| Objective: Fanconi anemia (FA) is an autosomal recessivegentic disease, which molecular basis is inactivation of the FA/BRCA pathwaycause DNA repair dysfunction. As the key protein of FA/BRCA pathway, somescholars have found that the expression of FANCD2in ovarian cancer andcervical cancer were abnomal. However, there is a lack of agreement about thecorrelation between FANCD2expression and tumor occurrence and prognosisof patients. Head and neck squamous cell carcinoma (HNSCC) is one of the FApatients’ susceptible tumors. There are only few studies about FANCD2expression in HNSCC currently. This study aimed to investigate the expressionof FANCD2in nasopharyngeal carcinoma (NPC), nasoparyngeal mucosa, andrecurring NPC patients’ nasopharynx tumor and metastatic neck lymph nodetissues after routine radio-chemotherapy. Then the correlations of FANCD2expression and patients’ clinicopathological characteristics and outcome wereanalyzed. The values of FANCD2expression in diagnosis, cure and prognosiswere also evaluated. Methods: One hundred and twelve patients with NPC whowere diagnosed at the Affiliated Hospital of Luzhou Medical College from2003.01to2006.12were retrospectively included in this study. Eightyspecimens of nasopharyngitis mucosu were collected in the same period as thecontrol group. The state of survival and recurrence were obtained by telephone,letter and outpatient check. The expression of FNACD2in all specimens was detected by immunohistochemistry SP method. The Image-Pro Plus6.0imageanalysis system was utilized to evaluate the FANCD2expression level in meanoptical density (MOD=SumIOD/SumArea). Combined with patients’ clinicaldata, the correlation between FANCD2expression and clinicopathologicalparameteraracteristics was analyzed. The correlation between FANCD2expression and patients’ recurrence and prognosis was also analyzed, combinedwith patients’ follow-up date. Results:(1)Immunohistochemistry studydemonstrated that FANCD2expression was prevalent in NPC tissues and theMOD value was0.113±0.056, which was statistically significant lower thanthat in the control nasopharyngeal mucosa (0.068±0.036)(t=6.717，P=0.000).The positive localization of FANCD2was mostly cytoplasm, seldom nucleus;(2)The MOD value of FANCD2expression in different differentiated NPCtissues was respectively0.120±0.058in poorly differentiated NPC tissues,0.078±0.023in moderately-well differentiated NPC tissues, the difference wasstatistically significant(t=5.273，P=0.000).(3)The MOD value of FANCD2expression in twelve recurring NPC patients metastatic neck lymph node tissueswas0.119±0.061, the MOD value of the same patients in nasopharynx tumortissues before recurrence was0.136±0.050, there was no statistic significantbetween these two groups(t=0.760，P=0.455).(4)The MOD value of otherthirty-one patients in recurring nasopharynx tumor tissues was0.087±0.033, theMOD value of the same patients in nasopharynx tumor tissues at first diagnosiswas0.133±0.055, the phenomeno of FANCD2expression in recurring NPCnasopharynx tumor tissues lower than the control had statistic significant (t=3.972，P=0.000).(5)There was a negative correlation between FANCD2expression and T stage, N stage, clinical stage and course of disease (all P＜0.05), however the FANCD2expression was not correlated wite age, gender,the first symptom and the hobby of smoking and alcohol.(6)The dendline offollow-up was2013.1. The overall survival rate of all NPC patients was33.0%in all follow-up period. The1-year,3-year and5-year overall survival rate of allNPC patients was84.8%,61.6%and51.8%separately, and the median survivaltime was67months. The5-year disease-free survival rate of all NPC patientswas46.4%, and the median disease-free survival time was57months.Forty-seven patients suffered tumor recurrence, the recurrence rate was42%and seven patients suffered distant metastasis, the others were local recurrence.Among all local recurrence patients, there were28patients with purenasopharynx recurrence,9patients with pure neck recurrence, and3patientswith nasopharynx and neck recurrence.(7)Define the high and low FANCD2expression with the median of all specimens’MOD value(0.090149), there were25patients suffering from local reccurence in55cases FANCD2high epressiongroup(MOD＞0.091194) during follow-up period and the local reccurence ratewas45.5%. Similarly, there were15patients suffering from local reccurence in57cases FANCD2low epression group (MOD≤0.091194) during follow-upperiod and the local reccurence rate was26.3%. The local reccurence rate inFANCD2high expression group was higher than that in FANCD2lowexpression group (χ2=4.466, P=0.035).(8)The overall survival rate inFANCD2high expression group was38.2%, instead, it was33.3%in low expression group. There was no statistic significant between them (χ2=1.390，P=0.238).The disease-free survival rate in FANCD2high expression group was25.5%, and31.6%in low expression group. Log-rank test revealed that thedifference was statistic significant (χ2=4.289, P=0.038).(9)In terms ofprognostic values, Kaplan-Meier analysis indicated that T stage(χ2=25.493,P=0.000), clinical stage(χ2=37.373, P=0.000)and local recurrence(χ2=15.827,P=0.000)was correlated with overall survival separately, but the overallsurvival was not correlated with N stage, age, the hobby of smoking andalcohol and the first symptom (all P＞0.005).(10)Multivariate Cox regressionmodel analysis revealed that only clinical stage was correlated with NPCpatients prognosis(P=0.000， HR=4.884，95%CI:2.647~9.009)whereasFANCD2expression was not a valuable prognosis factor(P=0.604).Conclusions:(1) The expression of FANCD2mainly locates in cytoplasm. Itsexpression in NPC tissues is higher than that in nasopharyngitis mucosu tissues.It is suggested that FANCD2expression could be correlated with NPCcarcinogenesis.(2)With the differentiated degree decreasing, the expression ofFANCD2increase, there may be some correlation between FANCD2expression and NPC malignant degree, and this need further study.(3)Theexpression of FANCD2in pre-recurrence NPC nasopharynx tumor tissues ishigher than that in post-recurrence NPC nasopharynx tumor tissues. Wespeculate the down-regulation of FANCD2expression may be correlated withpatients’ recurrence.(4)There is a negative correlation between FANCD2expression and T stage, N stage, clinical stage and course of disease. With the development of NPC, the expression of FANCD2is down regulation.(5)Theexpression of FANCD2is correlated with local recurrence rate. Higherexpression patients are prone to recurrence.(6) FANCD2expression iscorrelated with disease free survival rate, it may be a prognosis factor, but ourresearch doesn’t demonstrate that it was an independent prognosis indicator forNPC patients’ survival. The prognosis predictive value of FANCD2needs to befurther study. |
PDF Full Text Request