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- 伊海金副主任医师 博士后
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医院:
北京天坛医院
科室:
耳鼻喉科
- The role of molecular margins as prognostic factor in laryngeal carcinoma of Chinese
- 作者:伊海金|发布时间:2013-06-20|浏览量:481次
conclusion:
molecular margins were [cu1] more important prognostic factor in laryngeal carcinoma of chinese than histopathological margins. eif4e was t[cu2] sensitive molecular index [cu3] .北京天坛医院耳鼻喉科伊海金
objective: the safe surgical margins related closely with prognosis. aim of the present study is to investigate the role of molecular margins, not traditional histopathological margins, as prognostic factors in laryngeal carcinoma of chinese. [cu4] additional aim of the study was to investigate the prognostic significance of tumor markers in primary site of laryngeal carcinoma.
methods:
from january 1992 to january 2000, the data of 321 chinese patients [cu5] laryngeal carcinoma who were divided into recurrent laryngeal carcinoma group and non-recurrent group were analyzed .tumor markers in surgical margins and primary site, such as cyclind1、p53 and eif4e ,were detected in the two groups with immunohistochemical staining.
result:
there was significant difference about the expression of cyclind1、p53 and eif4e in[cu6] margins between recurrent laryngeal carcinoma group and non-recurrent group. eif4e positive rate in [cu7] margins is higher than the other two. there was significant difference about cyclind1 and p53 in primary site of laryngeal carcinoma and no significant difference about eif4e in the two groups.
key words:
immunohistochemical staining, cyclind1, p53, eif4e
introduction
laryngeal carcinoma is one of the common malignant tumors [cu8] department of otolaryngology-head and neck surgery .the effective treatment includes surgery, radiotherapy and chemotherapy. local recurrence after treatment is not uncommon, [cu9] from 10 to 50%. the prognostic about laryngeal carcinoma were complicated .the safe surgical margins related closely with prognosis. at present, the approach of judging the negative or positive surgical margins was based on routine pathological examination. the finding of histopathologically negative margins meant a good prognosis.[cu10] studies have shown molecular and biochemical abnormalities to occur prior to morphological changes in tumor cells; these changes at [cu11] molecular level often took precedence over pathological changes of tumor tissue. the concepts of molecular margins then were proposed and [cu12] such [cu13] few in laryngeal carcinoma of chinese. [cu14] aim of the present study is to investigate the role of molecular margins, not traditional histopathological margins, as prognostic factors in laryngeal carcinoma of chinese. [cu15] additional aim of the study was to investigate the prognostic significance of tumor markers in primary site of laryngeal carcinoma of chinese.
materials and methods
1. patient characteristics
from january 1992 to january 2003, 343 patients [cu16] laryngeal carcinoma were treated in the department of otolaryngology of peiking union medical college hospital, [cu17] were divided into recurrent laryngeal carcinoma group and non-recurrent group. the clinical staging of these carcinomas was performed according to their location and extension, based on tnm system, using the classification of american joint cancer committee (ajcc) and the international unit against cancer (uicc).
inclusion criteria included: ①accepted surgical treatment. ②had not received other treatment. ③had negative cell surgical margins and the pathology specimen were well preserved. ④had complete clinical data and follow-up of 5 years. ⑤all were squamous cell cancer. on this basis 115 patients were included in this study .there were 33 cases of laryngeal carcinoma in recurrent laryngeal carcinoma group, including 31 males and 2 females, aged from 44 to 80 years, average 62 years of age. and 82 cases of laryngeal carcinoma in non-recurrent group, including 75 male cases, 7 females, aged from 37 to 78 years, mean 58 years.
laryngeal tissue was [cu18] from paraffin pathological specimens. we detected the expression of cyclind1, p53, and e if4e in the primary tumors and surgical margins of the above two groups.
2. main material and sources
main material included cyclind1 (rabbit anti-human polyclonal antibody, za-0101), p53 (rabbit anti-human monoclonal antibody, za-0408), e if4e (mouse anti-human polyclonal antibody, sc-9976). these were purchased from beijing zhongshan golden bridge biotechnology co., ltd.
3. methods:
the expression of cyclind1, p53 and e if4e of all the surgical margins and primary site were detected by immunohistochemical method in laryngeal carcinoma recurrence and non-recurrent [cu19] . [cu20] cyclind1 and p53 [cu21] , e if4e were diluted to 1:50. the pbs buffer were used as negative control; known positive breast biopsy as a positive control.
1. resultsevaluation [cu23]
[cu24] of immunohistochemical staining: on immunohistochemical staining cyclind1 protein was predominantly located in the nucleus (also please reference this), thus brown staining of the nucleus was judged to be positive ? (where in the nucleus?). the judgment criteria of other factor were: brown and granular staining in nuclei with p53; red-brown staining in cytoplasm with e if4e. quantitative criteria: strongly positive(+++) :cell shading> 50%;positive (++):cell shading > 30% to 50%; weakly positive (+):cell shading 5% to 30% ; negative (-):<5% or without staining.
strongly positive, positive and weakly positive staining of cyclind1, p53 and e if4e were judged as positive result. all the margins of one specimen were detected, if one margin was positive in a specimen, then the specimen was judged as positive molecular margin.
