Font Size: a A A

Eukaryotic Cell Translation Initiation Factor 4e And Cyclin D <sub> 1 </ Sub> Expression In Head And Neck Cancer And Its Clinical Significance

Posted on:2005-08-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:M HanFull Text:PDF
GTID:1114360152498223Subject:Otorhinolaryngology
Abstract/Summary:PDF Full Text Request
Background: Malignant transformation was thought to be a multistage and multi-step process. Canceration of cells included changes of genotype and phenotype. It was well knowen that not a single factor produced a marked effect in the process. Internal and external factors cooperated on the changes of cellular genes, including gene amplification, mutation and chromosome re-arrangement, to lead to activation of oncogene and inactivation of anti-oncogene. Sometimes these factors infected transcription and expression of genes which adjusted cell growth and differentiation to produce cell abnormal proliferation and differentiation, chromosome changes, protein or enzyme abnormal expression and changes of cell membrane's component. The resent discovery of genomic instability as another potential cause of tumourigenesis, as demonstrated by the dysfounction of DNA mismatch repair gene MSH2 in hereditary nonpolyposis colon cancer, has resulted in a revision in thinking of malignant transformation beyond dominant oncogene and tumor suppressor gene. Following more and more oncogene and anti-oncogene were detected, scholars gained enormous success in their correlation themry and clinical studies.Messenger RNA molecules are capped with a 7-methyl guanosine molecule ( m~7GpppN ) and recognized specifically by the cap-binding protein, eukaryotic initiation factor 4E (eIF4E). The cap structure is playing an important role in mRNA metablism, splicing, 3'distal end processing, traffic, stability and translation to adjust protein synthesis. In solid tumonrseIF4E overexpression is necessary to perform malignant proliferation. Since 1996, eIF4E has been regarded as a useful oncogene in head and neck to estimate prognosis and design treatment plan.Objective:To detect in situ expression of eIF4E in head and neck malignant and benign samples with qualitative and semiquantative evaluation, and to in-vestigate the mechanism of eIF4E in head and neck tumour development and clinical significance combined clinical data including age, sex, pathologic type and grade, TNM stage, site and recurrence.Material and Methods: Fifty paraffin sections of fifty patients were collected from those patients who troubled in head and neck malignant tumours or benign lesions. All the samples were provided by the department of otolaryngology of Qilu hospital of Shandong University from September 2002 to May 2003, and were diagnosed by two skilled pathologists.1 .Experimental group: there were 40 malignant tumour samples, among which were 31 men and 9 women whose age from 38 to 78, on an average of 62.1. According to origin site, these tumours included 20 larynx, 8 hypopharynx, 4 esophageal, 2 tonsil, 3 maxillary sinus, 2 base of skull and 1 cervical part. According to pathologic type, these tumours inclouded 37 squamous carcinomas (92.5%), among which were 13 well differentiation, 16 moderate differentiation and 8 poor differentiation, 1 malignant mixed tumour, 1 small cell sarcoma and 1 papillary squamous carcinoma. According to TNM, these tumours included 15 Ti, 2> 21 T3, 4, 17 No? 19 Nj. 3 , and all of these did not metastasize. There were 31 preliminary diagnosis cases and 9 recurrence cases.2.Control group: there were 10 benign specimens, among which were 7 men and 3 women whose age from 5 to 48 on an average of 32.8. All benign specimens were similar site biopsies from noncancer patients, and included 6 tonsil, 2 inferior turbinate, 1 soft palate. The specimens ' pathologic diagnosis were inflammation and hyperplasia of prostate.eIF4E in head and neck tissues were examined with SABC immunohistochemical method by antigen heat retrival. All positive cell of eIF4E were perinuclear and cytoplasm stained in buffy. According to Pavelic ' s histochemical semiquantative method in 1992, the strength of immunohistochemical staining was determined by cell intensity and percentage of positive cell. Cell intensity included: 0 was achromatic color, 100 was weak staining, 200 was moderate staining, 300 was strong staining. Chose 5 areas under low power lens and counted 100 cells in per area under high lens, and then calculated the positive percentage. eIF4E integra was product of multiplication of the intensity and percentage. Statistic analysis was carried between eIF4E integra malignant and benign samples. Compared the eIF4E integras according clinical data including age, sex, pathologic type and grade, TNM stage, site and recurrence. All measurement data(x + s) were analysed with one-way ANOVA.Results: The distribution of positive cells had some regularity. In head and neck cancer positive cells that were general 3~5 layers looked like a band in the basilar part and prickle cell layer. In squamous carcinomas, especially well differentiation, the positive cells mainly distributed around the cancerous nests and the basilar part. Horny pearls and parakeratosis cells in cancerous nests' centres were stained negative. The positive cells were distribution of mass, even diffusion, in moderate and poor differentiation. In head and neck cancer staining of positive cells was strong, whereas in benign samples was weak.eIF4E overexpressed in all 40 samples of head and neck cancer , whereas no or weak staining were detected in 10 benign lesions samples. eIF4E integra of head and neck cancer was 137.43+13.66. As the control, the integra was only 4.80+1.96. There were significance between malignant and benign samples (P<0.05) . eIF4E integra did not correlate with age , sex ,site of tumour and pathologic type (P>0.05) .eIF4E integra of Ti. 2 was 73.29± 13.41, T3, 4 was 182.33+14.38; No was 102.16±20.53, N1-3 was 168.79+15.17; There were significance between expression of eIF4E withTNM stage ( P < 0.05 ) , moreover eIF4E integra gradually increased following by raising of stage. The integra of well differentiated malignant tumours was 75.86 + 20.07, moderate differentiation was 168.99± 17.65, and poor differentiation was 175.37 + 21.92. The difference between poor differentiation and the other two groups was significant ( P < 0.05 ) , whereas there were no significance between well and moderate differentiation ( P > 0.05 ) . There were no correlation between eIF4E integra of preliminary cases(126.34 ± 14.65)and recurrence(180.20 + 31.75) (P=0.079), but eIF4E integra of recurrence had the tendency to heighten.Conclusion: l.The distribution of eIF4E in tissue and cell under light microscope matched its physiological function and physiological activity of tumour. It was a sensitive molecular marker to differ the nature of samples and malignant degree.2.eIF4E overexpressed in all samples of head and neck cancer, whereas no or weak staining were detected in benign samples. When eIF4E was overexpression, we should consider the opportunity of canceration connecting clinical situation, and adopt measures to treat. When the samples were too small to diagnose, eIF4E staining could be a useful reference.3.eIF4E integra did not correlate with site of tumour and pathologic type, whereas there were significance between expression of eIF4E of T stage and pathologic grade. eIF4E could reflect sensitively the malignant degree and help make diagnosis when it was difficult to diagnose only according clinic and microscopic examination. We should adopt amplified surgery or therapeutic alliance if eIF4E integra was high.4.There were significance between expression of eIF4E of No and N1.3. When eIF4E staining was positive in lymph nodes of No, we should consider the opportunity of recessive metastasis and adopt the most suitable surgical program to lengthen the living time without tumours.5.There were no correlation between eIF4E integra of preliminary cases and recurrence, but eIF4E integra of recurrence had the tendency to...
Keywords/Search Tags:Head and Neck Neoplasms, Eukaryotic Initiation Factor 4E, Immunohistochemistry
PDF Full Text Request
Related items