bromochloroacetic-acid and Laryngeal-Neoplasms

To review the clinical and pathological picture of laryngeal paragangliomas and compare laryngeal paragangliomas with the three other types of laryngeal neuroendocrine neoplasms.. The study presents a case review of a patient with a subglottic laryngeal paraganglioma treated at our institution, with a literature review of the laryngeal neuroendocrine neoplasms. Included is a review of all four neuroendocrine neoplasms, taking a close look at a comparison between laryngeal paragangliomas and atypical carcinoids tumors. All cases of subglottic laryngeal paragangliomas reported in the literature were also compiled and tabulated.. The patient's record was reviewed for age, symptomatology, workup, and surgical procedures performed.. The patient was disease free 36 months after undergoing a tracheostomy for airway control, followed by a cricoid split for complete excision of the tumor.. It is important to differentiate among the four laryngeal neuroendocrine neoplasms, especially between atypical carcinoids and paragangliomas. Each tumor requires different treatments, with the former requiring a more aggressive approach. Paragangliomas must be completely excised to prevent their recurrence, and this approach should be considered a curative treatment. In addition, the immunohistochemical battery is of paramount importance in obtaining the correct pathological diagnosis.

Topics: Aged; Calcitonin; Carcinoma, Neuroendocrine; Endoscopy; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Paraganglioma; Tracheal Neoplasms; Tracheostomy

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

Carcinoid neoplasms, although rare, have to be considered in the differential diagnosis of neoplasms of the larynx. The total number of cases reviewed and listed in the present article is 47. The gross appearance of carcinoid tumours is not characteristic and does not differ from that of other malignant neoplasms of the larynx. Under the light microscope various types can be distinguished, which are described and illustrated in this review article. Available material of five previously published cases and of one new case have been re-examined under the electron microscope and by modern histochemical and immunohistochemical methods. The ultrastructural presence of neurosecretory granules and of argyrophilia by the Grimelius technique were uniformly positive, together with monoclonal antibodies for somatostatin and keratin. These special methods offer a reliable basis for the diagnosis of neuroendocrine neoplasms to which carcinoid tumours belong. The treatment of carcinoid neoplasms of the larynx is surgical.

Topics: Adult; Aged; Aged, 80 and over; Carcinoid Tumor; Carcinoma, Squamous Cell; Cytoplasmic Granules; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Somatostatin

Ten cell lines established from surgical specimens of human squamous carcinomas of the tongue and larynx have been investigated with respect to their motility, ultrastructure, karyotypes, certain biochemical features, interaction with normal epithelial and stromal elements and capacity to infiltrate three-dimensional organoid systems. All the cell lines have maintained several morphological and biochemical characteristics indicating a common origin, although the extent to which each line displays this heritage is variable. The phenotypes of each of the individual cell lines are, however, notably stable. Data are provided for epithelial surface markers (including epidermal growth factor, EGF) and for the synthesis and release of prostaglandins and proteases which may be involved in invasive mechanisms. Encounters between the cell lines and organoid substrata (embryonic chick heart spheroids, human amnion, chick chorioallantoic membrane) are described: the results indicate a scale of invasiveness ranging from lack of penetration to full-thickness infiltration by cells showing various distinctive growth patterns. Correlation between in vitro and in vivo findings is discussed, and it is suggested that the biological heterogeneity of the lines may reflect inherent properties of the original carcinoma cell populations which are more distinctly expressed in vitro.

Topics: Aged; Animals; Bone and Bones; Calcium-Binding Proteins; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cartilage; Cell Communication; Cell Line; Cell Movement; Chick Embryo; Epidermal Growth Factor; Female; Humans; Karyotyping; Keratins; Laryngeal Neoplasms; Male; Membrane Proteins; Microscopy, Electron; Middle Aged; Mucin-1; Tongue Neoplasms

Papillomaviruses induce tumors of keratinocytes. Vegetative viral DNA replication and virion assembly are seen in those cells which are in the process of keratinizing or are keratinized. To date, no cell culture system has been developed that permits expression of the complete viral life cycle. Keratinocytes infected in culture may harbor the virus as a stable, replicating episome, but they do not support vegetative viral growth, nor do they become immortalized or transformed. The major obstacle in using keratinocyte cultures may be related to a dual need for transformation and full differentiation. Some animal papillomaviruses have been shown to be capable of transforming cultured murine fibroblasts. The fibroblast model is useful for identifying the viral-transforming gene(s) and their products.

Topics: Animals; Cattle; Cell Line; Cell Transformation, Viral; DNA Replication; Epidermal Cells; Epidermis; Fibroblasts; Humans; Keratins; Laryngeal Neoplasms; Mice; Papilloma; Papillomaviridae; Rabbits; Virus Cultivation; Virus Replication

Topics: Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Humans; Keratins; Laryngeal Neoplasms

The objective of this study is to evaluate the incidence of occult nodal micrometastases in N0 laryngeal squamous cell carcinoma using cytokeratin immunohistochemical analysis (CKIHA) and its influence on the overall occult metastatic rate. This is a prospective cohort study. A total number of 30 patients with N0 stage laryngeal cancer underwent 46 selective neck dissections for elective treatment of the neck. Nodes found to be negative using routine histopathological examination were evaluated for the presence of micrometastasis using CKIHA. The occult micrometastasis rate for all cases was 26.7 % which significantly increased the overall occult metastasis rate to 50 % (P = 0.014). The micrometastasis rate was 30.8, 25 and 20 % for glottic, supraglottic and transglottic tumors, respectively, which increased the overall occult metastasis rate to 53.8, 50 and 40 % but without statistical impact. The micrometastasis rate was 35.7 and 23.1 % in T3 and T4 tumors, respectively, and this increased the overall occult metastasis rate to 50 and 61.5 % with statistical influence in T3 tumors (P = 0.046). Micrometastasis upstaged the neck in 7 (23.3 %) patients with statistical impact on the PN stage (P = 0.007). The overall occult nodal metastasis rate in N0 laryngeal cancer is underestimated. Nodal micrometastasis may be missed during routine histopathological examination and can be detected using CKIHA.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cohort Studies; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neck Dissection; Neoplasm Micrometastasis; Neoplasm Staging; Prospective Studies; Sensitivity and Specificity; Squamous Cell Carcinoma of Head and Neck

To determine the feasibility of viable storage of head and neck squamous cell carcinoma (HNSCC) for regrowth of cells in culture.. Laboratory-based translational study.. Methods for intermediate-term frozen storage of viable HNSCC were explored using small pieces of primary tumor and dissociated HNSCC cells after short-term culture. Viable cells after freezing were confirmed by adherence to tissue culture plates, cell morphology, and increased cell or colony density. Two cultures were immunostained for cytokeratin to confirm epithelial origin of viable cultured cells after freezing.. Six primary HNSCCs (two oral cavity, three larynx, one oropharynx) and two HNSCCs that had been passaged through a xenograft (two oral cavity) were dissociated to single cells and grown in short-term cell culture for 0 to 12 passages. After short-term culture, cells were frozen for up to 8 months, thawed, and replated. Frozen cells derived from all tumors (six primary and two xenografts) were successfully replated with cultures lasting >7 days with seven of eight tumors presenting increased colony or cell density over 1 week of growth after freezing. In total, 15 of 15 tested samples derived from six primary and two xenografted HNSCCs were viable after freezing.. In the current study, we show that biopreservation of primary or xenografted HNSCC using short-term cell culture is feasible. Initial short-term cell culture was required for successful storage and viability of frozen cells. These proof-of-principle studies, if more widely implemented, could improve preclinical testing of new therapies for HNSCC.

Topics: Carcinoma, Squamous Cell; Cryopreservation; Feasibility Studies; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Tissue Banks; Transplantation, Heterologous; Tumor Cells, Cultured

The clinical relevance of the carbohydrate antigen Sialyl Lewis a (SLea) as a serum tumor marker in diagnosis and follow-up treatment is unquestioned in a broad spectra of human carcinomas. Overexpression of this antigen is combined with poor prognosis and malignant relapse. The aim of our study was the systematic investigation of SLea expression in squamous cell carcinoma of the larynx versus normal and phlogistic tissue.. Paraffin-embedded sections of normal, phlogistic and squamous cell carcinoma tissue were incubated with a monoclonal antibody against SLea. The staining reaction was performed using ABC-Peroxidase and DAB. As a positive control tissue of breast cancer was used and the negative control was performed with unspecific mouse IgM. Semiquantitative evaluations were carried out double-blinded by two independent investigators, including a pathologist.. A very faint expression of SLea (Ca19-9) in normal laryngeal tissue, a moderate upregulation in phlogistic tissue and a dramatic upregulation in some types of squamous cell carcinoma of the larynx were observed. Laryngeal cancer is the most common cancer of the upper aerodigestive tract. Most cases of laryngeal cancer are squamous cell carcinoma and can be classified into: well differentiated (more than 75% keratinization), moderately differentiated (25-75% keratinization), and poorly differentiated (<25% keratinisation) carcinomas.. The results of this study indicate that SLea is a potential tumor marker in carcinoma of the larynx.

