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Background: Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown., Methods: In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled. HPV DNA and HPV types were detected using the hybrid capture-2 HPV DNA test. Flow cytometry was used to investigate iNKT and CD3+ T cell infiltration into cervical tissues. Real-time quantitative reverse transcription-polymerase chain reaction was used to study IFN-γ expression and immunohistochemistry was used to determine CD3+ T cell distribution., Results: A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01). IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05). CD3+ T cells were detected among both epithelium and stromal layers in cervical tissues, and the percentage of CD3+ T cells in HPV-positive cervical tissues was similar to that in HPV-negative cervical tissues (p > 0.05)., Conclusions: The iNKT cell aggregation in cervical tissues during the progression from HPV infection to CIN indicates that iNKT cells might play an important role in suppressing immunity. IFN-γ expression could also be related to the HPV infection status. Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN., Virtual Slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2521874671514142.

Background: As an acute-phase protein, serum amyloid A (SAA) is expressed primarily in the liver. However, its expression in extrahepatic tissues, especially in tumor tissues, was also demonstrated recently. In our study, we investigated the expression of SAA in uterine cervical carcinomas, and our results suggested its potential as a serum biomarker., Methods: Quantitative real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the SAA gene and protein expression levels in the tissues and sera of patients with non-neoplastic lesions (NNLs), cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC)., Results: Compared with NNLs, the SAA gene (SAA1 and SAA4) expression levels were significantly higher in uterine CC (mean copy numbers: 138.7 vs. 5.01, P < 0.000; and 1.8 vs. 0.079, P = 0.001, respectively) by real-time PCR. IHC revealed cytoplasmic SAA protein staining in tissues from adenocarcinoma and squamous cell carcinoma of the cervix. The median serum concentrations (μg/ml) of SAA were 6.02 in patients with NNLs and 10.98 in patients with CIN (P = 0.31). In contrast, the median serum SAA concentration was 23.7 μg/ml in uterine CC patients, which was significantly higher than the SAA concentrations of the NNL group (P = 0.002) and the CIN group (P = 0.024)., Conclusions: Our data suggested that SAA might be a uterine CC cell product. High SAA concentrations in the serum of CC patients may have a role in monitoring disease occurrence and could have therapeutic applications., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1433263219102962.

Background: Ubiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X). Recent evidence indicates that USP9X is involved in the progression of various human cancers. The aim was to detect the expression of USP9X in the progression from normal epithelium to invasive esophageal squamous cell cancer (ESCC) and evaluate the relevance of USP9X expression to the tumor progression and prognosis., Methods: In this study, USP9X immunohistochemical analysis was performed on tissues constructed from ESCC combined with either normal epithelium or adjacent precursor tissues of 102 patients. All analyses were performed by SPSS 13.0 software., Results: We observed that the level of high USP9X expression increased gradually in the transformation from normal epithelium (4.0%), to low grade intraepithelial neoplasia (10.5%), then to high grade intraepithelial neoplasia (28.6%), and finally to invasive ESCC (40.2%). The expression of USP9X was found to be significantly different between the normal mucosa and ESCC (P < 0.001), and between low grade intraepithelial neoplasia and high grade intraepithelial neoplasia (p = 0.012). However, no difference was observed between the high expression of USP9X in normal mucosa and low grade intraepithelial neoplasia (P = 0.369), nor between high grade intraepithelial neoplasia and ESCC (p = 0.115). Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion. USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032). Increased USP9X expression was significantly correlated to poorer survival rate in ESCC patients (p = 0.001). When adjusted by multivariate analysis, USP9X expression (HR 2.066, P = 0.005), together with TNM stage (HR 1.702, P = 0.042) was an independent predictor for overall survival., Conclusions: Up-regulation of USP9X plays an important role in formation and progression of precancerous lesions in ESCC and USP9X expression levels were significantly correlated with the survival of ESCC patients. Thus, USP9X could be considered as a potential biomarker and prognostic predictor for ESCC., Virtual Slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1945302932102737.

Background: Intraperitoneal (i.p.) models that accurately mimic the feature behavior of human ovarian cancer are required to investigate the pathology and therapeutics of the disease. However, established i.p. models which are well-characterized and reliable are few. The purposes of this study are to establish a representative mice i.p. model of the disease and to analyze the consequent pathology., Methods: Fresh tumor cells fiom the ascites of patient were injected into female NOD/SCID mice intraperitoneally. Histology, Cytogenetic, immunohistochemistry,tumor markers of CA125,AFP, CA-199 and CEA were used to analyze the model., Results: The mice developed marked abdominal distention within 6 months after inoculated with tumor cells from a patient with epithelial ovarian carcinoma. The mice developed clinically evident intraperitoneal tumors and massive ascites containing numerous tumor cells in clumps. CA125 level in our model was high in both serum and ascites supernatants, while levels of other tumor markers, such as AFP, CA-199 and CEA, were normal. Cytogenetic analysis and immunohistochemical staining confirmed its characteristics resembling human epithelial ovarian tumor., Conclusions: The model described in this paper accurately mimics the features of ovarian tumor, which may be useful for evaluation of new therapeutics.

Background: Human papillomavirus (HPV) infection plays an etiological role in the development of cervical dysplasia and cancer. Amplification of human telomerase gene (hTERC) and over expression of telomerase were found to be associated with cervical tumorigenesis. This study was performed to analyze genomic amplification of hTERC gene, telomerase activity in association with HPV infection in different stages of cervical intraepithelial neoplasia (CIN) and cervical cancer. We were studying the role of hTERC in the progression of uterine cervical dysplasia to invasive cancer, and proposed an adjunct method for cervical cancer screening., Methods: Exfoliated cervical cells were collected from 114 patients with non neoplastic lesion (NNL, n=27), cervical intraepithelial neoplasia (CIN1, n=26, CIN2, n=16, CIN3, n=24) and cervical carcinoma (CA, n=21), and analyzed for amplification of hTERC with two-color fluorescence in situ hybridization (FISH) probe and HPV-DNA with Hybrid Capture 2.From these patients, 53 were taken biopsy to analyze telomerase activity by telomeric repeat amplification protocol (TRAP) and expression of human telomerase reverse transcriptase (hTERT), with immunohistochemistry (IHC). All biopsies were clinically confirmed by phathologists., Results: Amplification of hTERC was significantly associated with the histologic diagnoses (p<0.05). The positive correlation was found between the level of hTERC amplification and histologic grading of dysplasia (CIN2/3 from CIN1 or normal, P=0.03). A profounding increase in the accumulation of HPV and hTERC positive cases was observed in the CIN3 subgroup compared with the CIN2 group, 25% versus 62.96%, respectively (p=0.007)., Conclusions: hTERC ampliffication can be detected with FISH technique on exfoliated cervical cells. Amplification of hTERC and HPV infection are associated with more progressive CIN3 and CA. The testing of hTERC amplification might be a supplementary to cytology screening and HPV test, especially high-risk patients., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1857134686755648.