| Objectives Patients with lung adenocarcinoma have benefited widely from the use of targeted therapy in recent years. Whilst targeted treatment options are still limited in squamous cell lung cancer. With advances in the molecular profile of squamous cell cancers, potential molecular targets including EGFR, PIK3 CA, and PTEN have been identified as key mutant drivers. In this study, 1 we investigated histological and clinical data of 50 patients with central airway squamous cell cancer in China Meitan hospital and aimed to analysis the frequency of epidermal growth factor receptor(EGFR) mutations in exons 18, 19, 20 and 21, PIK3 CA mutations in exons 9 and 20, and discuss the relations between the above mutations and clinical measurements(including gender, age, smoke, pathological stage, differentiation level, and lymphatic metastasis). 2 Explore the presence of exon 10 deletions of PTEN, and the correlations with clinical features.Methods In this study, 1 tissue samples of 50 patients with central airway squamous cell carcinoma were collected in the department of oncology at China Meitan hospital, between June 2009 and December 2013. The presence of DNA mutations in EGFR exons 18-21, and PIK3 CA exons 9 and 20, was detected with PCR and direct sequencing. 2 Fifty samples of tumor and 13 samples of adjacent tissue, were collected from 50 patients with central airway squamous cell carcinoma, in the department of oncology at China Meitan hospital between May 2009 and July 2013. Meanwhile, tissue samples and clinical profiles of 10 patients with pulmonary squamous papilloma were also investigated. The expression of mutations in PTEN was detected by immunohistochemistry(Streptavidin Peroxidase con-jugated method, SP). The expression levels of PTEN protein in above samples were compared. 3 And we discussed the correlations between EGFR, PIK3 CA mutations, PTEN expression and clinical characters including age, gender, pathological stage, differentiation level, and lymphatic metastasis.Results 1 The mutation rates in EGFR and PIK3 CA were 18%(9/50) and 50%(25/50), respectively. Among them, no mutations were detected in EGFR exons 18, 19 and 21. While all 9 EGFR mutations were found in exon 20, mainly at A1634C(E545A). The mutations at G1633A(E545K) or C1616A(P539H) were rare, only found in 1 sample respectively. Within the 9 EGFR mutations, 5 were detected mutations in PIK3CA(55.6%). 2 PTEN expressions were decreased in 50 samples of central airway squamous carcinoma, while high expressionwere found in adjacent tissues and pulmonary squamous papilloma tissues. The expression rate of PTEN was lower in airway squamous cell carcinoma(20.00%) than in adjacent tissues(80.00%) or in benign pulmonary tumors(92.00%), and the difference was statistically significant(χ2=23.542, P <0.010). 3 There is a statistically positive correlation between EGFR gene mutation status and age, differentiation, stage and lymphatic metastasis, in squamous cell lung cancers(P<0.05), while negative correlation with gender or smoke. We showed negative correlations between PIK3 CA mutation and age, gender, smoke, pathological stage, tissue differentiation level or lymphatic metastasis(P>0.05). There is a statistically positive correlation between PTEN protein expression and tumor differentiation levels and lymphatic metastasis(P<0.05), while statistically negative correlation with age, gender, or pathological stage(P>0.05).Conclusions 1 With the research of the correlation between mutations and clinical features, we might provide evidence in exploring potential therapeutic targets like EGFR or PIK3 CA in squamous carcinomas. 2 Our data revealed mutational inactivation of PTEN was related to high malignant degree and metastatic potential. PTEN deletion could be one of measurements of tumor malignancy, and a independent factor of outcome. |
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