Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC) worldwide. Protein phosphatase 2A (PP2A) dysfunction has been widely reported in a broad range of malignancies due to its distinctive role in miscellaneous cellular processes. However, it is poorly understood whether aberrant alterations of PP2A are involved in the network of oncogenic events in LSCC. Here, we detected a panel of PP2A-associated proteins using western blot in both laryngeal squamous cell carcinoma tissues and paired adjacent normal tissues from patients (Data S1). We found that phospho-PP2A/C (Y307), α4, cancerous inhibitor of protein phosphatase 2A (CIP2A), Akt, ezrin, phospho-ezrin (T567), 14-3-3, and focal adhesion kinase (FAK) showed increased expression levels in carcinoma tissues relative to normal tissues, while phospho-Akt (T308) showed decreased levels. Our study, thus, provides a rationale for targeting PP2A to develop novel therapies and proposes a combination of interrelated biomarkers for the diagnostic evaluation and prognosis prediction in LSCC.
Autoantigens/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Case-Control Studies ; Cytoskeletal Proteins/metabolism* ; Focal Adhesion Kinase 1/metabolism* ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Laryngeal Neoplasms/metabolism* ; Larynx/metabolism* ; Membrane Proteins/metabolism* ; Phosphorylation ; Protein Phosphatase 2/metabolism*

PURPOSE: We tried to evaluate the difference in the expression of carbonic anhydrase (CA) III and heat shock protein (Hsp) 70 between laryngopharyngeal reflux disease (LPRD) and non-LPRD patients. MATERIALS AND METHODS: The study involved 28 patients who underwent laryngeal microsurgery due to benign laryngeal disease from March to August 2008. Reflux symptom index (RSI) and reflux finding score (RFS) were measured for each person, and they were assigned either to the LPRD group (n=10) or non-LPRD group (n=18). Tissue samples were obtained from the mucosa of posterior commissure, and immunohistochemistry (IHC) staining of CAIII and Hsp70 was performed. The IHC scores were measured and compared with clinical features including RSI and RFS. RESULTS: Total 10 patients were assigned as LPRD group, and 18 patients were as control group. The mean IHC score of CAIII and Hsp70 was 1.70+/-1.06 and 1.90+/-0.88, respectively, in LPRD patients, whereas the mean IHC score of CAIII and Hsp70 was 0.78+/-0.73 and 0.94+/-0.87, respectively, in non-LPRD patients. The difference between two groups was statistically significant (p<0.05). CONCLUSION: CAIII and Hsp70 expressions were higher in LPRD patients that in non-LPRD patients, suggesting the possibility as one of biomomarker in LPRD diagnosis.
Adult ; Aged ; Biopsy ; Carbonic Anhydrase III/*metabolism ; Case-Control Studies ; Female ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; Immunohistochemistry ; Laryngopharyngeal Reflux/*diagnosis/surgery ; Laryngoscopes ; Laryngoscopy ; Larynx ; Male ; Middle Aged ; Mucous Membrane/*metabolism

OBJECTIVETo investigate the expression of microRNA-10a-5p (miR-10a) in laryngeal epithelial premalignant lesions (LEPL) and to analyze the correlations of its dysregulation with clinicopathologic parameters of LEPL.

METHODSAccording to the WHO classification (2005), 94 cases of LEPL were grouped into mild dysplasia (MID), moderate dysplasia (MOD), severe dysplasia (SD) and carcinoma in situ ( CIS). The expression of miR-10a in 94 cases of LEPL was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and correlated with the clinical and follow-up data of all LEPL patients.

RESULTSmiR-10a was down-regulated in LEPL with increasing grade of dysplasia. There was significantly statistical difference between low-risk ( MID + MOD) and high-risk ( SD + CIS) lesion groups (P = 0.03). The linear regression analysis showed that miR-10a was correlated with grade and gender of LEPL (P < 0.05).

CONCLUSIONSDown regulation of miR-10a may be a useful molecular marker for grading of LEPL and diagnosis of early laryngeal cancer.

