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Purpose: Although the mortality of elderly women with cervical cancer is high, their characteristics and prognosis have not attracted sufficient attention. This study aims to clarify the prognostic factors of cervical cancer patients aged ≥65. Patient and Methods: The incidences and characteristics of patients diagnosed with cervical cancer (aged ≥65 and <65) during 2004-2015 were obtained through the Surveillance, Epidemiology, and End Results Program (SEER) database. The differences of distributions of characteristics between two age groups were compared by chi-squared (χ 2 ) test. Kaplan-Meier survival method, Log-rank test, Cox-regression and visual nomogram were utilized for survival analysis. Results: The annual incidences of two age groups with cervical cancer were (5.5-7.5)/100,000 and (3.4-3.9)/100,000, respectively, during 2004-2015. The 1-year and 5-year cancer-specific survival rates of old patients were both lower than those of young patients (P <0.001). The proportions of unmarried state and advanced International Federation of Gynecology and Obstetrics (FIGO) stage in old patients were higher than those in relatively young patients, and fewer elderly patients received surgery. Univariate and multivariate survival analysis showed nonsquamous cell carcinoma, poor differentiation and late FIGO stage were independent poor prognostic factors for patients aged ≥65. Treatments improved the outcomes of elderly patients, and the effect of surgery was better than non-surgical treatment on elderly patients with FIGO I. Besides, geriatric score and survival probability could be accomplished by our nomogram with a c-index of 0.7945. Conclusion: Delayed diagnosis and insufficient treatment were two distinct features of elderly patients and correlated with their poor clinical outcomes. More attention and active treatments should be adopted in elderly women based on their general condition.

Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.

Altered expressions of receptor for advanced glycation end-products (RAGE) and its ligand (S100A9) are observed in many cancers and play a key role in inflammation-associated cancer. In our previous study, by two-dimensional gel electrophoresis followed by mass spectrometry, the expression of S100A9 protein was found to increase in squamous cervical cancer compared with adjacent normal cervical tissues. Therefore, in the present study we observed the expressions of S100A9 and RAGE in 30 chronic cervicitis, 50 cervical intraepithelial neoplasia (CIN), and 40 squamous cervical cancer (SCC) using immunohistochemical analysis and analyzed the differential expression and possible role of S100A9 and RAGE in cancer development. Immunohistochemical findings were as follows: the expressions of S100A9 and RAGE were demonstrated in chronic cervicitis, CIN, and SCC. Moreover, their expressions were gradually increasing as the tumor progressed. In SCC, the staining scores of S100A9 and RAGE were significantly higher in well-differentiated tumors compared to moderately and poorly differentiated tumors. The expression of S100A9 in epithelial cells exhibited a positive correlation to RAGE expression in chronic cervicitis, CIN, and SCC. There were no significant difference of S100A9 immunoreactivity in stromal cells among chronic cervicitis, CIN, and SCC. Moreover, there was no correlation between S100A9 immunoreactivity in stromal cells of SCC and clinicopathological parameters. Finally, double immunohistochemistry illustrated that RAGE and S100A9 co-express in SCC. In conclusion, RAGE binds its ligand (S100A9), which plays an important role in the development of SCC. In addition, the expressions of S100A9 and RAGE in SCC tumor cells were closely associated with histological differentiation.

Objective: The aim of this study was to investigate the effect of neoadjuvant chemotherapy (NAC) on the human squamous cervical cancer using proteomics profiling and to obtain related proteins to NAC exposure and response. Methods: Paired samples of early-stage bulky squamous cervical cancer before and after NAC treatment from patients who responded to NAC were obtained and submitted to 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS). The expression and localization of the interesting proteins in additional paired samples were confirmed by Western blot analysis and immunohistochemistry. Results: The comparison of the proteins present before and after NAC revealed that 116 protein spots were significantly changed. In all, 31 proteins were analyzed by MS, and 15 proteins were upregulated in the cancer tissue after NAC relative to the level before NAC, whereas 16 proteins were downregulated after NAC. The significantly higher expression of peroxiredoxin 1 and significantly lower expression of galectin 1 after NAC treatment were confirmed by Western blot. Conclusions: Proteomics can be used to identify the NAC-related proteins in squamous cervical cancer. The change in proteins may be associated with NAC exposure and response, but insight into their relevance requires further study.

A uterine tumor resembling an ovarian sex cord tumor (UTROSCT) is a rare type of neoplasm that is almost thoroughly differentiated towards ovarian sex cord elements. Because of abnormal uterine bleeding, a 64-year-old postmenopausal woman received total abdominal hysterectomy with bilateral salpingo-oophorectomy. Under a microscope, the tumor cells showed an anastomosing fascicular and trabecular pattern with a reticular architecture. Immunohistochemistry showed that the tumor cells were positive for calretinin, Wilm’s tumor-1, and vimentin. A 33-year-old woman who suffered from menorrhagia, and was treated for bilateral salpingectomy, total abdominal hysterectomy, and bilateral ovarian biopsy, was also studied. Using histology, the patient was diagnosed with UTROSCT as shown by CD99, smooth muscle actin, calretinin, vimentin, and desmin expression. As a type of rare uterine tumor, UTROSCT can be diagnosed based on morphological and immunohistochemical conditions. Generally, these tumors are benign, but can easily relapse through incomplete resection. Hysterectomy should be performed after completion of family planning.