Studies On Expression Of Apoptosis And Its Related Genes In Nasal And Paranasal Sinus Neoplasm And Their Relationship With Clinical Characteristics

It is has been estimated that the incidence of nasal and paranasal sinus carcinoma is 3% of the head and neck neoplasm which ranks the 3rd in neoplasm of Department of Otolaryngology. Currently the selection and execution of therapeutic methods have certain limitations. It, therefore, is necessary to search new markers to choose patients with high risk of poor prognosis and develop a new kind of therapy for effective treatment of nasal and paranasal sinus carcinoma. To provide bases for optimizing therapeutic methods, the treatment results in patients with nasal and paranasal sinus carcinoma from a large retrospective cohort were reviewed in the present study. And the relationship between spontaneous apoptosis and its relevant genes, survivin and fhit, the correlation between the clinicopathologic parameters and the above values in primary nasal and paranasal sinus carcinomas were investigated.Part One: Clinical Study122 patients who were treated between January of 1990 and March of 2001 with a minimum follow-up of 3 years were reviewed retrospectively. The 5-year overall survival rate, disease-free survival rate and local control rate were 53.78% > 40.29%and 45.93%, respectively. In multivariate analysis, age more than 50 years, extension to sphenoid sinus, dura, internal carotid artery and surgery alone remained significant. Most of the local recurrences of nasal and paranasal sinus carcinomas occurred within 2 years after the last therapies. The recurrences were closely related to patho logical types and differential degrees of the neoplasm. The results suggest that the combined therapy of operation and postoperative radiation is effective method for patients with nasal and pranasal sinus carcinomas.Combined with adjuvant methods, the indications for the preservation of eyes in patients with orbital invasions may be broadened. All the patients having the surgeries of nasal and paranasal sinus neoplasm should be closely followed up within the next 2 years after the operations.Part Two: Basic StudyTUNEL accompanied by HE and PI stain, immunohistochemistry using SP method, microdissection, PCR and the DHPLC were used to detect the spontaneous apoptosis, expressions of survivin and /hit, and the LOH at D3S1234 mirosatellite locus in fhit in archived paraffin-embedded formalin-fixed tissues of 48 primary nasal and paranasal sinus carcinomas for the first time. AI, expressions of survivin and fliit were evaluated according to the patients' prognoses. AI was strongly correlated to the early stage of tumor (P=0.048). SURVIVIN protein was expressed in 23 patients(47.92%) which was negatively correlated to the low AI (r= -0.393, P=0.006) . The AI in group of positive expression of gene survivin was statistically lower than that of negative expression (P=0.015). And tumors with late T stage had more positive expression of survivin than early ones did. All the normal tissues adjacent to tumors and all the nasal benign neoplasm showed high expression of fhit. The negative expression of FHIT protein was found in 5 patients (10.42%) and reduced expression compared to normal tissues in 16 patients (55.17%). The expression of FHIT protein was positively correlated to AI (r=0.379, P=0.008 ) and had no relation with the expression of survivin. The intensity and area of expression of FHIT protein in adenoid cystic carcinomas were significantly larger than squamous cell carcinomas (P =0.04) .The frequencies of MSI were 17.65% (3/17) at D3S1234. And the rates of LOH were 42.86% (3/7) . Among all the 3 patientswith LOH of D3S1234 locus , 2 (2/3, 66.67%) had lost or decreased expression of FHIT protein. The Kaplan-Merier analysis showed that low AI, positive expression of survivin and lost or reduced expression of fliit were significantly related to worse overall survival(P=0.04, 0.03 and 0.01 respectively).The above results imply that detection of apoptosis and expression of survivin may help to choose patients with high risk of poor prognosis. The inactivation of fliit gene may participate in the occ...