| Abstract: Objective: According to classical immunology theory,immunoglobulin (Ig) is the specific product of mature B lymphocytes. However,a plenty of studies have revealed Ig expression was found in various cancer celllines and carcinomas which suggested Ig expression might be involved intumorigenesis and progression. In vitro, some of the studies regarding thebiological function of Ig derived from tumor cells suggested that Ig is a growthpromoter of cancer cells and the cell growth can be suppressed throughblocking its expression. A number of studies have reported on the ectopicexpression of Ig, yet there has been a lack of understanding in its clinical andprognostic significance, as well as whether different isotypes of Ig maintaindifferent biological functions or not. This study aimed to investigate theexpression of IgM in resected specimens of human laryngeal squamous cellcarcinoma (LSCC) and the surgical marginal tissues, then the correlations ofIgM expression and patients’ clinicopathological characteristics and outcomewere analyzed. Besides, the diagnostic, therapeutic and prognostic value of IgMexpression was evaluated. Methods: Sixty five patients with LSCC whounderwent surgical resection at The Affiliated Hospital of Luzhou MedicalCollege from1998.02to2000.12were retrospectively included in this study.Their complete clinicopathological and follow-up data were preserved. Thirty four other specimens were collected in the same period from the mucosa ofLSCC patients, which were at least0.5cm far away from the tumor margin andused as the control group. Immunohistochemistry (SABC method) was utilizedto evaluate the expression and localization of IgM in LSCCs (n=65) andnegative laryngeal tissues (n=34). Analysis of the association between IgMexpression and its localization was then performed together withclinicopathological characteristics and patients’ prognosis. Results:(1)Immunohistochemistry study demonstrated that IgM expression was prevalentin LSCC tissues, positive staining was observed in63.1%(41/65) LSCCspecimens, which was statistically significant higher than in negative laryngealtissues (14.7%,5/34)(χ~2=20.977, P<0.001).(2) The localization of IgM wascell membrane and/or cytoplasm, and it had a tendency to shift from themembrane to the cytoplasm as the squamous cell became less differentiated.This tendency was statistically significant according to Chi-square trendanalysis (χ~2=8.453, P=0.003).(3) Chi-square analysis revealed IgM expressionwas correlated with lymph node metastasis (χ~2=6.442, P=0.011) and tumorstage (χ~2=4.996, P=0.025). Expression level of IgM in N0(no regional lymphnode metastasis) and stageⅠ+Ⅱ (early tumor stage) specimens wasstatistically significant higher than that in N1-3and stage Ⅲ+Ⅳ specimens,respectively. The IgM expression was not correlated with age, gender, course ofdisease, T stage, tumor anatomical site or cell differentiation.(4) The5-yearoverall survival rate of all LSCC patients was63%, and the median survival time was not reached. The5-year disease-free survival rate of all LSCC patientswas49%, and the median disease-free survival time was59.2months. Thirtysix patients suffered tumor recurrence, the recurrence rate was55.4%and all ofthem were local recurrence. Chi-square analysis revealed IgM expression wascorrelated with local recurrence (χ~2=5.925, P=0.015) which indicated that thelocal recurrence rate was statistically significant lower in IgM positive stainingspecimens than in the negative staining ones.(5) In terms of prognostic values,Kaplan-Meier analysis indicated that T stage (P=0.004), lymph node metastasis(P=0.006), tumor stage (P=0.01) and local recurrence (P<0.001) was correlatedwith overall survival. The overall survival rate of IgM positive and negativegroups were61.0%and41.7%, respectively. But there was no statisticaldifference between these two groups (P=0.055). The disease-free survival rateof IgM positive and negative groups were56.1%and25.0%, respectively.Log-rank test revealed that IgM expression was significantly correlated withenhanced disease-free survival (χ~2=8.343, P=0.004). In the subgroup containingthe41positive staining specimens, differences in subcellular localizations(membrane or cytoplasm) were not correlated with overall survival rate(χ~2=0.471, P=0.493) or disease-free survival rate (χ~2=1.873, P=0.171) of IgMpositive LSCC patients. And there were no correlation between expression levelof IgM and patients’ overall survival rate (χ~2=0.114, P=0.171) or disease-freesurvival rate (χ~2=0.132, P=0.716), as well. In multivariate Cox regressionmodel, only tumor stage was indicated as a poor prognostic factor (P=0.032, HR=8.236,95%CI:1.203~56.387) whereas IgM expression was not a valuablefactor (P=0.740). Conclusions:(1) IgM over-expression was prevalent inLSCC while there was no expression or low expression level in surgicalmarginal mucosa tissues of LSCC patients. It is suggested that IgM expressioncould be valuable in assistant diagnosis of LSCC.(2) The localization of IgMhad a tendency to shift from the membrane to the cytoplasm as the squamouscell became less differentiated, but the exact mechanism and function of thisdistribution diversity warrants further investigation.(3) The expression level ofIgM was inversely related to nodal status, tumor stage and local recurrencewhich indicated that the IgM expression is associated with early phases oflaryngeal tumorigenesis and as LSCC progressing, the expression level of IgMwas decreased.(4) IgM expression was correlated with enhanced disease-freesurvival and this might have implications in patients’ favorable outcome. But inthis study, IgM is not an independent predictive factor and its prognostic valuedeserves further study. |
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