor. These differences may be explained by cell type selection during carcinogenesis, but changes of expression during tumor development cannot be categorically excluded. The possibility of cell type heterogeneity within a given tumor is also discussed. Similarly complex patterns of cytokeratin polypeptides have been noted in certain cultured human carcinoma cell lines (e.g., A-431, RPMI 2650, Detroit 562, A-549) and can also be observed in cel

Topics: Breast Neoplasms; Carcinoma, Squamous Cell; Cell Line; Cytoskeleton; Digestive System Neoplasms; Electrophoresis, Polyacrylamide Gel; Epithelium; Humans; Keratins; Liver Neoplasms; Lymphatic Metastasis; Neoplasms; Peptides; Rectal Neoplasms; Respiratory Tract Neoplasms; Urinary Bladder Neoplasms