bromochloroacetic-acid and Hypopharyngeal-Neoplasms

We performed a prospective study to determine the cutoff value and the prognostic value of Cyfra 21-1, a serum tumor marker, in head and neck squamous cell carcinoma (HNSCC).. The serum concentration of Cyfra 21-1 was measured in a group of 300 patients (group 1) with HNSCC, in a control group of 71 healthy subjects (group 2), and in a group of 73 patients with a nonmalignant tumor or inflammatory disease (group 3). The concentrations were compared between the various groups and subgroups; the cutoff value was calculated with a receiver operating characteristic curve. Furthermore, the serum concentrations of Cyfra 21-1 before treatment in the group of 300 patients were compared with the stage of the disease and with the evolution of the overall survival rate and the disease-free survival rate. Finally, to determine whether Cyfra 21-1 is an independent prognostic factor, we compared the concentrations, by a Cox model, with the classic prognostic factors of HNSCC.. At the cutoff value of 1 ng/mL, the specificity was 94% and the sensitivity was 72%. The serum concentrations of Cyfra 21-1 were statistically correlated with the stage of the disease. The overall survival rate and the disease-free survival rate were lower in patients with high serum concentrations, and these differences were statistically significant (p < .001). The Cox model allows us to conclude that Cyfra 21-1 is a prognostic marker that is independent of other classic prognostic factors.. Cyfra 21-1 is an interesting tumor marker that could be proposed for the early detection of HNSCC with a cutoff value of 1 ng/mL. Furthermore, Cyfra 21-1 can be considered an independent prognostic marker.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Keratin-19; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Multivariate Analysis; Oropharyngeal Neoplasms; Prognosis; ROC Curve; Sensitivity and Specificity

To test laser scanning cytometry (LSC) for the analysis of ploidy in squamous cell carcinoma of the hypopharynx (SCCH) and to develop a routine application for minimal samples such as fine needle aspirate biopsies (FNABs).. From 11 individuals 30 FNABs of primary tumors (n=11) and lymphatic metastases of SCCH (n=11) and non-metastatic lymph nodes (n=8) are analyzed by LSC. This microscope based instrument scans the cells after immobilization on a glass slide and after double staining of cytokeratin and DNA. The location of each cell is stored with the fluorescence data. Therefore the morphology of every cell can be documented by re-staining with H & E; and re-localization on the slide. Additionally, aliquots are Feulgen-stained for image cytometry in 8 specimens.. The diploid reference peak is identified taking leukocytes as internal standard. The DNA-index of the carcinoma cells ranges from 0.4 to 3.8. Comparison with image cytometry shows good correlation (r=0.89).. LSC provides a reliable and objective way to determine the ploidy of SCCH pre-operatively. Colour figures can be viewed on http://www.esacp.org/acp/2003/25-2/gerstner.htm.

Topics: Biopsy; Biopsy, Fine-Needle; Carcinoma, Squamous Cell; Cell Separation; Eosinophils; Flow Cytometry; Humans; Hypopharyngeal Neoplasms; Keratins; Leukocytes; Lymph Nodes; Lymphatic Metastasis; Microscopy, Confocal; Ploidies; Rosaniline Dyes

