| Objective: The carcinoma of larynx is one of the malignant neoplasms inotolaryngology and head and neck surgery. Its incidence increasedsignificantly in recent years.The occurrence,development and metastasis oflaryngeal cancer is a process by multi-factor, multi-stage and multi-gene isinvolved, meanwhile by the activation of oncogenes, deactivation of tumorsuppressor genes and apoptogenes uncontrolled interactions. HMGA1proteinbelongs to the high mobility group (HMG) protein family members.HMGA1in the regulation of gene transcription, DNA replication, chromatin changes inthe cell cycle, chromatin remodeling plays an important role. HMGA1isclosely related to the occurrence and development of tumor. Hand1(alsonamed eHand/Hxt/Thing1) belongs to the Twist subfamily of Class BbHLH(basic helix-loop-helix) transcription factors. Hand1has essentialroles in both trophoblast giant cell differentiation and cardiac morphogenesis.A role of HAND1in cell proliferation and neoplastic transforma-tion alsohave important implications. Our aim is to investigate the expression ofHMGA1and HAND1gene in laryngeal carcinoma, to analyze their role in thetumorigenesis, progression, invasion and metastasis as well as theircorrelation.Methods：1Immunohistochemistry(Envision two-step methods) was employed tomeasure the expression of HMGA1and HAND1in42specimens oflaryngeal squamous cell carcinoma tissue and25specimens of adjacent tissue.2RT-PCR was employed to measure the expression of HMGA1andHAND1mRNA in42specimens of laryngeal squamous cell carcinoma tissueand25specimens of adjacent tissue.3Statistics analysis: SPSS13.0was applied to analyze the results of experiment.P<0.05indicating significant difference. P<0.01indicating verysignificant difference.Results：1Expression of HMGA1and relation with clinical parameter1.1Immunohistochemistry was employed to measure the expression ofHMGA1in42specimens of laryngeal squamous cell carcinoma tissue and25specimens of adjacent tissue. The positive expression rate of HMGA1proteinwere71.43%(30/42) and20.00%(5/25), the former was significantly higherthan the latter，There was very significant difference in the positive rates ofHMGA1protein between laryngeal squamous cell carcinoma tissues andspecimens of adjacent tissue.(P<0.01). The expression of HMGA1geneprotein in laryngeal squamous cell carcinoma tissues was significantly higherthan that in the specimens of adjacent tissue. Expression of HMGA1wascorrelated with lymph node metastasis,clinical stage(P<0.05)，but that wasn’tcorrelated with pathological grading of tumor,patients’ clinical classificationand age (P>0.05).1.2RT-PCR was employed to measure the expression of HMGA1mRNA in42specimens of laryngeal squamous cell carcinoma tissue and25specimensof adjacent tissue. In laryngeal squamous cell carcinoma tissues and thespecimens of adjacent tissue, the expression of HMGA1mRNA were1.25±0.21and0.96±0.33,the former was significantly higher than the latter,there was significant difference in the expression of HMGA1mRNA betweenthe two groups（P<0.01）. Expression of HMGA1mRNA was correlated withlymph node metastasis (P<0.05),clinical stage (P<0.01),but that wasn’tcorrelated with pathological grading of tumor, patients’ clinical classificationand age (P>0.05).2Expression of HAND1and relation with clinical parameter2.1Immunohistochemistry was employed to measure the expression ofHAND1in42specimens of laryngeal squamous cell carcinoma tissue and25specimens of adjacent tissue. The positive expression rate of HAND1proteinwere35.71%(15/42) and76.00%(19/25),the former was significantly lower than the latter.There was significant difference in the positive rates of HAND1protein between laryngeal squamous cell carcinoma tissues and specimens ofadjacent tissue (P<0.01). The expression of HAND1gene protein in laryngealsquamous cell carcinoma tissues was significantly lower than that in thespecimens of adjacent tissue.Expression of HAND1was correlated withlymph node metastasis,clinical stage and pathological grading of tumor(P<0.05),but that wasn’t correlated with patients’ clinical classification andage (P>0.05).2.2RT-PCR was employed to measure the expression of HAND1mRNA in42specimens of laryngeal squamous cell carcinoma tissue and25specimensof adjacent tissue. In laryngeal squamous cell carcinoma tissues and thenormal laryngeal mucosa specimens, the expression of HAND1mRNA were1.16±0.37and0.82±0.16, the former was significantly lower than the latter,there was significant difference in the expression of HAND1mRNA betweenthe two groups（P<0.01）. Expression of HAND1was correlated with lymphnode metastasis,clinical stage and pathological grading of tumor (P<0.05),butthat wasn’t correlated with patients’ clinical classification and age (P>0.05).3Correlations: mRNA level,There were negative correlations betweenHMGA1and HAND1expression (r=-0.998，P<0.01).Conclusions：1HMGA1and HAND1are expressed in all laryngeal squamous cellcarcinoma and specimens of adjacent tissue.2The higher expression of HMGA1and the lower expression of HAND1in laryneal squamous cell carcinoma may be contributed to the carcinogenesisand development of laryngeal carcinoma.3In laryngeal squamous cell carcinoma tissues, the higher expression ofHMGA1was correlated with lymph node metastasis,clinical stage，but thatwasn’t correlated with pathological grading of tumor,patients’ clinicalclassification and age;the weaker expression of HAND1was correlated withlymph node metastasis,clinical stage and pathological grading of tumor,butthat wasn’t correlated with patients’ clinical classification and age.It may contribute to the carcinogenesis and lymphatic metastasis of laryngealcarcinoma.4There were negative correlations between HMGA1and HAND1expression in laryngeal carcinoma tissue,It may be that HMGA1proteins binddirectly to Hand1promoter inhibit Hand1promoter activity. |
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