Biomarkers ; Carcinoma in Situ ; metabolism ; pathology ; Down-Regulation ; Humans ; Hyperplasia ; pathology ; Laryngeal Neoplasms ; metabolism ; pathology ; Larynx ; pathology ; MicroRNAs ; metabolism ; Precancerous Conditions ; metabolism ; pathology ; RNA, Neoplasm ; metabolism ; Real-Time Polymerase Chain Reaction

OBJECTIVE: To investigate the expression of Survivin, p53 and Ki67 in laryngeal carcinoma and the relation with clinical data. METHOD: Immunohistochemical staining (SP) was used to detect expression of Survivin, p53 and Ki67 of 64 cases with laryngeal carcinoma, 26 cases with precancerosis, 34 cases with vocal polyps. RESULT: The positive expression rates of Survivin, p53 and Ki67 were 59.4%, 68.8%, 65.6% respectively in laryngeal carcinoma, which were significantly higher than those in precancerosis and vocal polyps (P < 0.01). The expression of Survivin, p53 and Ki67 in laryngeal carcinoma were significantly statistical different in TNM stage and lymph node metastasis (P < 0.05), but were not correlated with patients' ages, the pathological grades, 3 years and 5 years surviving rates (P > 0.05). The expression of Survivin, Ki-67 and p53 was positively correlated (r = 0.607, 0.541, 0.648, P < 0.01) in laryngeal carcinoma. CONCLUSION Survivin, p53 and Ki-67 may play an important role in the carcinogenesis and progress of laryngeal carcinoma. They may play synergetic roles in the process of carcinogenesis of laryngeal carcinoma.
Carcinoma, Squamous Cell ; metabolism ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; metabolism ; Ki-67 Antigen ; metabolism ; Laryngeal Neoplasms ; metabolism ; Larynx ; Lymphatic Metastasis ; Polyps ; metabolism ; Survivin ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVE: To investigate osteopontin (OPN) expression in plasma and tissue of patients with layngeal squamous cell carcinoma and analyze its role in invasion, metastasis, and clinical significance in laryngeal quamous cell carcinoma. METHOD: Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect expression of OPN in plasma and tissue of 60 cases of laryngeal squamous cell carcinoma, 20 cases of adjacent normal laryngeal tissue and 20 cases of plasma from healthy subjects. RESULT: The expression of plasma OPN was closely correlated with clinical stage and cervical lymphatic metastasis in laryngeal squamous cell carcinoma (P < 0.05), but no significant correlation with the tumor location, pathological grade, gender and age (P > 0.05). The expression of OPN increased in plasma during cancer development: laryngeal squamous cell carcinoma (38.089 ± 9.225) ng/ml, healthy subjects (18.563 ± 9.308) ng/ml. There was a significant difference between the groups (P < 0.05). The expression of OPN in tissue was closely correlated with clinical stage (P < 0.05), pathological grade (P < 0.05) and cervical lymphatic metastasis (P < 0.05) in laryngeal squamous cell carcinoma adjacent atypical hyperplastic epithelium and carcinoma. The expression of OPN increased in tissue during cancer development: laryngeal squamous cell carcinoma (56.67%), adjacent normal laryngeal tissue (15.00%). There was a significant difference between the groups (P < 0.05). Elevated expression of plasma OPN is positively correlated with the expression of OPN in tissue in laryngeal squamous cell carcinoma patients (r = 0. 871, P < 0.05). CONCLUSION OPN plays an important role in the infiltration, metastasis and carcinogenesis in laryngeal squamous cell carcinoma. Combination of serum OPN, tissue OPN detection can be used as diagnostic and surveillance indicators for laryngeal squamous cell carcinoma infiltration and metastasis.
Carcinoma, Squamous Cell ; metabolism ; pathology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Head and Neck Neoplasms ; metabolism ; pathology ; Humans ; Hyperplasia ; pathology ; Immunohistochemistry ; Laryngeal Neoplasms ; metabolism ; pathology ; Larynx ; pathology ; Lymphatic Metastasis ; Neck ; Osteopontin ; metabolism ; Squamous Cell Carcinoma of Head and Neck