2. statistical analysis
spss11.5 statistical package were used to analyze the results of the corresponding statistical data: count data by χ2 test with p <0.05 as statistically significant.
the expression of cyclind1, p53, e if4e was statistically significant difference in surgical margins of recurrent laryngeal carcinoma group and non-recurrent group (p <0.05), and the expression rate was: 52%, 64%, 85%, the positive rate of eif4e was the highest (p <0.05). the expression of cyclind1, p53 was statistically significant difference in primary site of recurrent laryngeal carcinoma group and non-recurrent group (p <0.05), the expression of e if4e was [cu25] statistically significant difference (p> 0.05) in the above two groups. the expression rate of cyclind1and p53 was 82%, 78%, and no significant difference (p> 0.05).
immunohistochemical figures.(?, ?, ?, positive expression of cyclind1, p53 and e if4e in primary tumo.???, in surgical margins.)
discussion
1. tumor markers of laryngeal carcinoma
cyclind1, p53 and e if4e [cu26] common tumor markers associated with the prognosis of tumor. the genes encoding cyclind1 protein are a proto-oncogene.under normal circumstances , the half-life of cyclind1 protein is shorter and rapidly degraded in the s phase when entering the cytoplasm .so cyclind1 can be detected only when cyclind1 protein are overexpressed [1] . recent studies showed that, overexpression of cyclind1 allowed cells [cu27] lose the dependence to growth factor ,cells constantly entered the cell cycle, resulting in the occurrence of malignant cancer. the over-expression of cyclind1 may play a significant role in the incidence and development of lscc (laryngeal squamous cell carcinoma) [2]. types of cyclin d are involved in the genesis of laryngeal squamous cell carcinomas, and the evaluations of biopsy samples may provide useful additional markers capable of identifying subgroups of patients with a poor prognosis[3 ]. p53 gene is divided into two types ,including wild and mutant type. mutant p53 gene allows the wild-type p53 gene inactivates and cause malignant cells to multiply. in head and neck tumors, alterations of the p53 proteins occur during the development of recurrent lscc. p53 and ki67 expression in tumoral tissue may be a prognostic marker in patients with laryngeal scc [4].eif4e (eukaryotic initiation factor 4e) is a eukaryotic translation initiation factor. the eukaryotic translation initiation factor 4e regulates the translation of cap-dependent mrnas. an aberrant increase in eif4e shifts the balance in favor of translation of transcripts that promote cell proliferation and malignancy. eif4e protein is commonly elevated in head and neck squamous cell carcinomas (hnscc), and its overexpression is associated with increased recurrence [5].eukaryotic initiation factor 4e can be considered as a tumor molecular marker and an independent prognostic molecular marker of laryngeal squamous cell carcinoma[6].
this paper detected the expression of cyclind1, p53 and e if4e in some of the recurrent laryngeal carcinoma group and non-recurrent group .the results indicated that: laryngeal carcinoma with positive result of cyclind1and p53 in primary tumor likely relapsed after operation, the positive expression rate of cyclind1and p53 showed no significant difference. (results shown in table 1-3 and color figures)
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2. molecular margin of laryngeal carcinoma
operation was one of the important methods in treatment of laryngeal carcinoma .the safe surgical margins related closely with prognosis, though there existed controversy[7-8].the margin study is an effective modality for ensuring the operative [cu28] of lscc and is recommended for all lscc procedures including intraoperative frozen section and postoperative specimens , [cu29] traditional laryngectomy or laser operation[9-10].
the relatively modest survival of patients surgically treated for advanced hnscc can partly be explained by the development of local relapse. it is important that surgeons are able to predict which patients are at high risk to develop local relapse. despite careful histopathological examination of the surgical margins of the primary carcinoma, it is at present not reliably possible to predict which patient will develop local relapse. herein we focus on new developments regarding the analysis of margins, causes of local relapse, and how novel molecular techniques can be of help in a more accurate risk assessment [11].
at present ,the approach of judging the negative or positive surgical margin was based on traditional pathological examination. the histopathologically negative surgical margins, that is to say, carcinoma cell were not found in the margins, meant a good prognosis. brandewein thought[12]that in the tumors, the change of molecular level often took precedence over pathological changes of tumor tissue. brandwein m and sidransky d [13] then proposed the concept of molecular margin and thought that the molecular margins based on the histopathological margins evaluated more accurately the prognosis of tumor. studies had shown that before the morphology of tumor cells changed significantly, the molecular level and the biochemical metabolic abnormalities have occurred [14].
the result of this study showed that the positive molecular margins [cu30] tumor relapse after surgery. eif4e positive rate was higher than the other two (p <0.05) showed e if4e was more sensitive molecular margin index. (results shown in table 1-3 and color figures).
the study on the recurrence of laryngeal carcinoma is a popular field .it is very important that [cu31] should be focused on validation and assessment of the clinical utility of these markers.
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