Extravascular fibrin deposition is frequently observed within and around neoplastic tissue and has been implicated in various aspects of tumor growth. The distribution of fibrin deposits was investigated in squamous cell carcinomas representing different stages of tumor progression of the larynx (n = 25) and hypopharynx (n = 9) by immunofluorescent techniques. Double and treble labelings were used to detect fibrinogen and fibrin in combination with marker antigens for tumor cells (cytokeratin), endothelial cells (von Willebrand factor), macrophages (recognized by KiM7), as well as factor XIII subunit A (FXIIIA) and tenascin (an embryonic extracellular matrix protein newly expressed during tumorigenesis). All tissue samples showed specific staining for fibrinogen/fibrin. Fibrin deposition was localized almost exclusively in the connective tissue compartment of tumors with characteristic accumulation at the interface of connective tissue and the tumorous parenchyma. In certain tumor samples showing highly invasive characteristics, fibrin deposits were observed in close association with tumor blood vessels in the tumor cell nodules. The overlapping reactions with polyclonal antibody to fibrinogen/fibrin and monoclonal antibody to fibrin indicate the activation of the coagulation cascade resulting in in situ thrombin activation and fibrin formation. Fibrin was crosslinked and stabilized by FXIIIA as revealed by urea insolubility test. Accumulation of phagocytozing macrophages detected by Ki M7 monoclonal antibody could be seen in areas of fibrin deposition. The blood coagulation factor XIIIA was detected in and around the cells labeled with Ki M7 antibody. Tenascin and fibrin deposits were found in the same localization in the tumor stroma and in association with tumor blood vessels within the tumor cell nodules. Neither fibrin nor tenascin were detected in the histologically normal tissue adjacent to tumors. The close association between fibrin deposits and macrophage accumulation strongly suggests the active participation of tumor-associated macrophages in the formation of stabilized intratumoral fibrin that facilitates tumor matrix generation and tumor angiogenesis.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Disease Progression; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique, Indirect; Humans; Hypopharyngeal Neoplasms; Keratins; Laryngeal Neoplasms; Macrophages; Male; Middle Aged; Neoplasm Proteins; Tenascin; Thrombophilia; Transglutaminases

We reviewed the clinical records of 34 patients with laryngeal (25) and hypopharyngeal (9) spindle cell carcinomas who were treated at our institution between 1960 and 1990. All the spindle cell carcinomas were studied using paraffin section immunostains, and we performed ploidy analysis of the sarcomatoid component in 31 patients. Of the 31 patients who underwent their initial treatment at our institution, 25 were men and 6 were women (median age at presentation, 64.6 years). A T1 glottic tumor, usually seen as an exophytic firm mass, was the most common type of tumor observed (16 cases). The spindle cells were nondiploid in 86% of the carcinomas, with positive keratin immunostains in 74%. The median follow-up time was 3.7 years. Recurrence of the tumor after partial or total laryngectomy or pharyngectomy occurred in 10 patients. Eight patients died of their disease. The Kaplan-Meier estimate of surviving at least 3 years after initial treatment was 56.8%. Keratin positivity adversely affected the overall survival rate (p < 0.02). The survival rate of patients with hypopharyngeal tumors was worse than that of patients with laryngeal lesions (p < 0.001). The presence of keratin positivity and nondiploid DNA content in the spindle cell population supports the neoplastic epithelial origin of these tumors (sarcomatoid carcinoma). The overall tumor behavior and surgical therapy appeared to be comparable with those of squamous cell carcinomas at a similar stage.

Topics: Adult; Aged; Carcinoma; DNA, Neoplasm; Female; Humans; Hypopharyngeal Neoplasms; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Ploidies; Prognosis; Survival Analysis

Cytokeratin (CK) expression was studied in squamous cell carcinomas of different subsites in the head and neck by using cryostat sections from 27 head and neck squamous cell carcinomas (HNSCCs) and 6 cell lines established from HNSCC. All tissues were analyzed immunohistochemically with a panel of monospecific anti-keratin monoclonal antibodies. Most carcinomas recapitulated the expression pattern of keratins present in the basal layer of normal epithelium from the site of tumor origin. Regional differences in the expression of simple-epithelial type of keratins in stratified (pseudostratified) epithelia were to a large extent repeated in corresponding carcinomas. In the present study, localization of various keratins were surveyed and CK 18 specific monoclonal antibodies were specifically used to distinguish SCCs of the larynx or hypopharynx from SCCs of the oral cavity. CK 18 staining of almost all tumor cells was detected in 11 of 12 SCCs of the larynx and hypopharynx, but was only detected sporadically in 3 of 9 SCCs of the oral cavity. The present results show that CK 18 typing might be useful for distinguishing sites of origin of various HNSCCs. Findings also indicate that CK 18 expression in SCC might be modulated by microenvironmental factors.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Line; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Larynx; Mouth Mucosa; Mouth Neoplasms

Topics: Carcinoembryonic Antigen; Carcinoma; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Follow-Up Studies; Humans; Hypopharyngeal Neoplasms; Keratins; Laryngeal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Paget Disease, Extramammary; Penile Neoplasms; Skin Neoplasms

In order to obtain a more objective method to evaluate epithelial disorders and carcinomas of the hypopharynx, the expression pattern of cytokeratins (CKs) was investigated by ABC technique using several kinds of monoclonal antibodies that react monospecifically with each subclass of CKs. In normal epithelia, CK-19 was strongly positive in the basal layer but apparently reduced in suprabasal layers and completely negative in superficial layers, while CK-13 showed a striking contrast to CK-19, being expressed within the whole thickness of epithelia except only in the basal layer. These 2 subclasses were also observed in "abnormal" epithelia, and characteristic changes of their combination were demonstrated in proportion to the histological gradings. In invasive carcinomas, CK-19 was strongly positive in all carcinoma cells of poorly differentiated carcinomas. It was sporadically positive in moderately differentiated carcinomas, the more differentiated the more sporadic. It was completely negative in well differentiated carcinomas. CK-13, on the other hand, was negative in poorly differentiated carcinomas but positive in keratinized cells of moderately or well differentiated carcinomas. Strong expression of CK-1 was observed only in well keratinized cells of hyperkeratotic epithelia and well differentiated carcinomas. These characteristic findings are consistently observed in all samples and, then, may be useful in evaluating epithelial disorders and carcinomas of the hypopharynx, when used in conjunction with standard histological techniques. It seems most likely that these results play a part in investigating normal and abnormal processes of cell differentiation.

Topics: Carcinoma, Squamous Cell; Epithelium; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Immunohistochemistry; Keratins; Precancerous Conditions

Laminin biosynthesis was compared in four pairs of human squamous cell carcinoma cultures derived from primary and recurrent or metastatic tumors in four patients with cancer of the larynx and hypopharynx to determine if changes in laminin production accompany tumor progression. Laminin profiles of the malignant cells were compared with laminin biosynthesized by nonmalignant human keratinocytes. Pulse-chase biosynthetic labeling of the cultures with [35S]methionine established that all of the squamous carcinoma cell lines synthesize immunoreactive A (Mr 400,000), B1 (Mr 205,000), and B2 (Mr 200,000) laminin subunits; assemble them to form the intact laminin molecule (Mr 950,000); and secrete a portion of the laminin they produce into the culture media. One aspect of laminin expression unique to keratinocytes, both malignant and nonmalignant, was the occurrence of three additional glycoprotein forms (Mr 195,000, 170,000, and 160,000) in the laminin immunoprecipitates. In contrast to the laminin subunits, these glycoproteins were not immunoreactive with the anti-laminin antiserum on Western blots. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis without and with reduction of disulfide bonds revealed that the laminin immunoprecipitates contained a family of oligomeric molecules. These ranged in apparent molecular weight from 370,000 to 950,000 and were composed of laminin subunits and the glycoprotein forms linked by interchain disulfide bonds. The malignant keratinocyte cell lines from different patients were distinguishable in terms of the array of laminin and glycoprotein forms displayed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the rate of [35S]methionine incorporation into laminin during the pulse-labeling, the fraction of [35S]methionine-labeled laminin secreted into the medium during the chase incubation, and the absolute amount of laminin secreted into the culture medium as determined by enzyme-linked immunosorbent assay. However, cell lines established from primary and metastatic or recurrent cancer in the same patient were indistinguishable in their profile of laminin biosynthesis and secretion. In comparison to primary cultures of nonmalignant foreskin basal keratinocytes, the malignant cells secreted into the culture medium a larger fraction of the laminin that they produce. This is an indication that the malignant keratinocytes in culture deposited a less stable basal lamina-like extracellular matrix

Topics: Carcinoma, Squamous Cell; Cell Line; Choriocarcinoma; Electrophoresis, Polyacrylamide Gel; Epidermal Cells; Epidermis; Humans; Hypopharyngeal Neoplasms; Keratins; Laminin; Laryngeal Neoplasms; Molecular Weight

Different tumours of the head and neck were analysed by immunohistochemistry. The distribution pattern of several intermediate filaments was studied. Keratin filaments were typical of carcinomas, whereas vimentin filaments were typical of mesenchymal tumours of different origin. The advances of this new technique of "tumour typing" are discussed.

Topics: Carcinoma, Basal Cell; Cytoskeleton; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Lymphoma; Melanoma; Mouth Neoplasms; Nasopharyngeal Neoplasms; Neuroma, Acoustic; Oropharyngeal Neoplasms; Tonsillar Neoplasms; Vimentin