Topics: Biomarkers, Tumor; CA-19-9 Antigen; Carbohydrates; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lewis X Antigen; Sialyl Lewis X Antigen; Up-Regulation

Occult foci of neoplasm cells in lymph nodes (referred to as micrometastases) in various squamous cell carcinomas may be discovered by immunohistochemistry by using anti-CKs (cytokeratine filaments) policlonal antibodies which reactive with epithelial cells. Matrix metalloproteinases (MMPs) are proteolytic family enzymes represent a group of endopeptidases which are capable to degrading components of the extracellular matrix and have been implicated as playing an important role in cancer invasion and metastases. The purpose of this study was to analyze the morphological parameters and to investigate MT1-MMP expression in laryngeal carcinoma to relate the expression to CKs in pN0 lymph nodes.. To presented the direct correlation between the morphological features of tumor front and the probability of micrometastases and prediction of prognosis we have analyzed 22 patients operated for squamous cell carcinoma of the larynx. The total score of TFG classification, tumor clinicomorphological features and grade of matrix metalloproteinase membrane type 1 staining in tumor front were analyzed to predict the presence of micrometastases and prognosis. Immunohistochemical methods with a panel of CKs antigens in lymph nodes and MT1-MMP expression in tumor tissue were performed.. Our study showed that the total morphologic score TFG is very useful in the prediction of micrometastases in patients with laryngeal squamous cell carcinoma. The statistical analysis has revealed a significant correlation between the total TFG score and the depth of invasion and the presence of micrometastases. Positive MT1-MMP expression in 68.2% cases was observed. There was no significant relationship for immunoexpression of MT1-MMP in examined group of patients with advanced laryngeal carcinoma and positive poliCKs stain in lymph nodes.. The results of study suggest that extended traditional pathologic evaluation by features from the TFG classification, especially the depth of invasion, could aid in diagnosis of micrometastases. The positive expression of poliCKs in the conventional pathological examination of pN0 lymph nodes appears to play an important role in determining prognosis in patients with carcinoma of the larynx.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymphatic Metastasis; Male; Matrix Metalloproteinase 1; Middle Aged; Neoplasm Staging; Prognosis

Lymph nodes estimated as pNO in conventional morphological studies could have focuses of carcinoma cells with a diameter of < or =2 mm referred to as micrometastases (pN+). Matrix metalloproteinases (MMPs) are proteolytic family of endopeptidases which are capable to degrading components of the extracellular matrix and play an important role in cancer invasion and metastases. The aim of this study was to investigate MT1-MMP expression in carcinoma of the larynx and analyze morphological parameters to relate the expression to CKs in pN0 lymph nodes.. To presented the direct correlation between 6 morphological features of tumor front and the probability of micrometastases and prediction of prognosis 22 patients operated for squamous cell carcinoma of the larynx were analyzed. The total score of TFG, chosen clinicomorphological features and grade of matrix metalloproteinase membrane type 1 staining in tumor front were analyzed to predict the presence of micrometastases and prognosis. Immunohistochemical methods with a panel of CKs antigens in lymph nodes and MT1-MMP expression in tumor tissue were per-lymph nodes. There was no significant relationship for immunoexpression of MT1-MMP and positive poliCKs stain.. The results of study suggest that extended traditional pathologic evaluation by features from the TFG classification could aid in diagnosis of micrometastases. The positive expression of poliCKs in the pN0 lymph nodes appears to play an important role in determining prognosis in patients with carcinoma of the larynx.

Topics: Aged; Carcinoma; Carcinoma, Squamous Cell; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Matrix Metalloproteinase 14; Middle Aged; Prognosis

Topics: Actinomycosis; Aged; Carcinoma; Humans; Immunohistochemistry; Keratins; Laryngeal Diseases; Laryngeal Neoplasms; Male; Tracheal Diseases

Topics: Aged; Biomarkers, Tumor; Carcinoma; Desmin; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Vimentin

To analyze the lymphatic distribution of metastatic carcinomatous cells in cervical lymph nodes in head and neck squamous cell carcinoma (HNSCC).. We retrospectively reviewed 119 patients treated in our hospital for HNSCC (1999-2004). Topography of the neck dissection specimens was prospectively classified according to the classification of Robbins. The 4000 lymph nodes were analyzed by optical microscopy using hematoxylin-eosin-safran (HES) staining. In cases of negative results in level II, cytokeratin (AE1/AE3) immunodetection was performed.. Metastases were visualized using HES in 6.4% of lymph nodes for oral cavity, and 4.7% of oropharyngeal, 4.4% of hypopharyngeal, and 1.3% of endolaryngeal cancers. The highest incidence of nodal metastasis was observed in level IIa (P < 0.01). In eight patients (6.7%) with lymph node metastases, level II was spared. In these patients, all 134 nodes histologically negative on HES were confirmed to be negative by IHC.. Level IIa is the main level involved in regional metastases of HNSCC, regardless of the primary site of cancer. However, in eight (6.7%) patients, level II was spared, as confirmed by IHC. In these cases, level II did not represent the first step of drainage from the tumor. The sentinel lymph node technique in HNSCC is discussed in light of these results.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Coloring Agents; Female; Fluorescent Dyes; Head and Neck Neoplasms; Humans; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck; Neck Dissection; Neoplasm Staging; Pharyngeal Neoplasms; Prospective Studies; Retrospective Studies; Sentinel Lymph Node Biopsy

Lymph node micrometastases in patients with squamous cell carcinoma of the larynx found node-negative by conventional histology may be discovered by immunohistochemistry, particularly by using mono- and policlonal antibodies which are reactive with epithelial cells. Then tumors classified as pN0 by routine methods may be reclassified more correctly as pN1. Authors investigated the incidence of micrometastases in the neck dissection specimens originally staged as pN0 from 22 patients with laryngeal cancer treated surgically at ENT Department Medical University of Lodz between 1998-1999 according to: the survival, using immunostaining with panel of mono- and policlonal antibodies to cytokeratins CK1, CK4, CK5, CK6, CK8, CK10, CK13 and CK18. The relationship between micro-metastases and clinical features of primary tumor and lymph nodes has been discussed.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Survival Rate

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

According to the recent reports analyses of characteristic of neoplasm's invasion is one of the most reliable methods of estimation the progress of the changes of tumor and prediction the outcome in patients with laryngeal cancer. Depth and mode of invasion are features which are able to assess the dynamics of the tumor growth quite precisely. In this study it was presented direct relation between morphological features of tumor front as a depth and mode of carcinoma's growth and the probability of micrometastases. The authors have analysed 22 cases of patients who were operated on the laryngeal squamous cell carcinoma in ENT Department Medical University of Lodz in the period of 1998-1999. Features of the TFG and its dependence on lymph node micrometastases, considered in immunohistochemistry with using of panel of cytokeratins (CKs) were analysed. Our study showed that feature such as depth and mode of invasion is very useful in prediction of micrometastases in patients with laryngeal squamous cell carcinoma.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Predictive Value of Tests; Prognosis; Retrospective Studies

In patients treated surgically due to neoplasm, in lymph nodes can be presented micrometastases, focuses 1-2 mm of carcinoma's cells. Lymph node micrometastases in patients with squamous cell carcinoma of the larynx found node-negative by conventional histology may be discovered by immunohistochemistry, particularly by using antibodies which are reactive with epithelial cells eg. cytokeratin antigens. Then tumors classified as pN0 by routine methods could be reclassified more correctly as pN1. Authors investigated the incidence of micrometastases in the neck dissection specimens originally staged as pN0 from 22 patients with laryngeal cancer treated surgically at ENT Department Medical University of Lodz between 1998-1999, according to the survival, using immunostaining with panel of polyclonal antibodies to cytokeratins. The relationship between micrometastases and clinical (pre- and intraoperative) features of lymph nodes were estimated.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Prognosis; Retrospective Studies

Despite innumerous both therapeutic and histopathologic studies that have been performed no morphologic markers are currently available in order to predict the outcome in patients with laryngeal cancer. According to the recent reports tumor front grading (TFG) is one of the most reliable methods of estimation of the progress of the changes in the peripheral part of tumor. TFG seems to be one of the technics, which is able to assess the dynamics of the tumor growth quite precisely. In this study it was presented direct relation between morphological features of tumor front and the probability of micrometastases. The authors have analysed 22 cases of patients who were operated on the laryngeal squamous cell carcinoma in ENT Department Medical University of Lódź in the period of 1998-1999. Features of the TFG and its dependence on lymph node micrometastases, considered in immunohistochemistry with using of panel of cytokeratins (CKs) were analysed. Our study showed that feature such as TFG is very useful in prediction of micrometastases in patients with laryngeal squamous cell carcinoma. The statistical analysis showed significant correlation between TFG score and mode of invasion and depth of invasion. The presented study emphasizes that it is necessary to extend the traditional histopathological diagnosis by TFG, which might influence decisions regarding therapeutic management and could eventually lead to more appropriate and individualized therapy.

Topics: Aged; Aged, 80 and over; Antigens; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Prognosis

The diagnostic sensitivity and specificity of tumor markers in head and neck cancers is not satisfactory. It is a stimulus for search of other biochemical indicators, among others determinations of acute phase proteins, helpful in head and neck cancers diagnostics and prognosis. In a group of 33 patients with squamous cell carcinoma of the pharynx and larynx (T1-4 N0-3 M0) CYFRA 21-1, SCC-Ag and acute phase proteins such as prealbumin, albumin, alpha-1 acid glycoprotein, alpha-1 antytrypsin, transferrin, ceruloplasmin and C-reactive protein (CRP) determinations were performed before radiotherapy. Significantly greater area under ROC curve for CYFRA 21-1 than for SCC-Ag was found. In T3-4 group, significantly lower albumin and higher AAG and CRP concentrations in comparison with T1-2 patients were observed. Multivariate analysis revealed that apart from tumor stage, elevated concentrations of SCC-Ag and/or CRP are independent unfavorable prognostic factors.