OBJECTIVE: To study the expression of DNA-dependent protein kinase (DNA-PK) in human laryngeal squamous cell carcinoma (LSCC) and normal laryngeal mucosa (NLM), and to analysize the relationship between the expression and the clinicopathologic parameters of LSCC. METHOD: Immunohistochemical technique (Envision) was used to detect the expression of DNA-PK in 64 cases of LSCC and 15 cases of NLM. To investigate an investigation was conducted on the relationship between the expression and clinico-pathological features of LSCC. RESULT: DNA-PK was lowly expressed in NLM and highly expressed in LSCC,the positive rate of DNA-PK expression was 26.67% (4/15), 78.13% (50/64), respectively, and there was significant different difference between the two groups (P < 0.05). Its expression was correlated with the level of histodifferentiation (P < 0.05), but not with TNM stages and neck lymph node metastasis (P > 0.05). CONCLUSION DNA-PK may be involved in disease development of LSCC.
Aged ; Carcinoma, Squamous Cell ; enzymology ; pathology ; DNA-Activated Protein Kinase ; metabolism ; Female ; Head and Neck Neoplasms ; enzymology ; pathology ; Humans ; Laryngeal Mucosa ; enzymology ; Laryngeal Neoplasms ; enzymology ; pathology ; Larynx ; enzymology ; Lymph Nodes ; Lymphatic Metastasis ; Male ; Middle Aged ; Squamous Cell Carcinoma of Head and Neck

OBJECTIVE: The aim of this study is to investigate the expression of hypoxia inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) in laryngeal carcinoma and its relations to clinical and pathophysiological characteristics, and determine the effect of HIF-1alpha, VEGF in the processing of angiogenesis. To offer the theoretical basis for the pathogenesis of laryngeal carcinoma and the new ideas for early diagnosis of laryngeal carcinoma. METHOD: The major was divided into two groups:60 specimens of laryngeal carcinoma and 20 specimens of normal tissues beside the carcinoma. The expression of HIF-1alpha, VEGF was detected in 60 specimens of laryngeal carcinoma tissues and 20 specimens of normal tissues beside the carcinoma as controls by immunohistochemical staining technique. Microvessel was stained by antifactor CD105 antibody to analyse microvessel density. RESULT: Positive rate of HIF-1alpha and VEGF protein expression was 71.67% (43/60) and 65.00% (39/60) respectively in laryngeal carcinoma tissues, which was significantly higher than that in normal laryngeal tissues (10.00% and 20.00%, respectively). HIF-1alpha expression was closely related to P-TNM stage, the grade of cell differentiation and lymph node status; VEGF expression was closely related to P-TNM stage and lymph node status. The coincidence rate of the expression of HIF-1alpha and VEGF was 56.67% (34/60), showing a close relation between them. MVD was much higher in tumor with HIF-1alpha(+)/VEGF(+) than that in tumor with HIF-1alpha(--)/VEGF(--) (P < 0.01). CONCLUSION HIF-1alpha protein and VEGF was over-expressed in laryngeal carcinoma. The positive expression of HIF-1alpha, VEGF and MVD in laryngeal carcinoma have a synergistic effect on the neovascularization of the tumor.
Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Laryngeal Neoplasms ; blood supply ; metabolism ; Larynx ; metabolism ; Male ; Microvessels ; Neovascularization, Pathologic ; etiology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVE: To investigate the expression of MCM2, Ki-67 and Rb and its biological characteristic in human laryngeal squamous cell carcinomas(LSCC). METHOD: The expression of MCM2 protein and Rb protein were detected in 60 cases of LSCC, 10 cases of precarcinoma, 10 cases of vocal cord polyps and 10 cases of normal laryngeal tissues, and Ki-67 protein were detected in 60 cases of LSCC and 10 cases of normal laryngeal tissues by Elivision plus immunohistochemical staining, and analyze their relations with clinicopathological characteristics. RESULT: The positive expression rate of MCM2 in LSCC was significantly higher than that in precarcinoma and normal laryngeal tissues (P < 0.05), and was positively correlated with pathological grades, clinical stages and lymph node metastases (P < 0.05) of LSCC. The positive expression rate of Rb protein in LSCC was significantly lower than that in precarcinoma and normal laryngeal tissues (P < 0.05). The expression level of MCM2 in LSCC was negatively corelated with Rb (r = -0.542, P < 0.05), the expression level of Ki-67 in LSCC (76.67%) was significantly higher than that in normal laryngeal tissues (30.00%) (P < 0.01) and the expression level of MCM2 in LSCC was positively corelated with Ki-67(r = 0.596, P < 0.01). The LI of MCM2 in the 3-year survival rate of LSCC was significantly lower than that in Ki-67 (P < 0.05). CONCLUSION Over expression of MCM2 and loss of Rb protein were related to the carcinogenesis and development of LSCC. The determination of MCM2 can be an index for estimating the level of malignancy and prognosis of LSCC.
Carcinoma, Squamous Cell ; metabolism ; mortality ; pathology ; Cell Cycle Proteins ; Humans ; Ki-67 Antigen ; metabolism ; Laryngeal Neoplasms ; metabolism ; mortality ; pathology ; Larynx ; metabolism ; Lymphatic Metastasis ; Minichromosome Maintenance Complex Component 2 ; metabolism ; Neoplasm Proteins ; metabolism ; Polyps ; metabolism ; Precancerous Conditions ; metabolism ; mortality ; pathology ; Retinoblastoma Protein ; metabolism ; Survival Rate ; Vocal Cords ; metabolism

