The Relationship Among EGFR Mutations、histologic Subtypes And The Expression Of TTF-1and SPA In Lung Adenocarcinoma

Background and purposeLung cancer is the leading cause of cancer death worldwide and the incidence of adenocarcinoma of the lung is increasing. For the past few years, the main focus of the lung cancer research concentrated on the subtype of lung adenocarcinoma, especially the EGFR related molecular target therapy. A widely divergent clinical, molecular, and pathologic spectrum exists within lung adenocarcinoma. However, the classifications of lung adenocarcinoma were respectively published by the World Health Organization in2004and the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society in2011. It has been discovered by many foreign researchers that the histologic subtypes is associated with EGFR mutations in lung adenocarcinoma but there is less research in this field at home. This study aimed to explore the associations among EGFR mutations、histologic subtypes and the expression of TTF-1and SPA in lung adenocarcinoma.MethodsIn this study, a total of235lung adenocarcinoma with EGFR testing results (71biopsies and164resections) from January2008to November2011at the Henan province cancer hospital was recruited. For the206HE stainings, histologic subtypes were classified according to both2004World Health Organization classification and2011International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Meanwhile, The TTF-1and SPA expression in the122resected adenocarcinoma specimens were detected by Immunohistochemistry and the correlations among EGFR mutations、 histologic subtypes and the expression of TTF-1and SPA in lung adenocarcinoma were analyzed by SPSS17.0.Results1. Mutations of the EGFR gene were detected in103of the235patients (43.8%). Women and nonsmokers were found to be significantly associated with the incidence of EGFR gene mutations (P<0.001, P=0.002);2. Regarding histologic subtypes of lung adenocarcinoma, the presence of nonmucinous BAC components showed the most frequent EGFR mutations (P=0.012), but mixed mucinous BAC components had lower EGFR mutations (P=0.004); The presence of papillary components was likely to have a high EGFR mutaions, but there was no significant difference (P=0.057); Also, EGFR mutations were more frequently observed in adenocarcinoma with papillary predominant than those with invasive mucinous adenocarcinoma and solid predominant using the new IASLC/ATS/ERS classification (P=0.038);3. Positive immunostaining with TTF-1and SPA was noted in88.0%and62.7%of lung adenocarcinoma and the two had a significant positive correlation (P=0.005); Positive expressing of TTF-1were more frequent in women and nonsmokers (P=0.029, P=0.034);4. The expressing of TTF-1and SPA were significantly associated with EGFR mutations in lung adenocarcinoma (P=0.004, P=0.021), especially the negative predictive value of TTF-1(92.9%).Conclusion 1. The incidence of EGFR mutations is significantly associated with histologic subtypes、 gender and smoking history. The presence of nonmucinous BAC components (lepidic)、papillary predominant、 women or nonsmokers can predict higher EGFR mutation in lung adenocarcinoma but the presence of mucinous BAC components have an inverse relationship;2. As the specific immunohistochemical markers in lung adenocarcinoma, TTF-1and SPA have significant positive correlation. Also, positive TTF-1staining is found to be significantly associated with women and nonsmokers;3. TTF-1and SPA immunohistochemical staining can predict EGFR mutation in lung adenocarcinoma especially the negative predictive value of TTF-1.