Topics: Acute-Phase Proteins; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Keratin-19; Keratins; Laryngeal Neoplasms; Multivariate Analysis; Pharyngeal Neoplasms; Prognosis; ROC Curve; Sensitivity and Specificity; Serpins; Time Factors; Treatment Outcome

To assess cytokeratin-17 (CK17) as an immunohistochemical marker for squamous cell carcinoma of the larynx, we stained 63 tissue samples from 63 consecutive patients who were believed or suspected to have squamous cell carcinoma of the larynx for CK17 and analyzed them by computerized histomorphometry. The mean staining intensity for CK17 was significantly stronger (p < .01) in cancerous cells, dysplasia, and normal epithelium proximal to the tumor than in distal normal epithelium and polyps. The percentage of stained area, within samples taken from a single patient, was significantly higher in malignancy and dysplasia as compared to distal normal epithelium and in malignancy as compared to dysplasia and proximal normal epithelium (p < .001). The integrated optical density was significantly higher in the malignant epithelium, dysplasia, polyps, and proximal normal epithelium than in distal normal epithelium (p < .0001). We conclude that CK17 is a highly sensitive and specific immunohistochemical marker for premalignant and malignant transformation in the larynx. Further investigation is warranted in order to assess the role of CK17 in determining safe resection borders.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Proteins; ROC Curve; Sensitivity and Specificity

The aim of this study was to determine the occult lymph node metastasis rates with immunoperoxidase staining for cytokeratin in supraglottic larynx cancers and to assess our approach to the neck.. Twenty-two patients who had squamous cell carcinoma in the supraglottic region and no histopathologic metastasis in the neck who had their cancer detected with the use of hematoxylin-eosin were included in the study. All of the specimens were reevaluated with the use of immunoperoxidase staining for cytokeratin.. Micrometastatic disease (pN1) has been detected in 3 patients (13.61%) in whom no metastasis was detected with routine histopathologic examination.. Results suggest that the occult metastasis rates are higher than those detected with routine hematoxylin-eosin staining. However, because it is accepted that neck dissection alone has adequate therapeutic efficiency in pN1 patients, the detected 13.61% rate of micrometastases has not changed our treatment plan in the neck.

Topics: Carcinoma, Squamous Cell; Eosine Yellowish-(YS); Fluorescent Dyes; Glottis; Hematoxylin; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Lymph Node Excision; Lymphatic Metastasis

The frequency of amyloid deposits associated with squamous cell carcinoma (SCC) and dysplasia in the oral cavity, pharynx and larynx was examined. In addition, the origin of amyloid proteins by immunohistochemical staining with a panel of anticytokeratin monoclonal antibodies was investigated. Amyloid deposits were found in eight of 73 (11.0%) SCC and one of seven (14.3%) dysplasias in the oral cavity, in eight of 22 (36.4%) SCC and zero of two (0%) dysplasias in the pharynx, and in 22 of 37 (59.5%) SCC and four of 10 (40.0%) dysplasias in the larynx. Eight of 12 different cytokeratin (CK) antibodies reacted with these deposits: 34 beta E12 (CK1, -5, -10, -14) reacted with amyloid deposits in 19 of 19 cases (100%), LL002 (CK14) in eight of 18 cases (44.4%), MNF116 (CK5, -6, -8, -17) in eight of 19 cases (42.1%), D5/16B4 (CK5, -6) in five of 18 cases (27.8%), DE-K10 (CK10) in four of 17 cases (23.5%), RCK108 (CK19) in three of 18 cases (16.7%), 34 beta B4 (CK1) in three of 19 cases (15.8%) and AE8 (CK13) in two of 17 cases (11.8%). These antibodies always reacted with the cytoplasm of squamous cell lesions. Amyloid deposits in two cases contained a CK5 and CK14 pair, and in another two cases they contained both a CK5 and CK14 pair, and a CK1 and CK10 pair. Anti-CK antibodies, including OV-TL12/30 (CK7), c-51 (CK8), DC10 (CK18) and IT-Ks20.8 (CK20) did not react with the amyloid deposits. We conclude that the amyloid deposits associated with SCC or dysplasia in the oral cavity, pharynx or larynx were derived from CK of cancer cells and that some amyloid deposits might be assembled by two or more different CK.

Topics: Adult; Aged; Aged, 80 and over; Amyloid; Amyloidosis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Pharyngeal Neoplasms; Precancerous Conditions

Serologic tumor markers are actually a valuable tool for diagnosis, management and follow up in some cancer types. The concentrations of Cyfra 21.1, SCC and TPS has been analysed in several groups of head and neck tumors, but exclusively in larynx there are no studies concerning this subject.. The purpose of the present study was to assess the expression of serum fragments of cytokeratins (CK's) 18/19, and squamous cell carcinoma antigen (SCCA) in a same group of patients with squamous cell carcinoma of larynx, and correlate the results with tumor localisation, T, stage, histology, presence of regional metastasis, and smoking habits.. Forty six patients treated at the Department of Otorhinolaryngology, Porto Center of the Portuguese Institute of Oncology were enrolled in the study. Blood samples were obtained before treatment, and determinations effectuated using standard commercial available kits.. Although serum concentrations of Cyfra 21.1, TPS and SCC were not significantly elevated in patients with laryngeal cancer, more expressive levels namely for TPS were observed in advanced supraglotic and metastasis tumors independent of the differentiation degree.

Topics: Antigens, Neoplasm; Carcinoma, Squamous Cell; Female; Humans; Keratin-19; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Peptides; Serpins

Cytokeratins (CKs) are a subgroup of intermediate filament proteins that take part in forming the cytoskeleton. The epithelial cells in different organs express distinct CKs, and this expression may be modified during malignant transformation. Here we describe the use of reverse transcriptase-polymerase chain reaction followed by Southern blotting to determine the profile of expression of CKs in both normal and malignant laryngeal samples. Thirty-six samples were subjected to histologic examination and classified as 17 squamous cell carcinomas, 3 dysplastic lesions, and 16 normal samples. CK8 and CK19 were expressed in almost all samples, both cancerous and normal, and were therefore used to verify the integrity of RNA. Expression of CK2, CK9, and CK20 was not detected in any of the samples, normal or cancerous. CK15 and CK18 showed low sensitivity for detection of cancer (36.4% and 45.5%, respectively). CK10 showed relatively high sensitivity (91%), but only moderate specificity (69.2%). Only CK17 showed both high sensitivity and specificity (91% and 92.3%, respectively; positive predictive value, 91%). We propose that CK17 may be considered a promising candidate to use as a molecular marker for malignant transformation in laryngeal squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Blotting, Southern; Carcinoma, Squamous Cell; Female; Humans; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction

In order to investigate the role of Cytokeratin 13(CK13) gene in laryngeal carcinogenesis, we detected the deletion of CK13 gene through LOH analysis indirectly at DNA level using 5 STR primers within and near CK13 gene in 72 cases of laryngeal squamous cell carcinoma, then detected the differential expression between 16 cases of paired normal and cancerous tissue by Northern blot, and performed immunohistochemistry using well characterized monoclonal antibody against CK13 in squamous cell carcinoma of different stages. We found that all of the microsatellite loci exist LOH, and the LOH frequencies were 18.03%, 28.13%, 27.42%, 39.68% and 34.85% at D17S1964E, D17S2092, D17S791, D17S1665 and D17S808 respectively. The LOH+ cases accounted for 77.78% (56/72), and the frequencies of LOH were not related to the type of laryngeal carcinoma and the lymphoid metastasis; but significantly related to the differentiation, P < 0.05. CK13 gene is expressed significantly higher in 16 cases of normal tissues than in paired cancerous tissues, and the immunostain revealed that CK13 was expressed in normal laryngeal squamous cell or high differentiation stage, and its expression decreased or disappeared in poor ones, P < 0.01. CK13 gene might play an important role in the laryngeal carcinogenesis, acting as a novel tumor suppressor gene, and may be relevant to laryngeal squamous cell carcinoma diagnosis and prognosis. Further research will contribute to conform it.

Topics: Carcinoma, Squamous Cell; Chromosomes, Human, Pair 17; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Loss of Heterozygosity; Microsatellite Repeats; Neoplasm Staging

Two new cell lines, designated as RK-33 and RK-45, have been successfully established by an outgrowth technique from two different larynx tumours obtained from patients after laryngectomy. Both cell lineshave been maintained incultureforover 18 monthsandrecently have reached passage number 220 (RK-33) and 110 (RK-45). The cells display an epithelial morphology and multiply with a population doubling time of about 24 h (RK-33) and about 40 h (RK-45). The epithelial nature of the cells was also confirmed by expression of cytokeratins 8 and 18. Both lines were sensitive to antiproliferative effect of the tested cytostatic agents such as methotrexate. etoposide and thiotepa, with methotrexate being the most effective. We believe that both cell lines: RK-33 and RK-45 could be a suitable model for studying larynx cancer biology, however, further characterization of their properties is needed.

Topics: Antineoplastic Agents; Blotting, Western; Carcinoma; Cell Division; Cell Line; Female; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged

Expression of glycan determinants for in situ binding is the prerequisite for a productive protein (lectin)-carbohydrate recognition. Labeled tissue lectins as tools are preferable to plant lectins to assess this parameter, because plant and animal lectins with identical saccharide specification can well differ in their profiles of oligosaccharide binding pattern. Due to their relevance in growth control and matrix adhesion the family of galectins (galactoside-binding metal ion independent animal lectins) is receiving increasing utilization in human biology. Employing biotinylated galectin-1 and galectin-3 we studied the expression of binding sites for these galectins in normal human squamous epithelium and human carcinomas from the oropharyngeal region and larynx in relation to the expression of LP-34+ cytokeratins by the procedure of double labeling. Tissue sites accessible for galectin-1 were located in all layers of normal epithelium and in tumor cells. In contrast, galectin-3 binding was suprabasal in the normal epithelium and in tumor cells exhibiting signs of keratinization. These results reveal differences in the localization of accessible sites for the two galectins. Relating to cell development galectin-3 appeared to display affinity to areas with increased extent of differentiation.

Topics: Antigens, Differentiation; Carcinoma, Squamous Cell; Cell Differentiation; Fluorescent Antibody Technique, Indirect; Galactosides; Galectin 1; Galectin 3; Hemagglutinins; Humans; Keratins; Laryngeal Neoplasms; Lectins; Oropharyngeal Neoplasms

Phenotypic changes resembling an epithelial-to-mesenchymal transition often occur as epithelial cells become tumorigenic. Two proteins that have been implicated in this process are vimentin and N-cadherin. In this study, we sought to establish a link between expression of vimentin and N-cadherin as oral squamous epithelial cells undergo a morphologic change resembling an epithelial-to-mesenchymal transition. We found that N-cadherin and vimentin did not influence the expression of one another.