OBJECTIVE: To study the expression of PD4, CD44 and PCNA proteins in laryngeal carcinoma and their relationships with the pathogenesis, development and prognosis of laryngeal carcinoma. METHOD: Immunohistochemistry was used to study 140 cases of laryngeal carcinoma tissues, 25 cases of precarcinoma tissues, 36 cases of vocal cord polyps and 13 cases of normal tissues adjacent to laryngeal carcinoma. RESULT: 1. The positive rates of PD4, CD44 and PCNA were 45.71% (64/140), 64.29% (90/140) and 77.86% (109/140) in laryngeal carcinoma, which were much higher than in non-carcinoma tissues (P < 0.01). 2. The third and fourth stages laryngeal carcinoma express stronger PD4 and CD44 than those of the first and second stages. Laryngeal carcinoma with cervical metastasis had higher expression than those without cervical metastasis. To 3 and 5 years' survival, PD4, CD44 and PCNA positive cases had lower chance than those negative cases(P < 0.01 or 0.05). 3. The over all positive rate of PD4, CD44 and PCNA was 27.86% (39/140) in laryngeal carcinoma tissues and 5.41% (4/74) in non-carcinoma tissues. CONCLUSION The high expression of PD4, CD44 and PCNA proteins maybe closely related to the pathogenesis, development and prognosis of laryngeal carcinoma.
Adult ; Aged ; Aged, 80 and over ; Apoptosis Regulatory Proteins ; metabolism ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Laryngeal Neoplasms ; metabolism ; pathology ; Larynx ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proliferating Cell Nuclear Antigen ; metabolism ; RNA-Binding Proteins ; metabolism

OBJECTIVE: To investigate the expression of collagen type I (Col I), collagen type IV (Col IV) and fibronectin (Fn) in laryngeal squamous cell carcinomas (LSCC) and their pathobiological relationship with invasion and metastasis of tumor. METHOD: The expression of Col I, Col IV and Fn was detected by immunohistochemistry method in normal tissue of latero-carcinoma and tissue of carcinoma in 60 specimens of LSCC. Integral optical density (iOD) was detected by image analysis of computer and was analyzed by SPSS13.0. RESULT: The expression of Col I was obvious and integrity. The expression of Col IV and Fn of basal membrane was like intact line-shape appearance and Fn of interstitial substance appeared like a complete network in the normal tissue of latero-carcinoma. Their expression decreased gradually and their integrity was broken and disappeared gradually from well to poorly differentiated LSCC. Their expressions also fell off with the tumor size, clinical stage and cervical lymphatic metastasis gradually and consistently in LSCC. Their variances were statistical significance separately (P<0.05 or P<0.01). CONCLUSION The expression of Col I, Col IV and Fn was closely related to tumor invasion, the regional lymph node metastasis and other some pathobiological features in LSCC. A detection of Col I, Col IV and Fn was of definite significance on a better comprehension of the possibility of metastasis, choice of surgery and prognosis.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Collagen Type I ; metabolism ; Collagen Type IV ; metabolism ; Female ; Fibronectins ; metabolism ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Larynx ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis