Carcinoma, Squamous Cell ; genetics ; pathology ; Esophageal Neoplasms ; genetics ; pathology ; Humans

OBJECTIVEIt is currently considered that the defect of mitotic spindle caused by centrosome abnormalities may be one of the reasons for the development of aneuploidy in tumors. This study attempted to elucidate the possible role of centrosome defects in the development and progression of OSCC by investigating the frequency of centrosome amplification in oral precancerous lesions and OSCC.

METHODSFormalin-fixed, paraffin-embedded tissues of 12 cases of normal oral epithelium, 22 case of dysplasia with different degree epithelium dysplasia and 32 cases of OSCC with different differentiation were investigated for centrosome status by using indirect immunofluorescence double staining with antibodies to centrosome protein gamma-tubulin and cytokeratin. The differences and the change trend of centrosome status in these groups were statistically analyzed by SPSS10.0.

RESULTSNormal oral epithelium showed normal centrosomes in epithelium cells, while 16 of 22 cases (72.73%) of dysplasia (DYS) and 27 of 32 cases (84.38%) of OSCC showed the evidence of centrosome amplification and morphological abnormalities characterized by huge size, clump or supernumerary centrosomes in a fraction of epithelium or tumor cells. The percentage of cells with abnormal centrosomes increased gradually from mild-dysplasia epithelium to poorly differentiated OSCC, which positively correlated with the histologicalcytologic grade of oral precancerous lesions and OSCC (P < 0.01).

CONCLUSIONCentrosome amplification was an early event and that might play a role in the establishment and perhaps the progression of OSCC. There might be some direct relationship between centrosome defects and the cellular morphological phenotype characteristics of dysplasia and OSCC. Centrosome amplification could be served as an alternative diagnostic indicator of dysplasia and the intervention of centrosome cycle might serve as a particular way for the prevention and treatment of OSCC in the future.

Carcinoma, Squamous Cell ; genetics ; pathology ; Centrosome ; pathology ; Humans ; Mouth Mucosa ; pathology ; Mouth Neoplasms ; genetics ; pathology ; Precancerous Conditions ; pathology

In order to elucidate the dynamic changes of oncogene expression in the sequential cascade of squamous metaplasia, dysplasia, and squamous cell carcinoma of the bronchial epithelium, hybridization in situ was employed with a biotinylated oncogene probe. The expression of c-myc was localized exclusively in nuclei. While normal bronchial epithelium revealed no discernible clumps of c-myc grains, except occasional grains less than 3 per cell, squamous metaplasia showed increased number of grains and a few clusters of c-myc grains. In dysplasia, c-myc expression was more intensive than in squamous metaplasia. Approximately, 1/3 to 2/3 of tumor cell populations of squamous cell carcinomas of the lung revealed tremendously increased c-myc expression. In addition clumpy grains of c-myc in squamous cell carcinoma appeared more frequently than in squamous metaplasia or dysplasia. The c-myc expression was found to vary between different samples and within each cancer, and not all cancer cells expressed c-myc. These data indicate that c-myc oncogene plays it's role on reprogramming for growth control of cell populations particularly in multistage carcinogenesis and progression of lung cancer. These dynamic alterations of c-myc expression suggest that neoplastic transformation may occur conceivably at the dysplastic phase eventually resulting in carcinoma in situ. This means, in turn, squamous dysplasia is a putative precancerous lesion of the human lung.
Bronchial Neoplasms/*genetics/pathology ; Carcinoma, Squamous Cell/*genetics/pathology ; Cell Transformation, Neoplastic/*genetics ; DNA ; Humans ; Metaplasia ; Nucleic Acid Hybridization ; *Oncogenes

OBJECTIVETo investigate the relationship between centrosome abnormalities and aneuploidy in oral squamous cell carcinoma (OSCC) and elucidate the possible underlying mechanisms of chromosome instability (CIN) in OSCC.

METHODSFormalin-fixed, paraffin-embedded tissues of 8 cases of normal oral epithelium and 32 cases of OSCC were examined for centrosome status by using indirect immunofluorescence staining, and chromosome instability (aneuploidy) in some tissues were detected by flow cytometry. The correlation between centrosome abnormalities and aneuploidy in OSCC was statistically analyzed by SPSS12.0.

RESULTSNormal oral epithelium showed normal size and number of centrosomes in epithelium cells, while 25 out of 32 cases of OSCC showed the evident centrosome amplification characterized by huge size and/or supernumerary centrosomes in a fraction of tumor cells, and 21 out of 32 cases were aneuploidy. The percentage of cases with abnormal centrosomes in aneuploid OSCC (19/21) was significantly higher than that in diploid OSCC(6/11) (P =0.032). Centrosome abnormality was significantly correlated with aneuploidy (Spearman r = 0.413, P = 0.047), and a positive correlation was found between the degree of centrosome amplification and the degree of DNA ploidy abnormality (Pearson r = 0.364, P = 0.041).

CONCLUSIONSCentrosome abnormality may be a contributing factor for chromosome instability in OSCC.

Aneuploidy ; Carcinoma, Squamous Cell ; genetics ; pathology ; Centrosome ; pathology ; Chromosomal Instability ; Humans ; Mouth Mucosa ; pathology ; Mouth Neoplasms ; genetics ; pathology

OBJECTIVE: To observe expression of stathmin gene in laryngeal squamous cell carcinoma (LSCC) and relation between expression of stathmin gene and occurrence and development of LSCC. METHOD: The expression of the stathmin gene was determined in 35 LSCC of specimens and 18 normal laryngeal tissues (NLT) of specimens by in situ hybridization with Digoxigenin labeled probe of stathmin mRNA. RESULT: Expression of stathmin gene was observed in 35 cases of laryngeal squamous cell carcinoma tissue (positive rate, 69%) and positive signal was observed in both cytoplasm and nuclear. Among 18 cases of normal tissue, only 6 showed weak positive signal. There was significant difference in expression of stathmin gene between laryngeal squamous cell carcinoma tissue and normal tissue. CONCLUSION Expression of stathmin gene may play a key role in the pathogenesis and development of laryngeal squamous cell carcinoma. It may be a very important biotherapy target in the treatment of laryngeal squamous cell carcinoma.
Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Gene Expression ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; pathology ; RNA, Messenger ; genetics ; Stathmin ; genetics ; metabolism

OBJECTIVETo investigate the amplification of EMS1 gene in the carcinogenesis of oral mucosa.

METHODSA total of 78 subjects, including 30 patients with oral leukoplakia (OLK), 33 with oral squamous cell carcinoma (OSCC), and 15 healthy controls, were studied. By using microdissection method, we obtained normal mucosa, hyperplastic epithelia, mild-dysplastic epithelia, moderate-dysplastic epithelia, severe-dysplastic epithelia and primary OSCC tissue. Then we analyzed EMS1 amplification by using differential PCR.

RESULTSEMS1 amplification began from moderate-dysplastic epithelia and occurred in 20.0% OLK cases and 57.6% OSCC cases. In the progress of OSCC, no gene amplification was observed in normal tissues, non-dysplastic OLK and mild-dysplastic OLK, while in the cases with metastasis, amplification frequency increased significantly (P = 0.015).

CONCLUSIONSEMS1 amplification parallels with the progress of oral carcinogenesis, indicating their potential roles in oral carcinogenesis.

Carcinoma, Squamous Cell ; genetics ; pathology ; Case-Control Studies ; Cortactin ; genetics ; Gene Amplification ; Humans ; Leukoplakia, Oral ; genetics ; pathology

OBJECTIVETo investigate the effects of microRNA-519b-3p (miR-519b-3p) on laryngeal carcinoma Hep-2 cell growth, and to analyze the underlying molecular mechanisms.

METHODSThe effects of miR-519b-3p on the growth and cell cycle of Hep-2 cells transfected with miR-519b-3p mimic were tested by MTT assay and flow cytometry, respectively. The mRNA and protein expressions of the related genes were tested by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. The expressions of miR-519b-3p were tested by real-time RT-PCR in 48 pairs of laryngeal carcinoma and adjacent tissue samples.

