| Objective(s):Lung cancer is the malignancy with the highest mortality rate.Invasive mucinous adenocarcinoma is a subtype of lung cancer,the incidence of which has been increasing year by year in recent years with poor prognosis.In this study,we analyzed the expression and distribution of different mucins and transcription factors in invasive mucinous adenocarcinoma and investigated their correlation with clinicopathological features and prognosis to identify immune markers to guide grading,and relevant predictive factors affecting the prognosis of patients with invasive mucinous adenocarcinoma.Methods:144 cases of invasive pulmonary mucinous adenocarcinoma diagnosed pathologically by postoperative resection specimens between January 2015 and June2022 at the First Affiliated Hospital of Kunming Medical University were collected for retrospective analysis and reclassified according to the latest criteria of the 5th edition of the WHO Lung Tumor Classification.Tumor tissues and paired normal tissues surrounding the tumor(control group)were selected separately from the case specimens and the expression of TTF-1,HNF4 a,TFF-1,MUC1,MUC4,MUC5 AC and MUC6 proteins was detected by using En Vision immunohistochemical staining to analyze the distribution,expression characteristics and interrelationship of different mucins and transcription factors in different tissue structures of mucinous adenocarcinoma.The prognostic differences in different tissue structures were compared by Kaplan-Meier survival curve analysis.Univariate and multivariate Cox regression analyses were applied to determine the independent predictors of poor prognosis in mucinous adenocarcinoma.Statistical analysis of the data was carried out using SPSS(20.0)statistical software.Results:1.Out of 144 patients diagnosed with mucinous adenocarcinoma of the lung,62 were males while 82 were females.Based on the latest lung tumor classification standards,mucinous adenocarcinoma was categorized as pure invasive mucinous adenocarcinoma in 99 cases and mixed mucinous/non-mucinous invasive adenocarcinoma in 45 cases.The results of chi-square test and Fisher’s exact probability method showed that the positive expression rate of TTF1 protein in tumor tissues was higher in patients with pleural invasion-positive hypofractionated mucinous adenocarcinoma(86.7%,13/15)than in patients with pleural invasion-negative mucinous adenocarcinoma(58.7%,73/126).2.In this study,we analyzed the histopathological features of 144 patients with mucinous adenocarcinoma of the lung.Along with the general histological features of mucinous adenocarcinoma,we found special pathological structural components in some cases.These included tertiary lymphatic structures,fibrous scarring,and peribronchial hyperplasia.These components were particularly prominent in cases of high-grade mucinous adenocarcinoma.Additionally,in some regions,tumor cells were observed to undergo transitional migration with fine bronchial epithelial cells or grow around the fine bronchial distribution.3.In a study of 144 cases of pulmonary mucinous adenocarcinoma,several markers were found to be expressed including MUC1,MUC4,MUC5 AC,MUC6,TTF1,TFF1,and HNF4 a.Specifically,MUC1 was found to be diffusely expressed in the cell membrane of tumor cells,while MUC5 AC was clearly visible in the cytoplasm of tumor cells.The study found that MUC4 had a positive expression rate of 61.2%(87/142).Interestingly,most of the positive expression sites were in areas with low differentiation of tumor cells,while expression in areas with better differentiation was not significant.Furthermore,the positive staining of MUC4 was higher in the presence of complex glandular or solid-based tumor components and imprinted tumor cell components;the positive expression rate of MUC6 was 35.9%(51/142),we observed that the staining intensity of MUC6 was higher in the more differentiated regions of the tumor compared to the less differentiated regions.And we found that the expression pattern of MUC6 was mutually exclusive with that of MUC4;TTF1 staining was predominantly localized in the nucleus and was diffusely expressed in most cases;TTF1-positive cases showed better morphological differentiation compared to TTF1-negative cases;TFF1 expression was observed in both the nucleus and cell membrane,particularly in papillary structures,but staining intensity was weaker in vesicles,solid,and micropapillary structures;the color development site of HNF4 a was situated within the nucleus of tumor cells;there appears to be no discernible difference in coloration among the various histological types.4.The expression of HNF4 a protein was not significantly correlated with the expression of MUC1 protein,MUC5 AC protein,MUC4 protein,and MUC6 protein.(P>0.05).5.The expression of TTF1 protein was correlated with the expression of MUC5 AC protein,MUC6 protein,MUC4 protein,and TFF1 protein(P<0.05).6.The expression of TFF1 protein was correlated with the expression of mucin MUC5 AC and MUC6(P<0.05).7.Kaplan-Meier(K-Method)survival curve plots showed that the cumulative survival rate was significantly lower in the group of cases with high MUC4 expression than in the group of cases with negative MUC4 protein expression,and the difference was statistically significant(χ2=6.036,P=0.014),Kaplan-Meier(K-Method)survival curves showed that the cumulative survival rate was significantly lower in the MUC4 high expression case group than in the MUC4 negative protein expression case group,and the difference was statistically significant(χ2=6.036,P=0.014),and the cumulative survival rate was significantly lower in the MUC6 negative protein expression case group than in the MUC6 positive protein expression case group,and the difference was statistically significant(χ2=3.972,P=0.046).significant(χ2=3.972,P=0.046).Cox regression analysis revealed that the expression of mucin MUC4(95%confidence interval CI 0.072 to 0.763,P=0.020)and airway dissemination(95%confidence interval CI 0.018 to 0.763,P=0.025)had a significant impact on the prognosis of patients with pulmonary mucinous adenocarcinoma,and the difference was statistically significant.The cumulative survival rate in the HNF4 a protein-positive expression case group was lower than that in the HNF4 a protein-negative expression case group,but the difference was not statistically significant(P>0.05).Similarly,The cumulative survival rate was lower in the TFF1 positive expression group than in the TFF1 negative expression group,and the difference was not statistically significant(P>0.05).The difference between the cumulative survival rate in the TTF1 protein-positive expression group and the TTF1protein-negative expression group was not statistically different(P > 0.05).Conclusion(s):1.Different tissue subtypes of invasive mucinous adenocarcinoma have different immunophenotypes.MUC4 protein,MUC5 AC protein,MUC6 protein,TTF1 protein and TFF1 protein could be used as potential molecular markers to guide the diagnosis of mucinous adenocarcinoma of the lung.2.The prognosis of mucinous adenocarcinoma is related to MUC4 protein and MUC6 protein.Patients with mucinous adenocarcinoma with positive expression of MUC4 protein have a poor prognosis,while patients with mucinous adenocarcinoma with positive expression of MUC6 protein have a better prognosis.The expression of MUC4 protein and airway dissemination factors are independent prognostic factors for the cumulative survival rate of patients with pulmonary mucinous adenocarcinoma..3.The expression of TFF1 and HNF4 a proteins may indicate a poor prognosis for patients with pulmonary mucinous adenocarcinoma.Although the statistical significance is not considerable,the findings suggest the potential value of these proteins as prognostic biomarkers. |
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