Overexpression of Karyopherin α2 in small cell carcinoma of the cervix correlates with poor prognosis.

BACKGROUND: Cervical small cell carcinoma (SCCC) is uncommon and little is known about its molecular markers. Karyopherin α2 (KPNA2) has been demonstrated in a variety of malignancies. Our objective was to determine whether the KPNA2 level is predictive of clinical outcome in patients with SCCC. METHODS: We detected KPNA2 expression by immunohistochemistry in SCCC tumors from 62 patients. The staining results were evaluated by H-score. The correlation among KPNA2 expression level, clinical characteristics, and prognosis was analyzed. RESULTS: KPNA2 expression was detected in tumor tissue from 55 patients with SCCC (55/62, 89%). High KPNA2 expression correlated significantly with International Federation of Gynecology and Obstetrics staging (P=0.035), tumor size (P=0.019), poorer overall survival (OS) (P=0.008), and poorer disease-free survival (P=0.004) compared to low KPNA2 expression. Multivariate analysis showed that KPNA2 expression level (P=0.037) and tumor size (P=0.046) were independent prognostic factors of OS. CONCLUSIONS: KPNA2 may be a molecular marker and indicator of prognosis in SCCC.

Patient with EGFR-mutant lung cancer harboring de novo MET amplification successfully treated with gefitinib combined with crizotinib.

While 50% of lung adenocarcinoma patients in Asia have mutations in the epidermal growth factor receptor (EGFR) site, there are few patients with the EGFR mutation accompanied by de novo mesenchymal-epithelial transition (MET) amplification. Due to the low incidence rate, there is no consensus regarding treatment. Here, a case of a 62-year-old never smoker presented with EGFR Exon19del and de novo MET amplification. A radiographic examination and computed tomography (CT) imaging were conducted on the chest and middle abdomen. A pulmonary puncture was performed and a sample of the lung tissue was used for pathologic diagnosis. Immunohistochemistry was performed for the expression of CK, P40, P63, ttf-1, NapsinA, alk-d5f3, and ki-67 on the cancer cells. Craniocerebral magnetic resonance and whole body bone imaging were completed. Second-generation gene sequencing (next-generation sequencing [NGS]) and fluorescence in situ hybridization examination were also performed to further characterize the cancer cells. A radiographic examination was performed and revealed space-occupying lesions in the lungs. CT results revealed a mass in the upper lobe of the left lung. The pathologic diagnosis was non-small cell carcinoma T3N2M1a. Second-generation gene sequencing (NGS) indicated EGFR Exon 19del (p.E746_A750del, mutant abundance: 13.99%) with de novo MET amplification (CHR: q31.2, CN = 4.0). Fluorescence in situ hybridization examination confirmed MET amplification. Targeted therapy with gefitinib combined with crizotinib was administered as treatment. Four weeks later, the CT results revealed a substantial reduction in the lesion size. The patient was followed up with favorable complete recovery and no tumor-related symptoms. Although crizotinib is efficacious when used alone in follow-up treatment; however, these results of this case and others indicate that it is likely safe to use both drugs together in the case of drug resistance.

Role of Long Noncoding RNA 799 in the Metastasis of Cervical Cancer through Upregulation of TBL1XR1 Expression.

Long noncoding RNAs (lncRNAs) are closely associated with the molecular mechanisms underlying cancer development, and it would be highly useful to study their expression and mechanisms in cervical cancer too. The current study investigated lncRNA799 expression in cervical cancer in order to determine its clinical importance in the progression of cervical cancer. lncRNA799 expression was studied in 218 cervical cancer samples. Expression of lncRNA799 was significantly higher in the cervical cancer tissue than in the adjacent normal tissue. Overexpression of lncRNA799 was found to have a significant correlation with FIGO stage, SCC-Ag level, and lymphatic metastasis, and it was also associated with poor survival. Ectopic expression of lncRNA799 promoted the metastasis of SiHa cells, whereas lncRNA799 knockdown had an inhibitory effect on metastasis. Western blot analysis demonstrated that lncRNA799 promotes the expression of transducing ß-like protein 1-related protein (TBL1XR1), and that lncRNA799 and TBL1XR1 expression show strong correlation in cervical cancer. Moreover, lncRNA799 modulated the expression of TBL1XR1 by acting as a competitive endogenous RNA (ceRNA) for miR-454-3P. The results indicate that lncRNA799 could be used as a novel marker of cervical cancer prognosis. Thus, targeting the ceRNA network involving lncRNA799 could be a potential treatment strategy against cervical cancer.