Topics: Animals; Cadherins; Carcinoma, Squamous Cell; Cell Adhesion; Clone Cells; Humans; Keratins; Laryngeal Neoplasms; Mice; Phenotype; Recombinant Proteins; Transfection; Tumor Cells, Cultured; Vimentin

We investigated by immunocytochemistry the expression of the Ca(2+) binding protein S100A2 in 62 cases of laryngeal squamous-cell carcinoma (SCC). S100A2 was detected in 18/19 (95%) low-grade tumors and in 22/43 (51%) high-grade tumors, which were partially keratinizing. The remaining 21/43 (49%) high-grade tumors were non-keratinizing, anaplastic tumors and clearly S100A2-negative. In normal laryngeal squamous epithelium and in laryngeal SCC, S100A2 expression was strictly associated with that of cytokeratins 14 (P = 0.0002) and 17 (P = 0.0021), suggesting an association of S100A2 expression and cell commitment to squamous differentiation. A correlation was found between S100A2 tumor positivity and longer relapse-free (P = 0.0005) and overall (P = 0.0095) survival.

Topics: Analysis of Variance; Biomarkers, Tumor; Calcium-Binding Proteins; Carcinoma, Squamous Cell; Chemotactic Factors; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; S100 Proteins; Survival Analysis

Topics: Carcinoma, Squamous Cell; Humans; Keratins; Laryngeal Neoplasms; Neoplasm Staging

We used differential display to detect enhanced expression of an mRNA fragment encoding cytokeratin 17 (Ck-17) in respiratory syncytial virus (RSV)-infected epithelial cells. Expression increased 12-fold by 96 h after infection but remained unchanged in cells challenged with virus in the presence of neutralizing anti-RSV fusion protein antibody. Immunoblots of RSV-infected cell lysates probed with an anti-keratin antibody demonstrated stable expression of total cytokeratins over time. When probed with an anti-Ck-17 monoclonal antibody, Ck-17 was first detected at 4 days after infection. In situ staining demonstrated that Ck-17 expression localized to regions of syncytia formation. Expression of Ck-17 mRNA also increased in response to intracellular RSV-F protein in the absence of active RSV infection. No increase in Ck-17 mRNA expression and no syncytia were observed in RSV-infected cells grown in the presence of the NF-kappaB inhibitor gliotoxin. These results suggest that RSV-induced transcriptional activation of the Ck-17 gene is dependent on an NF-kappaB-associated signaling pathway.

Topics: Adenoids; Cells, Cultured; Epithelial Cells; Gene Expression Regulation; Giant Cells; Gliotoxin; Humans; Keratins; Laryngeal Neoplasms; NF-kappa B; Recombinant Proteins; Respiratory Syncytial Viruses; Transfection; Tumor Cells, Cultured

To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly-used model of intraepithelial neoplasia in the cervix.. Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion).. Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semiobjective methods of quantitative morphometry and immunohistochemistry.

Topics: Epithelium; Humans; Hyperplasia; Keratins; Laryngeal Diseases; Laryngeal Mucosa; Laryngeal Neoplasms; Multicenter Studies as Topic; Precancerous Conditions; Slovenia

This study is designed to assess gene expression of squamous cell carcinoma antigen (SCCA) mRNA to detect micrometastases in cervical lymph nodes (LNs) of head and neck cancer. We examined the expression of SCCA mRNA in 12 primary tumors and 212 cervical LNs (101 LNs taken from 8 patients with tongue cancer, 71 from 7 patients with gingival cancer, 19 from 2 patients with laryngeal cancer, 9 from 2 patients with pharyngeal cancer, 7 from 1 patient with cancer of the buccal mucosa, and 5 from 1 patient with cancer of floor of the mouth). Detectability of metastatic LNs by nested and single reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with semiserial sections (hematoxylin-eosin staining and keratin immunostaining). All primary tumors expressed SCCA mRNA. Of 198 histologically metastasis-negative nodes, SCCA mRNA was detected in 37 (18.7%) by nested PCR. Eleven micrometastatic foci in 9 LNs (4.6%) were discovered by semiserial sectioning. This suggests that SCCA mRNA is a promising tumor marker for detecting the micrometastases in cervical LNs of head and neck cancer.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; False Negative Reactions; Gingival Neoplasms; Head and Neck Neoplasms; Humans; Keratins; Laryngeal Neoplasms; Lymphatic Metastasis; Microtomy; Mouth Mucosa; Neck; Neoplasm Proteins; Pharyngeal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Serpins; Staining and Labeling; Tongue Neoplasms

This report describes a case of atypical carcinoid of the larynx with metastatic tumor to cervical lymph nodes showing features similar to paraganglioma. Immunohistochemically, both the primary and metastatic tumor were positive for epithelial membrane antigen, cytokeratin, neuron-specific enolase, chromogranin, synaptophysin, calcitonin and carcinoembryonic antigen. The sustentacular cells in pseudo-cell ball ("Zellballen") formations were shown by a positive S-100 marker. Electron microscopic analysis revealed numerous neuroendocrine granules measuring 150-250 nm in diameter. Clinical features, histological appearance, histochemical, immunohistochemical and ultrastructural findings, as well as differential diagnosis are discussed.

Topics: Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoid Tumor; Chromogranins; Cytoplasmic Granules; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymphatic Metastasis; Male; Microscopy, Electron; Mucin-1; Neck; Paraganglioma; Phosphopyruvate Hydratase; S100 Proteins; Synaptophysin

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

Undifferentiated nasopharyngeal carcinomas are universally associated with Epstein-Barr virus (EBV). This association has been exclusively established in lymphoepithelioma-like carcinomas in some locations. The relationship between EBV and lymphoepithelioma-like carcinomas in the larynx is unknown. In none of the few laryngeal lymphoepithelioma-like carcinomas reported have EBV investigations been carried out. We present here two supraglottic laryngeal lymphoepithelioma-like carcinomas in which EBV antigens were not demonstrable using immunohistochemical and molecular methods. Our results suggest that EBV may not be involved in laryngeal lymphoepithelioma-like carcinoma at least in Western patients.

Topics: B-Lymphocytes; Carcinoma; Epiglottis; Herpesvirus 4, Human; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Plasma Cells; Polymerase Chain Reaction; Retrospective Studies; RNA, Viral; T-Lymphocytes; Tumor Suppressor Protein p53

Spindle cell carcinoma (SpCC) is uncommon, with a predilection for the upper aerodigestive tract. Its histogenesis has not been resolved, although most authors support the sarcomatoid carcinoma concept. Ploidy analysis and proliferation indices have not been reported for laryngeal SpCCs. The authors examined the pathological and clinical features of 26 patients (25 men, 1 woman; mean age, 64 years) with laryngeal SpCC treated at the Mayo Clinic from 1960 to 1990. Twenty-three tumors were examined with digital image analysis for DNA content of the spindle cell population (13 tumors had a sufficient squamous component to be analyzed separately). The glottis was involved most frequently (19 patients); 21 tumors were grossly polypoid. Twenty-three tumors were biphasic, and three were monophasic. Overall, 17 tumors (65%) showed keratin positivity in the spindle cell component. Polyclonal antikeratin (15 positive cases), 34betaE12 (15 positive), and AE1/AE3 (12 positive) were the most sensitive markers. Spindle cells were diploid in 5 tumors (22%) and nondiploid in 18 (78%); conventional squamous cell carcinoma was diploid in 4 cases and nondiploid in 9. DNA ploidy results were concordant between the two populations in 11 of 13 tumors (85%). Mean percent MIB-1 staining was 31% in the sarcomatoid component and 45% in the squamous component. In our primary treatment group of 22 patients (median follow-up, 6.4 years), 4 (18%) had local recurrence, 3 (14%) had distant metastasis, and 4 (18%) died of disease. Presence of a nondiploid spindle cell population in 78% of cases of laryngeal SpCC is interpreted as evidence of a neoplastic rather than reactive process. Keratin positivity in nearly two thirds of tumors supports the theory of epithelial origin of these tumors (sarcomatoid carcinoma).

Topics: Adult; Aged; Aneuploidy; Biomarkers; Carcinoma; Cell Division; DNA, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Smoking

Squamous carcinoma of the larynx arises from pre-existing lesions, the so-called "preneoplastic lesions". Hyperplastic lesions represent a part of their spectrum, from both clinical and biological points of view. On morphologic grounds, the most characteristic feature with prognostic value in the evaluation of preneoplastic lesions is dysplasia. It is not only nuclear alterations that are seen in the process of malignant transformation, the cytoplasmic pattern of cytokeratins changes through neoplastic progression, with a progressive reduction of the molecular weight of the produced species. Dysplasia also associates with gross alterations of the DNA content. This is in agreement with our finding of alterations of genes participating in the control of the cell cycle, p53 and p21(WAF1/cip1). p53 overexpression is detected in non-invasive squamous lesions (even in the absence of obvious dysplasia) and p21(WAF1/cip1) shows a dramatic change in the pattern of expression in dysplastic epithelium compared with the normal. However, not all genes participating in the control of the cell cycle are altered in early lesions. Overexpression of cyclin D1, a common phenomenon in advanced carcinomas, is not likely to participate in the early phases of neoplastic development.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cyclin D1; Cyclin-Dependent Kinases; Cyclins; DNA, Neoplasm; Epithelium; Genes, p53; Humans; Hyperplasia; Keratins; Laryngeal Diseases; Laryngeal Mucosa; Laryngeal Neoplasms; Oncogene Proteins; Precancerous Conditions

Leukoplakia is only a descriptive clinical term designating a white patch or plaque of the mucosa and must be complemented by histology. On the other hand, keratosis is an exclusively histological term denoting pathological production and accumulation of keratin on the surface of the laryngeal epithelium. Leukoplakia is usually keratosis, but not always. Keratosis can mask various epithelial changes, from simple hyperplasia to invasive squamous carcinoma and is only the superficially visible manifestation of an underlying pathological process. Keratosis means total replacement of superficial epithelial cells by keratin filaments, and dissolution of the nuclei. When nuclei are retained in keratinized cells, the process is termed parakeratosis. Therefore, keratosis can be classified as a separate entity only when histopathological examination reveals superficial keratotic changes accompanying a normal squamous epithelium. To identify the presence of keratosis in various benign laryngeal entities divided according to severity of epithelial abnormalities, and to determine whether keratosis has any prognostic value, we performed a retrospective analysis on bioptic material on 4,291 tissue specimens over a period of 15 years. Our results suggest that keratosis must be considered as only one sign of the disorder within the complex of other pathological changes and not as a distinct pathological entity. For this very reason, keratinization of the epithelial surface was not included among significant parameters used for the grading of epithelial changes into the particular group according to Kambic-Lenart classification.

Topics: Epithelium; Humans; Hyperplasia; Keratins; Laryngeal Diseases; Laryngeal Mucosa; Laryngeal Neoplasms; Leukoplakia; Prognosis; Retrospective Studies

An organotypic, tridimensional cell culture, also called a raft system, was used to study the influence of fibroblasts on epithelial carcinogenesis in a cell line derived from laryngeal squamous cell carcinoma and harboring a mutated p53. Differences between the effects of normal fibroblasts and those of tumor-derived fibroblasts were compared by means of fibroblasts taken from the normal skin and from the tumor of a cancer patient and cultivated with epithelial carcinoma cells in an organotypic culture. To study cell contact-mediated changes, the fibroblasts were either simply embedded in collagen matrix or additionally brought into direct contact with epithelial cells. Control epithelial cells were cultivated without any fibroblasts in an organotypic model. A protein panel [p53, p21, PCNA, bcl-2, Ki67, total cytokeratin (CK), CK 8, CK 10, CK 17, CK 18, CK 19, vimentin] involved in cell cycling and epithelial differentiation was assessed immunocytochemically in all organotypic cultures with fibroblasts, in tumor cells cultivated as a monolayer, and in the original tumor sample. The most dysplastic phenotype was obtained when tumor-derived fibroblasts were used in direct contact with epithelial cells, whereas the most benign phenotype was seen when skin fibroblasts had no contact with them. The intensive staining seen for p53 can be explained by p53 mutations also reflecting the weak expression of p21 and abundant expression of PCNA. The intensive Ki67 staining seen in all sections paralleled that of PCNA and marked active cellular proliferation. The CK staining pattern seen in cultured epithelia toward embryonic CKs, CK 8 and CK 18, suggested a simple epithelial phenotype. CK 19 was found only in the epithelium where no direct contacts had occurred. Vimentin expression increased when the raft epithelium was shifting toward a more benign phenotype. The results stress the importance of the origin of fibroblasts as well as the role of direct cellular contacts in modifying the epithelial phenotype even when the epithelial cells are malignant.

Topics: Adult; Biomarkers; Carcinoma, Squamous Cell; Cell Culture Techniques; Cell Cycle; Cell Differentiation; Cells, Cultured; Coculture Techniques; Epithelial Cells; Epithelium; Fibroblasts; Humans; Keratins; Ki-67 Antigen; Laryngeal Neoplasms; Male; Proliferating Cell Nuclear Antigen; Skin; Tumor Cells, Cultured; Vimentin; Vocal Cords

The immunohistochemical expression patterns of cytokeratin polypeptides and vimentin were investigated in normal epithelia and squamous cell carcinomas of the larynx with special emphasis on tumor grading. During malignant transformation of epithelial cells, the cytokeratin expression patterns changed, depending on the differentiation grade of the carcinomas. In low-grade carcinomas, the expression patterns were close to those of the normal epithelium. With increasing tumor grade, there was decreased expression of stratification cytokeratins and increased expression of basal cell, simple cell and hyperproliferation-related cytokeratins. Increasing tumor grade was also associated with the expression of vimentin, a cytoskeletal protein of mesenchymal cells. No relationship was found between vimentin expression and the presence of lymph-node metastases.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Epithelium; Humans; Keratins; Laryngeal Neoplasms; Larynx; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Reference Values; Vimentin

The expression of cytokeratins and vimentin was studied immunohistochemically in normal epithelium and 12 benign lesions of the vocal cord with the use of a broad panel of monoclonal antibodies against cytokeratins and vimentin. Histology showed that the various lesions contained hyperkeratotic, hyperplastic and atrophic epithelium, irrespective of their clinical appearance. Especially the Ck profile of the (hyper)keratotic lesions was changed in comparison with the native epithelium. Increased expression of the keratinization marker Ck 10 was associated with decreased expression of the stratification markers Cks 4 and 13. Expression of the basal cell marker Ck 14 and hyperproliferation-associated Cks 16 and 17 was increased in all the benign lesions, except in atrophic epithelium. These expression patterns differ from those observed in malignant epithelial lesions. The latter show a marked expression of simple cell Cks and vimentin and more pronounced expression of hyperproliferation-associated markers than the benign lesions.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epithelium; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Laryngeal Neoplasms; Vimentin; Vocal Cords

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

We investigated the incidence of micrometastases from squamous cell carcinomas of the head and neck in neck dissection specimens originally staged as pNO. A total of 76 dissection specimens from 60 patients were evaluated using serial microscopic sectioning in 10-microns intervals, H & E staining, and immunostaining with an antibody to pan-cytokeratin. Examination of 1,020 lymph nodes from 76 neck dissection specimens revealed 8 micrometastases (7.9%) in 6 specimens from 6 patients with oral and pharyngeal primaries, resulting in upstaging. Six micrometastases were located in lymph nodes 3 to 6 mm in diameter. The surgeon should be aware of the relatively high incidence of micrometastases from oral and pharyngeal carcinomas, which are undetectable preoperatively or by routine histopathologic examination. Primary tumor site (oral cavity and pharynx) and certain features of the primary can delineate a group of patients with a higher risk of harboring occult metastases who may benefit from elective treatment of the neck.

Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Histological Techniques; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Mouth Neoplasms; Neoplasm Staging; Pharyngeal Neoplasms; Prognosis; Retrospective Studies

The present study employed immunohistochemical methods to study the cytokeratin (ck) and vimentin expression in 40 cases of laryngeal squamous cell carcinoma. Specific monoclonal isoform antibodies and mixes of antibodies vs. a specific molecule were used in order to determine what cytokeratins were present as accurately as possible. In this sampling two ck patterns were identified based on whether the ck pair 8/18 was present or not. The ck 8/18 positive cases were further broken down into three sub-groups based on the expression of one of the following: the ck 4/13 pair, ck 1/10 pair or vimentin. A statistically significant relationship was found between these sub-groups, the site at which the neoplasm arose and the tendency toward regional metastases. Moreover, it was found that the presence of ck 13 in a squamous cell carcinoma is correlated with the less aggressive forms, as indicated in the literature.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Larynx; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Retrospective Studies; Vimentin

The characteristics of the deep invasive front area of squamous cell carcinomas may reflect tumour prognosis better than other parts of the tumour. Consequently, the authors have recently developed a simple malignancy grading system based solely on the characteristics of the deep invasive front area of oral squamous cell carcinomas, which has great prognostic value. Our previous materials were somewhat heterogeneous, and the prognostic value of our system needed to be confirmed in homogeneous patient material. In the present study of 95 T1-2/N0 glottic carcinomas all treated by radiation, the high prognostic value for invasive front grading of biopsy specimens is confirmed. The grading significantly predicted local recurrence, i.e. treatment failure (P = 0.001). Histological characteristics of the deep invasive front proved to be a better indicator of prognosis than the T-category (size of tumour), and our findings may be of value in the selection of treatment. Of the individual variables in the grading system (pattern of invasion, degree of keratinization, nuclear polymorphism and host response), pattern of invasion and degree of keratinization were the strongest prognosticators in the multivariate analyses. Invasive front characteristics may also prove to be of prognostic value in other cancers.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Glottis; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Prognosis; Survival Analysis

As part of a study on the relationship of tumour phenotype and behaviour, we have characterized two head and neck squamous cell carcinoma cell lines, derived from human laryngeal carcinomas and designated HLaC'79 and HLaC'82. Cytogenetic analysis revealed that HLaC'79 and HLaC'82 shared 10 major chromosome rearrangements indicating that the cell lines had a common origin. In the extremely complex chromosomal patterns, abnormalities were found in chromosomes 1, 3 (surplus 3q) and 5 (i(5p) x 2). Both cell lines displayed constitutive expression of vimentin and were capable of anchorage-independent growth in agarose gels. However, in spite of their common origin specific differences were found. Cells of HLaC'79 were spindle shaped and formed tumours in athymic mice. In contrast, cells of HLaC'82 had a compact morphology, contained less vimentin, were more contact inhibited and were not tumorigenic. These results indicate that malignant transformation in HLaC'82 was partially reversed.

Topics: Carcinoma, Squamous Cell; Cell Line; Cell Transformation, Neoplastic; Humans; Intermediate Filament Proteins; Intermediate Filaments; Karyotyping; Keratins; Laryngeal Neoplasms; Tumor Cells, Cultured; Vimentin

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

Human papillomaviruses (HPVs) are important human pathogens associated with a range of epithelial neoplasia. The rising incidence of HPV infection and association of HPV with malignancy has led to increased interest in appropriate management of these infections. Development of new therapies for viral warts has been frustrated by the lack of availability of models permissive for viral replication. Here we describe the development of HPV-severe combined immunodeficient mouse model which reproduces mature HPV-infected epithelia. Grafting of anogenital and laryngeal papillomas harbouring either HPV-6 or HPV-11 resulted in the formation of a differentiated neo-epithelium exhibiting the hallmark features of HPV infection including basal hyperplasia, acanthosis and koilocytosis. The reformed warty epithelium contained amplified HPV DNA and expressed capsid protein in the differentiated layers. A striking feature is the production of macroscopic papillomata in an anatomically relevant and accessible site, providing a system of particular relevance for the temporal evaluation of developing lesions and selection of antiviral agents.

Topics: Animals; Capsid; Condylomata Acuminata; Disease Models, Animal; DNA Replication; Epithelium; Gene Expression; Humans; Keratins; Laryngeal Neoplasms; Mice; Mice, SCID; Neoplasm Transplantation; Papilloma; Papillomaviridae; Papillomavirus Infections; Proliferating Cell Nuclear Antigen; Protein Precursors; Skin; Skin Transplantation; Transplantation, Heterologous; Tumor Virus Infections; Virus Replication

The expression of cytokeratin (CK) subclasses was immunohistologically investigated in normal laryngeal epithelia by the ABC technique using monospecific monoclonal antibodies. There are two types of epithelium in the larynx; squamous epithelium of the glottis and ciliated epithelium mainly of the supraglottis. A difference in expression pattern was observed between these two epithelia only in 3 CKs, specifically CK-8, CK-13 and CK-19. In the glottis, CK-8 was negative in all layers, CK-13 was positive in the suprabasal and superficial layers, and CK-19 was strongly positive in the basal layer, but apparently reduced in suprabasal layers and completely negative in the superficial layers. In the supraglottis, on the contrary, CK-8 was positive except in the basal layer, CK-13 was negative in all layers, and CK-19 was positive in all layers. When ciliated epithelia were reduced to squamous metaplasia, the epithelial cells were morphologically similar to the squamous cells, and the CK expression also showed the same pattern. In proximity to this squamous metaplasia, however, there were lesions whose cell type morphologically still resembled that of the ciliated epithelium, but whose pattern of CK expression had already been reduced to that of the squamous cell.

Topics: Carcinoma, Squamous Cell; Epithelium; Humans; Immunohistochemistry; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Larynx; Metaplasia

Laryngeal papillomas are benign epithelial tumors caused by human papillomaviruses. These tumors are characterized by hyperplasia of the spinous layer and abnormal differentiation. Many tumor cell lines over-express the epidermal growth factor (EGF) receptor on their surface, and EGF regulates normal cell growth. We have asked about the relationship of the EGF receptor and EGF response in laryngeal papilloma cells. Papilloma cells showed markedly greater immunohistochemical staining for the EGF receptor, compared to uninfected cells. Both cell types showed a 2-3-fold increase in nuclei incorporating bromodeoxyuridine when EGF was present. Removal of EGF from papilloma cells cultured on collagen rafts permitted normal stratification and differentiation, as determined by synthesis of keratin 13. Inclusion of EGF induced abnormal differentiation with minimal expression of keratin 13. Uninfected laryngeal cells cultured on rafts in the presence of EGF synthesize keratin 13 in all suprabasal cells. EGF reduced both human papillomavirus RNA levels in the papilloma cells and expression of a reporter gene linked to the human papillomavirus 11 enhancers and E6 promoter in uninfected cells. These results suggest that the phenotype of papillomas is induced, in part, by EGF binding to the abundant EGF receptors.

Topics: Cell Differentiation; Cell Division; Epidermal Growth Factor; ErbB Receptors; Humans; Keratins; Laryngeal Neoplasms; Papilloma; RNA, Viral; Tumor Cells, Cultured

The expression of distinct cytokeratin subtypes in squamous cell carcinomas (SQCC) of the larynx was examined by immunohistochemistry with a panel of monoclonal antibodies (MABs) and different immunophenotypes were correlated with known prognostic factors, such as tumor site, local extension, degree of morphologic differentiation and lymph node metastasis. Among 50 cases of laryngeal SQCC tested, all 22 low grade tumors (Broders I and II) reacted strongly with MABs AE1, AE3 and KB.12, which corresponds to the phenotype of non-neoplastic squamous epithelium of the larynx. MABs K8.13 and K8.60 were negative only in 1 and 4 cases respectively. In these tumors CAM5.2 was either negative (18 cases) or weakly positive (4 cases). In contrast, we found that of 28 high grade SQCC (Broders III and IV) tested, strong reactivity with MABs AE1, AE3, K8.12 and K8.13 was restricted to smaller subsets, whereas CAM5.2 immunoreactivity was seen in 16 cases (57%). By morphological criteria 31 out of 50 cases in our series of SQCC showed keratinization and 30 of these 31 showed coexpression of cytokeratins identified by MABs AE3, K8.12, K8.13 and K8.60 and 29 cases by MAB AE1. The remaining non-keratinizing SQCC showed heterogeneous immunoreactivity for AE1, AE3 and K8.12 in 13 cases, for K8.13 in 12 cases and for K8.60 in 5 cases. Thirty of the 50 SQCC tested had no known lymph node metastasis and of these, 29 reacted with MABs AE1, AE3, K8.12 and K8.13 respectively, the remaining cases being either unreactive or only weakly reactive. Statistical analysis showed no significant differences between cytokeratins expression in SQCC and either anatomical location or local extension (pT).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Prognosis; Reference Values; Staining and Labeling

Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF receptors) which were confined predominantly to the undifferentiated cells. The expression of this growth factor system in malignant cells may play a role in carcinogenesis and/or tumour growth. All carcinomas were positive for TGF-alpha and 12 were positive for EGF. In moderately-to-well differentiated carcinomas, the immunoreactivity was mainly detected in the cytologically more differentiated cells. Nine sections included both laryngeal stratified squamous epithelium of normal appearance and carcinoma. The immunoreactivity was here again localized in the cytologically more differentiated cells above the basal cell layer. The present investigation and our previous results confirm the existence of EGF receptors, TGF-alpha and EGF in laryngeal carcinomas. In addition, we conclude that the conditions do exist for growth factors to act through an autocrine system in poorly differentiated tumours and through a paracrine system in the moderately-to-well differentiated tumours.

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cytoplasm; Endothelium; Epidermal Growth Factor; Epithelium; Exocrine Glands; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Muscles; Laryngeal Neoplasms; Macrophages; Male; Mucins; Neoplasm Staging; Transforming Growth Factor alpha

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

We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas.

Topics: Cell Division; Cell Transformation, Neoplastic; Filaggrin Proteins; Humans; Immunoblotting; Intermediate Filament Proteins; Keratins; Laryngeal Neoplasms; Neoplasm Proteins; Papilloma; Papillomaviridae; Protein Precursors; Staining and Labeling; Thymidine; Tumor Virus Infections; Uridine

Expression of cytokeratins (CKs) was investigated immunohistochemically by use of monospecific monoclonal anti-CK antibodies in normal epithelia of pyriform sinus and epithelial lesions such as simple hyperplasia, different degrees of dysplasia, in situ carcinoma, and invasive carcinoma. In normal epithelium, strong expression of CK-19 was consistently observed only in the basal layer as basic CK, while expression of CK-13 showed a completely reverse pattern, being expressed only in suprabasal layers as stratification-related CK. Characteristic changes in expression pattern of these two CKs were observed in accordance with the degree of epithelial disorders and differentiation of carcinoma. Cytokeratin 1, as keratinization-associated CK, was observed only in keratinized cells of hyperplastic epithelia and well-differentiated carcinomas. These findings may be useful in evaluating epithelial disorders and classifying carcinomas more objectively, and may assist earlier detection of carcinoma when used with standard histologic techniques.

Topics: Antibodies, Monoclonal; Biopsy; Epithelium; Humans; Hyperplasia; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Larynx; Molecular Weight

Formalin- or alcohol-fixed, paraffin-embedded laryngeal specimens were stained immunohistochemically with several kinds of monoclonal anti-Keratin antibody (KL-1, PKK-1, PKK-2, PKK-3), polyclonal anti-Keratin antibody, and epithelial membrane antigen. Immunohistochemical technique was used by Avidin-Biotin Complex method with the following subjects; normal epithelium 6 cases, dysplasia 15 cases, inflammation and polyp 12 cases, squamous cell carcinoma 47 cases. 6 specimens of squamous cell carcinoma were totally resected and alcohol-fixed, and other specimens were all biopsied and formalin-fixed. Comparing these two methods, the alcohol-fixed specimen gave superior result to those obtained with formalin-fixed in its staining. Non-staining area was recognized around basal layer by KL-1 stain in the normal epithelium. Enlargement of non-staining area was recognized in the dysplasia. Also, KL-1 staining showed positive staining with the keratinizing squamous cell carcinoma, and weak staining with the non-keratinizing squamous cell carcinoma. And, PKK-3 showed weak staining in the keratinizing squamous cell carcinoma. The results indicate that high molecular weight keratin (56 kilodalton) hardly localize around the basal layer in the squamous epithelium, and also in the non-keratinizing squamous cell carcinoma. The other way, this also suggests that low molecular weight keratin (45 kilodalton) hardly localize in the keratinizing squamous cell carcinoma. It is supposed that intracellular localization of keratin of dysplastic epithelium and squamous cell carcinoma varies from that in the normal squamous epithelium. Accordingly, monoclonal keratin stain is thought to be an useful method for the diagnosis of dysplasia and squamous cell carcinoma.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Larynx; Membrane Glycoproteins; Molecular Weight; Mucin-1

Five cases of monophasic and 7 cases of biphasic spindle-cell carcinomas were analyzed immunohistochemically for the presence of vimentin and keratin type intermediate filaments in the pleomorphic spindle cells. Vimentin reactivity proved to be a consistent feature but keratin reactivity was more variable, this latter filament being lost in two cases initially presenting as pure squamous cell carcinomas showing dedifferentiation towards a pure monophasic spindle-cell tumour when recurring. The converse was also noted: acquisition of keratin in a monophasic spindle-cell tumour that recurred as squamous cell carcinoma. These results were considered to support the concept that spindle-cell tumours of the upper aerodigestive tract are a peculiar type of carcinoma and not a product of a pluripotent stem cell exhibiting bidirectional differentiation. Diagnostic implications are as follows: keratin positivity in a spindle-cell tumour substantiates its carcinomatous nature but its absence does not rule out a diagnosis of spindle-cell carcinoma.