RESULTSThe expression of miR-519b-3p in laryngeal carcinoma tissues was significant lower than that in adjacent non-cancerous tissues (S(ΔCt) = 2.989, t = 2.693, P < 0.01) . Increasing the level of miR-519b-3p inhibited significantly Hep-2 cell proliferation, arrested the cell cycle in the G2/M phase (10.29% ± 4.63%, t = 4.395, P < 0.05) , and decreased significantly the percentage of cells in the S phase (7.56% ± 2.05%, t = 3.555, P < 0.05) , with the increase in the expression of cyclin dependent kinase (CDK) 1 and the decrease in the expressions of CDK 2 and Cyclin A. RT-PCR and Western blot showed that miR-519b-3p down-regulated the protein but not mRNA expressions of HuR and cyclooxygenase-2(COX-2) genes.

CONCLUSIONSThe expression of MiR-519b-3p as carcinoma suppressor gene is low in laryngeal carcinoma. The cell cycle of Hep-2 cells was arrested in the G2/M phase by MiR-519b-3p.

Carcinoma, Squamous Cell ; genetics ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Laryngeal Neoplasms ; genetics ; pathology ; MicroRNAs ; genetics ; RNA, Messenger ; genetics ; Transfection

OBJECTIVE: To examine the microsatellite instability and loss of heterozygosity in the pathogenic mechanism of laryngeal squamous cell carcinomas. METHOD: Forty cases squamous cell carcinomas of larynx were analyzed by comparing tumorous tissues and normal tissues around with 3 microsatellite markers from chromosome 3, 5 and 11, using PCR and PGE-AgNO3 staining. RESULT: Among the 40 cases of laryngeal squamous cell carcinomas, 87.5% (35/40) of samples showed microsatellite instability or loss of heterozygosity in one to three microsatellite markers. High frequent microsatellite abnormal occurred at D5S592, it was 70% (28/40). Then the mutation rate of D3s1228 was 52.5% (21/40). CONCLUSION Our study revealed that tumor suppressor genes nearby chromosome 3p14 and 5q23 regions related to the pathogenesis of squamous cell carcinomas of larynx. A correlation between microsatellite alternation and stage of the tumor were found in D3s1228 and D5s592 chromosome regions.
Carcinoma, Squamous Cell ; genetics ; pathology ; Genes, Tumor Suppressor ; Humans ; Laryngeal Neoplasms ; genetics ; pathology ; Loss of Heterozygosity ; Microsatellite Instability ; Neoplasm Staging

OBJECTIVETo identify the differentially expressed genes related to lymphatic metastasis of lung squamous cell carcinoma.

METHODSSpecimens of primary lung squamous cancer tissues and regional lymph nodes were obtained from 10 patients undergoing complete surgical resection of the tumor. The samples were classified into 3 groups, namely the primary tumor with lymphatic metastasis (TxN+, n=5), primary tumor without lymphatic metastasis (TxN-, n=5) and matched tumor cells from the metastatic lymph nodes (N+, n=5). The total RNA extracted from the laser microdissected primary tumor or metastatic nodes was labeled and hybridized with the microarray containing 6 000 known human genes or ESTs. Data analysis was performed using GeneSpring(TM) 6.2 software. Immunohistochemical staining was used to detect the expression of CCL20 in the specimens.

RESULTSA total of 37 genes showed differential expressions between TxN+ and TxN- tissues, among which 8 genes were upregulated and 29 were downregulated in TxN+ group. No genes, however, showed distinct differential expressions between N+ and TxN+ tissues. The expression of CCL20 was significantly higher in TxN- than in TxN+ tissues (P<0.05).

CONCLUSIONThe acquisition of the metastatic phenotype may occur early in the development of lung squamous cancer. The gene expression signature of lung squamous cell carcinoma is valuable to elucidate the molecular mechanisms regarding lymphatic metastasis of the malignancy, and may provide important clues for exploring novel therapeutic targets.

Carcinoma, Squamous Cell ; genetics ; pathology ; DNA Fingerprinting ; Gene Expression ; Gene Expression Profiling ; Humans ; Lung Neoplasms ; genetics ; pathology ; Lymphatic Metastasis

Adenocarcinoma ; pathology ; Carcinoma, Small Cell ; pathology ; Carcinoma, Squamous Cell ; pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms ; classification ; genetics ; pathology ; World Health Organization