Topics: Aged; Aged, 80 and over; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Neoplasm Recurrence, Local; Vimentin

Expression of immunocytochemically detectable markers in 100 cases of laryngeal carcinomas, homogeneous for staging and treatment, was correlated with clinical evolution of the disease. Follow-up for a minimum of 5 years was obtained in all cases. Paraffin sections were re-cut and stained in immunoperoxidase with monoclonal KL1, detecting medium-to-low molecular weight keratins, and with monoclonal HMFG2, revealing a surface glycoprotein. Expression of KL1-related antigen did not correlate with prognosis, whereas cases extensively positive for monoclonal HMFG2 (more than 50% cells stained) had a significantly better recurrence-free rate. In a group of tumors classified as Grade 3 (histologically poorly differentiated) and expressing a low degree of HMFG2-detectable surface glycoprotein (less than 50% cells stained), a high rate of recurrences (93%) was observed. This study indicates that the combined use of morphologic and biologic (immunohistochemical) criteria may constitute an independent parameter of primary importance in predicting the evolution of laryngeal carcinomas.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Laryngectomy; Membrane Glycoproteins; Neoplasm Recurrence, Local; Prognosis

The clinicopathological features of 14 laryngeal neoplasms consisting of spindle-shaped cells are presented. Light microscopy showed a variety of morphological patterns from that of pleomorphic sarcoma and fibrosarcoma to more loose vascular patterns. Immunohistochemistry revealed that the spindle-shaped cells had a positive keratin immunoreactivity in 8 of 14 cases, and also that some cases had a dual expression of keratin and vimentin filaments. Electron microscopy showed that spindle-shaped cells had epithelial ultrastructures. The results support the hypothesis that the spindle cell carcinomas are true carcinomas with mesenchymal metaplasia and that the spindle-shaped cells are part of the neoplasm and not benign, reactive fibroblasts. These lesions occurred mainly on the true vocal cords in elderly patients. The neoplasms were nearly all polypoid, and many also ulcerated. There is no significant difference in clinical behaviour between laryngeal spindle cell carcinomas and ordinary squamous cell carcinomas of the larynx, and the same treatment policy is therefore advocated. Being polypoid and therefore able to be surgically removed with relative ease, they may even present a more favourable clinical course.

Topics: Adult; Aged; Carcinoma; Collagen; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Microscopy, Electron; Middle Aged; Vimentin

Polypoid squamous cell carcinoma of the larynx consists of two components, namely, squamous cell carcinoma and sarcomatoid spindle cells. To further investigate the histogenesis of the spindle cell component, we studied two cases of polypoid squamous cell carcinoma of the larynx by immunohistochemistry and ultrastructural analysis. Positive staining for ras oncogene p21 and cytokeratin was demonstrated in both squamous cell carcinoma and spindle cell component. Only the latter component was positive for vimentin. Electron microscopic examination showed well-developed desmosomes in spindle cells. These results suggest that the spindle cell component is epithelial in origin and malignantly neoplastic; it originates from mesenchymal metaplasia or squamous cell carcinoma.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Microscopy, Electron; Middle Aged; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Vimentin

Human epidermal keratinocytes obtained from normal skin attached and spread on thrombospondin (TSP)-coated plastic dishes but failed to attach and spread on untreated plastic culture dishes or dishes coated with fibronectin or laminin. These cells produced minimal amounts of immunoreactive TSP. Keratinocytes established in culture on MCDB 153 medium and maintained for one to three passages in an undifferentiated state by continued cultivation in this low Ca2+-containing medium attached and spread on plastic dishes as well as on TSP-coated dishes. These cells also secreted significant amounts of TSP into the culture medium. When the keratinocytes were incubated for one day in MCDB 153 medium supplemented with high Ca2+ or in MEM (which also contains high Ca2+), there was decreased secretion of TSP into the culture medium concomitant with a reduction in attachment and spreading on plastic culture dishes. Proteolytic fragments of TSP were examined for stimulation of keratinocyte attachment and spreading. A 140-kd fragment produced by removal of the 25-kd heparin-binding domain had similar activity to the intact molecule while the 25-kd fragment was without effect. Further proteolytic treatment of the 140-kd fragment gave rise to a fragment consisting of 120 kd and 18-D moieties held together in disulphide linkage. This fragment did not support attachment or spreading. This study reveals that normal epidermal keratinocytes grown under conditions that maintain the undifferentiated state are able to produce TSP and utilize it as an attachment factor. When keratinocytes are grown under conditions that promote differentiation, ability to produce and utilize TSP is diminished. Since TSP is present at the dermal-epidermal junction and because TSP promotes keratinocyte attachment and spreading, this molecule may play an important role in maintaining normal growth of the basal cell layer and may also participate in reepithelialization during wound repair.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Adhesion; Cell Differentiation; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Epidermal Cells; Epidermis; Glycoproteins; Heparin; Humans; Keratins; Laryngeal Neoplasms; Oligopeptides; Thrombospondins; Tumor Cells, Cultured

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

In twenty-three cases of laryngeal dysplasia frozen mucosal strips were examined with four monoclonal and one polyclonal keratin antibody. The expression of specific keratin polypeptides was studied in different degrees of dysplasia with regard to the subunits expressed in normal and carcinomatous laryngeal epithelium in the same patient. An alteration in the expression of the subunits of cytokeratin in favour of low molecular weight polypeptides takes place in the transformation of normal epithelium to squamous cell carcinoma. This alteration seems to occur at an early stage and is present already in mild dysplasia. The results suggest that with a suitable antibody dysplastic laryngeal epithelium can be distinguished from normal epithelium, and also on some cases, mild dysplasia from more severe degrees of dysplasia. CAM 5.2, which identifies lower molecular weight cytokeratin proteins (50, 43 and 38 kD), is such an antibody, and can be a valuable diagnostic aid in the histological interpretation of laryngeal dysplasia.

Topics: Antibodies, Monoclonal; Carcinoma in Situ; Epithelium; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Larynx

Topics: Cell Differentiation; Epithelial Cells; Humans; Keratins; Laryngeal Neoplasms; Larynx

A laryngeal squamous cell carcinoma in situ with an underlying spindle cell nodule (pseudosarcoma) was immunohistochemically labeled with antibodies to tissue-specific intermediate filament proteins, including desmin, vimentin, and cytokeratin. Two distinct populations of cells were found within the lesion: cytokeratin-positive cells, corresponding to the carcinomatous component of the tumor, and vimentin-positive spindle cells in the subepithelial nodule. In view of the strict specificity of antivimentin and anticytokeratin for cells of mesenchymal and epithelial origin, respectively, it is proposed that the two components of the pseudosarcoma in our case are not morphologic variants of the same tumor, and that the subepithelial nodule represents a mesenchymal lesion. These results can, however, not be extrapolated to other cases since in some the spindle cell component may represent metaplastic epithelial cells. In view of the difficulties encountered in reaching a correct diagnosis in these lesions, it is recommended to use intermediate filament typing to elucidate the nature of the spindle cells in this controversial tumor.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Epithelium; Fibroma; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Laryngeal Neoplasms; Male; Middle Aged

For six patients with partial or total laryngectomies with extensive mucosal hyperplasias, we generated DNA histograms from multiple mucosal sites using Feulgen-stained tissue sections and microspectrophotometric microscopy. Aneuploid DNA histograms were identified in the mucosa of all six specimens, indicating that neoplastic transformation had occurred. The histologic characteristics of neoplastic change included thickened or hyperplastic epithelium, surface maturation or keratinization, often a proliferation of small, immature basallike cells in the depths of the epithelium, and evidence of abnormal epithelial maturation as evidenced by focal areas of cytoplasmic keratinization in the lower portions of the mucosa. We think this histologic expression of intraepithelial neoplasia is more common than the "classic" form of carcinoma in situ with full mucosal replacement by proliferating immature basallike cells. Keratin is a common reaction in laryngeal mucosa, and its presence on the surface or in the depths of the epithelium does not militate against the diagnosis of severe intraepithelial neoplastic transformation.

Topics: Aged; Carcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA, Neoplasm; Epithelium; Humans; Hyperplasia; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Male; Middle Aged

Poorly differentiated laryngeal carcinomas, which light microscopically are made up of anisomorphic nuclei, undifferentiated cytoplasm and hardly visible cell membranes, show electronmicroscopically a remarquable polymorphism. The tumor cells, which form solid or trabecular groups of different sizes often with poorly defined borderlines to the stroma, are subdivided according to their ultrastructural features in spinosa, secretory and stemcell types. Lymphocytes, plasmacells and reticular cells may show distinct focal proliferation or may be completely absent. In some cases, there was a transition between tumour tissue and metaplastic ciliated and glandular epithelium with concomitant reduction of normal glands. By comparison, besides hyperplastic and metaplastic squamous and ciliated epithelium, normal mucosal biopsies reveal invaginations of pseudostratified ciliated epithelium.

Topics: Actin Cytoskeleton; Carcinoma, Squamous Cell; Cell Nucleus; Cytoplasmic Granules; Desmosomes; Epithelium; Humans; Keratins; Laryngeal Neoplasms; Larynx; Microscopy, Electron

The effects of human papillomavirus infection, which can cause laryngeal papillomas, were studied in vitro in laryngeal stratified squamous epithelial cells. Interferon exposure had only minor effects on the outgrowth of primary cells from tissue fragments and the incorporation of tritiated amino acids by first-passage cells. There was a marked decrease in tritiated thymidine incorporation by papilloma cells when cultured in the presence of interferon, but no effect on thymidine incorporation by normal cells. Differentiation of laryngeal papillomas appears to be abnormal. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of keratins showed that the keratins of high relative molecular mass (Mr 51,000 and 59,000) associated with normal laryngeal differentiation were absent from papilloma tissue. Rather, both papilloma tissue and cultured papilloma cells contained a keratin of Mr 53,000 not normally present. Binding of the fluoresceinated lectin peanut agglutinin to cell surfaces suggested that there were alterations in the normal distribution of glycoproteins or glycolipids on papilloma tissues. Filaggrin, a protein synthesized by differentiating cells, was not detectable in most superficial papilloma cells after immunohistochemical staining. These studies strongly suggest that papilloma cells do not differentiate normally. We propose that this defect may be responsible for the hypertrophy of the tissue.

Topics: Adolescent; Adult; Autoradiography; Cell Differentiation; Cells, Cultured; Child; Child, Preschool; DNA, Viral; Electrophoresis, Polyacrylamide Gel; Female; Filaggrin Proteins; Humans; Infant; Infant, Newborn; Interferons; Intermediate Filament Proteins; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Nucleic Acid Hybridization; Papilloma; Papillomaviridae; Tumor Virus Infections

Various parameters of the local cellular response have been studied in 16 laryngeal papillomas from ten patients with recurrent papillomas as well as normal control laryngeal and tracheal tissue by indirect immunofluorescence on frozen sections using monoclonal antibodies specific for T-cell subsets, Langerhans cells (LC) and HLA-DR antigens. Keratinization was investigated with a monoclonal antibody KL1 recognizing an acidic 56.5 Kd keratin, which is a marker of suprabasal cells in stratified squamous epithelium and is absent from the basal layer. The presence of viral antigen was detected with a rabbit antiserum raised against SDS-dissociated purified virus. A mild inflammatory response was observed in most biopsies. Cytotoxic/suppressor T-cells were the predominant cells found in the lesions. Compared with normal epithelium, the number of LC was dramatically reduced in the papillomatous epithelium. High densities of HLA-DR-positive cells were found mainly in the corium. The keratinization process was disturbed in most specimens in that both basal and suprabasal compartments reacted positively with the KL1 monoclonal antibody. Viral antigen was present in the nucleus of very occasional epithelial cells in some samples.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Viral; Child; Child, Preschool; Fluorescent Antibody Technique; Humans; Immunity, Cellular; Keratins; Laryngeal Neoplasms; Papilloma; T-Lymphocytes

The histogenetic origin of the spindle-cell component of spindle-cell carcinoma of the head and neck mucosa remains controversial. The spindle cells have been considered a variant growth pattern of squamous-cell carcinoma, a non-neoplastic mesenchymal reaction, and a malignant admixture of epithelial and mesenchymal neoplasm. To evaluate the spindle-cell component, we studied 25 tumors (18 biphasic and seven monophasic) by utilizing the following: an avidin-biotin complex immunoperoxidase technique with a variety of antikeratin antibodies (AE1, AE3, CAM 5.2, 35BH11, and polyclonal Dako) and a monoclonal antivimentin antibody, and an avidin-biotin alkaline phosphatase double-labeling technique to detect coexpression of keratin and vimentin. The immunohistologic staining pattern was compared with electron-microscopic studies. Eight of 18 biphasic neoplasms contained immunoreactive keratin in the spindle-cell component that was distributed focally in a minority of cells in 3 tumors and diffusely throughout five of the neoplasms. Four of seven ulcerated monophasic spindle-cell tumors devoid of histologic squamous-cell carcinoma also were keratin positive, confirming epithelial differentiation. The majority of the spindle cells in all the tumors contained vimentin intermediate filaments. In three immunoperoxidase keratin positive biphasic tumors examined with alkaline phosphatase double labeling, occasional spindle cells were found that coexpressed keratin and vimentin and were interspersed with cells expressing either intermediate filament. Electron microscopy was performed on the spindle-cell component of 13 tumors, nine biphasic and four monophasic. Of the biphasic tumors, four were immunoperoxidase keratin positive; three of these showed epithelial differentiation by electron microscopy. Five biphasic tumors were keratin negative, and three tumors had epithelial differentiation by electron microscopy. Four monophasic spindle-cell tumors were immunoperoxidase keratin positive, and one of these had epithelial features by electron microscopy. Two monophasic tumors were keratin negative and without ultrastructural evidence of epithelial features. By using a combination of immunohistochemical and electron-microscopic observations, we identified evidence for epithelial differentiation in the spindled cells in 11 of 18 biphasic tumors and four of seven monophasic spindle-cell tumors.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Male; Microscopy, Electron; Middle Aged; Mucous Membrane; Vimentin

Topics: Epithelium; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Molecular Weight; Vocal Cords

The stratified squamous epithelium covering vocal cord polyps can vary from normal to hyperplastic and keratinized. We have analyzed the histology and cytokeratins of 11 of these polyps. Cytokeratins were separated on one-dimensional SDS-acrylamide gels to determine molecular weights. There was significant heterogeneity in the cytokeratins present in the different polyps. Comparison of histologic findings and cytokeratin content showed a correlation between extent of keratinization and presence of high molecular weight cytokeratins. We conclude that the epithelium of vocal cord polyps exhibit patterns of cytokeratins characteristic of both hyperproliferation and abnormal states of differentiation, which are mirrored by histologic variations, and that vocal cord polyps are a heterogeneous group of benign lesions.

Topics: Adult; Aged; Electrophoresis, Polyacrylamide Gel; Female; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Polyps; Vocal Cords

A 60-year-old white woman with laryngeal oat cell carcinoma is described. She was a heavy smoker who had been treated seven years earlier with 5,000 rads for a well differentiated squamous cell carcinoma metastatic to a left submandibular lymph node. She presented this time with a two month history of hoarseness and tumor of the supraglottic larynx was found. There was clinical and chemical evidence of an ectopic ACTH syndrome. The histology and fine structure of the tumor were typical of oat cell carcinoma. Immunoreactive ACTH, GRP, NSE, Beta-endorphin, calcitonin, and keratin were found in the cytoplasm of the tumor cells by indirect immunoperoxidase techniques. We could find no previously reported case of laryngeal oat cell carcinoma with ectopic ACTH syndrome or cytoplasmic localization of polypeptides.

Topics: Adrenocorticotropic Hormone; Autopsy; Carcinoma, Small Cell; Female; Gastrin-Releasing Peptide; Gastrins; Hormones; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Middle Aged; Peptides; Phosphopyruvate Hydratase

In the case of viral acanthomas, the stratum spinosum and granulosum presents ballooned cells which contain all transitional stages from multivesicular bodies (MVB) to keratinosomes. A particularity in condylomata acuminata are the "wagon-wheel" bodies. These structures are typical for the non keratinazed squamous epithelium. The participation of intercellular extruded "wagon-wheel" bodies, MVB and atypical keratinosomes on an irregular baso-apical diffusion-barrier in the epidermis of cases with viral acanthomas has been discussed. On the basis of the relation seen between MVB and the Golgi-apparatus, their transition to partially atypical keratinosomes in cases of viral acanthomas and their "expulsion" into the intercellular space could indicate that in keratinozytes the enzymatically regulated feed-back between the cellular surface and the capability to synthesize is changed by viral agents. The interference appears to manifest itself in the Golgi-apparatus and also appears to be "specified" by the terrain present.

Topics: Animals; Condylomata Acuminata; Cytoplasmic Granules; Epithelium; Humans; Keratins; Laryngeal Neoplasms; Microscopy, Electron; Papilloma; Skin Diseases; Skin Neoplasms; Tumor Virus Infections; Warts

Bleomycin has been shown to have a significant effect on squamous cell carcinomas, particularly on highly differentiated types. Applying combined bleomycin and x-rays simultaneously in an intermittent schedule, a synergistic effect was obtained. It was possible to lower the dosage of each and still achieve remarkable therapeutic responses. At the same time the side effects were reduced. The total dosages have been bleomycin 180 mg and x-rays 4.200 r skin dose, tumor dose approximately 2.500 r. Eighty-two laryngeal cases received such treatment. Altogether a complete regression was achieved in 62 per cent. Glottic tumors showed complete regression in 85 per cent. In six out of 10 inoperable cases, the tumor became surgically accessible by laryngectomy. In successfully treated patients characteristic histological changes were found, consisting in unusually large amounts of fully keratinized cells.

Topics: Aged; Animals; Biopsy; Bleomycin; Carcinoma, Squamous Cell; Drug Administration Schedule; Female; Humans; Keratins; Laryngeal Neoplasms; Larynx; Male; Mice; Middle Aged; Norway

The report deals with a case of epidermoid carcinoma of the vallecula with widespread sebaceous differentiaton. The sebaceous areas were first observed in a cervical lymph-node metastasis, which preceded the discovery of the primary lesion. No similar lesion has been described. Recent literature dealing with extracutaneous sebaceous lesions is cited.

Topics: Aged; Carcinoma, Squamous Cell; Epidermal Cyst; Epiglottis; Humans; Keratins; Laryngeal Neoplasms; Laryngectomy; Male; Neck Dissection; Neoplasm Metastasis

The patients with cancer of the larynx at the Ear, Nose and Throat Department in Zagreb during the period from 1945 to 1972, and the cases of laryngeal cancer at the Institute of Public Health of Croatia, were examined epidemiologically. The patients were from all parts of Croatia (West and south part of Yugoslavia) with the characteristics of Mediterranean and Continental climate. The following factors were discussed: age and sex distribution, localization of the tumor in three compartments of larynx, relationship between the villages and cities, occupation (peasants, workers and intellectual people), histologic types and the etiological factors (smoking and alcohol.

Topics: Adult; Age Factors; Aged; Albumins; Alcohol Drinking; Carcinoma, Squamous Cell; Female; Globulins; Glottis; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Occupations; Residence Characteristics; Sex Factors; Smoking; Yugoslavia

Topics: Animals; Antibiotics, Antineoplastic; Biopsy; Bleomycin; Carcinoma, Squamous Cell; Culture Techniques; Desmosomes; Ear Neoplasms; Epiglottis; Glycogen; Humans; Keratins; Laryngeal Neoplasms; Maxillary Neoplasms; Mice; Microscopy, Electron; Mouth Neoplasms; Neoplasms, Experimental; Palatal Neoplasms; Tongue Neoplasms; Tonsillar Neoplasms

Topics: Adult; Age Factors; Aged; Autopsy; Cell Nucleus; Epithelium; Humans; Keratins; Laryngeal Neoplasms; Larynx; Male; Middle Aged; Smoking; Vocal Cords

Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Granuloma; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Radium; Skin Diseases; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms