Clinical application of the 2011 IFCPC colposcope terminology.

BACKGROUND: Colposcopy offers an accurate way to the diagnose of cervical precancerous lesions. However, the diagnostic accuracy of colposcopy is unsatisfied. This study was to evaluate colposcopic accuracy according to the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) terminology. METHODS: A retrospective cohort study was performed in 1,838 patients who underwent colposcopy in Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University from October 2013 to April 2018. Using conization or cervical biopsy pathology as the gold standard, the agreement between colposcopic diagnosis and pathologic diagnosis was calculated, and correlations between variables were analyzed. RESULTS: As an authoritative and widely used terminology for colposcopy diagnosis, the 2011 IFCPC terminology has certain clinical practicality and diagnostic accuracy. However, some signs such as mosaic, punctation, sharp border, inner border sign and ridge sign had high specificity but unsatisfactory sensitivity, which limited the diagnostic value. Therefore, we discussed the Lugol's staining, a very common sign in colposcopy, and analyzed the diagnostic significance of bright yellow staining in low-grade squamous intraepithelial lesion (LSIL) and mustard yellow staining in high-grade squamous intraepithelial lesion (HSIL). The results showed that mustard yellow may be a valuable indicator in the diagnosis of HSIL. CONCLUSION: The 2011 IFCPC colposcope terminology has standardized interpretations of the colposcopic findings and improved the accuracy of colposcopy diagnosis. The aceto-white epithelium still has important diagnostic value; however, the value of a few signs is needed to be discussed and new signs are expected to be discovered. Although the significance of Lugol's staining was diminishing, mustard yellow might be a valuable indicator for the diagnosis of HSIL.

Tubal Origin of "Ovarian" Low-Grade Serous Carcinoma: A Gene Expression Profile Study.

OBJECTIVE: Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, serous cystadenomas, and serous borderline tumors. Our previous study with clinicopathological approach showed that the majority ovarian epithelial inclusions are derived from the fallopian tubal epithelia rather than from ovarian surface epithelia. This study was designed to gain further insight into the cellular origin of ovarian low-grade serous carcinomas by differential gene expression profiling studies. METHODS: Gene expression profiles were studied in 43 samples including 11 ovarian low-grade serous carcinomas, 7 serous borderline tumors, 6 serous cystadenomas, 6 ovarian epithelial inclusions, 7 fallopian tubal epithelia, and 6 ovarian surface epithelia. Comprehensive analyses with hierarchical clustering, Rank-sum analysis and Pearson correlation tests were performed. Final validation was done on selected genes and corresponding proteins. RESULTS: The gene expression profiles distinguished ovarian low-grade serous carcinomas from ovarian surface epithelia, but not from fallopian tubal epithelia cells. Hierarchical clustering analysis showed ovarian serous tumors and ovarian epithelial inclusions were clustered closely in a branch, but separated from ovarian surface epithelia. The results were further validated by selected proteins of OVGP1, WT-1, and FOM3, which were highly expressed in the samples of the fallopian tube, ovarian epithelial inclusions, and ovarian serous tumors, but not in ovarian surface epithelia. The reverse was true for the protein expression patterns of ARX and FNC1. CONCLUSIONS: This study provides evidence in a molecular level that ovarian low-grade serous carcinomas likely originate from the fallopian tube rather than from ovarian surface epithelia. Similar gene expression profiles among fallopian tube, ovarian epithelial inclusions, and serous tumors further support that ovarian low-grade serous carcinomas develop in a stepwise fashion. Such findings may have a significant implication for "ovarian" cancer-prevention strategies.

53BP1 inhibits the migration and regulates the chemotherapy resistance of ovarian cancer cells.

The major problems faced during the treatment of ovarian cancer are metastasis and the development of intrinsic or acquired drug resistance. The present study assessed whether tumor protein p53 binding protein 1 (53BP1) regulated migration and modulated chemotherapy resistance in SKOV3 cells and identified proteins associated with the molecular mechanisms underlying this coordinate regulation. SKOV3 cells were transfected using a 53BP1-expressing vector, which induced 53BP1 overexpression. The migration of the transfected cells was observed using a Transwell assay. The expression of matrix metalloproteinase (MMP)-2 and MMP-9 were assayed using gelatin zymography. In addition, the effects of 53BP1 on the chemosensitivity of SKOV3 cells to cisplatin were evaluated using MTT and western blot assays. Compared with the control, the average number of migrating SKOV3/pLPC-53BP1 cells was decreased from 230±58 to 45±12 (P<0.05) and the protein expression of MMP-9 was significantly inhibited. However, the chemosensitivity of SKOV3/pLPC-53BP1 to cisplatin decreased significantly: Cisplatin half maximal inhibitory concentration (IC50) for SKOV3/pLPC-53BP1=7.58±0.51 µg/ml; cisplatin IC50 for control=2.98±0.27 µg/ml (P<0.01). Decreased chemosensitivity to cisplatin may be associated with increased expression of phosphorylated-protein kinase B and cyclin dependent kinase 2 and with decreased expression of p21 and the B cell lymphoma (Bcl)-2 associated X/Bcl-2 ratio. The results of the present study demonstrated that 53BP1 may inhibit migration but upregulate chemoresistance to cisplatin in SKOV3 cells.

Malignant Female Adnexal Tumor of Probable Wolffian Origin: Case Report and Literature Review.

Although most female adnexal tumors of probable Wolffian origin have a benign biologic behavior, occasional cases have exhibited malignant potential. We encountered a 50-yr-old woman with an uncommon female adnexal tumors of probable Wolffian origin, which involved bilateral ovaries, invaded the ipsilateral fallopian tube, and extended to the uterine serosa. The initial histopathologic presentation caused significant confusion in pathologic diagnosis. Multiple differential diagnoses including ovarian endometrioid carcinoma, Sertoli cell tumor, and metastasis from nongynecologic organs were considered. After careful examination of the histologic findings and a thorough investigation with multiple immunohistochemical stains, the diagnosis was ultimately established. A literature review on female adnexal tumors of probable Wolffian origin including a malignant form is presented.

BRCA1 expression, proliferative and apoptotic activities in ovarian epithelial inclusions.

BACKGROUND: The purpose of this study was to examine proliferative and apoptotic activity in relation with BRCA1 expression in ovarian epithelial inclusions (OEIs), the putative precursor lesions of ovarian epithelial cancer (OEC). METHODS: Benign ovaries from 95 patients were examined. Dual immunohistochemical staining for both BRCA1 and MIB-1 were performed to examine the relationship between BRCA1 and MIB-1 in OEI cells. Apoptotic activity was assessed on the parallel tissue sections by using TUNEL assay. Patients' age, menstrual phase and menopausal status were analyzed. RESULTS: OEIs were present in the ovaries of 53% of the patients. OEIs were less frequently found in premenopausal (45%) than postmenopausal women (58%). BRCA1 and MIB-1 were found in 27 and 47% of the OEI-containing ovaries, respectively. All BRCA1 positive OEI cells are MIB-1 positive with dual staining method, although overall the percentage of positive cells was small. No significant difference was found for BRCA1 and MIB-1 expression in OEIs between menopausal status and menstrual phases. Apoptosis containing OEIs were seen in 70% of the ovaries. Compared to OEIs in proliferative menstrual phase and premenopausal status, significantly more apoptosis was found in OEIs from secretory phase and postmenopausal women. A small fraction of the epithelial cells within OEIs are proliferating or dying. CONCLUSIONS: Low estrogen and/or high progesterone levels may promote OEI cell turnover via induction of apoptosis. Imbalance between cell proliferation and death within OEIs under influence of hormones may play a role in the ovarian epithelial tumorigenesis.

Alterations in the serum proteome profile during the development of ovarian cancer.

Ovarian cancer causes more deaths than any other malignant tumor of the female reproductive system. This is because the condition usually goes undetected until the late stages. The purpose of the present study is to identify alterations in the serum proteome profile during the development of ovarian cancer and to provide an experimental basis for discovering new and valuable serum biomarkers for the early detection of ovarian carcinoma. Surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF-MS) was used to profile changes in the serum proteome of Fischer 344 rats with ovarian cancer during the progress of tumor development. Sera were collected from the rats on day A (1 week before injection of tumor cells), day B (4 weeks after injection), and day C (6 weeks after injection). Each sample was subjected to SELDI-TOF-MS testing. Peak detection and alignment and selection of peaks with the highest discriminatory power were performed using proteinchip biomarker software. Decision tree analyses were performed using biomarker pattern software. Finally, 3 peaks were found to be the most valuable ones (3759, 4659 and 9318 Da). The expression frequency of m/z 3759-Da peaks was downregulated and another two frequencies (4659 and 9318 Da) were upregulated, and the levels of expression of these three proteins showed the same tendency as the expression frequency during the development of ovarian cancer. The total accuracy rate of diagnosis at 4 and 6 weeks post-injection was 94.7 and 97.3%, respectively. Profiling the serum proteome changes during the process of the cancer development using SELDI-TOF-MS may provide useful information regarding carcinogenesis and facilitate discovery of novel serum biomarkers for early detection.

Enforced effect of tk-MCP-1 fusion gene in ovarian cancer.

OBJECTIVE: The efficiency of HSV-tk/GCV system is not high because of insufficient gene transfer and incompletely initiative of host antineoplastic potency. The present study was designed to assess the antitumor efficacy of tk-MCP-1 on ovarian cancer in vitro and vivo. METHODS: A novel bicistronic expression system can help to improve the expression level of a gene in a stable manner. pLXSN/tk-MCP-1 co-expressing tk and MCP-1 genes was constructed using a pLXSN retroviral vector and an internal ribosome entry site sequence by restriction enzyme. Western blot was performed to determine tk and MCP-1 expression in the infected SKOV3. The GCV-sensitively tumoricidal activities of SKOV3/tk-MCP-1 with or without monocytes were compared to those of SKOV3 expressing HSV-tk or MCP-1. We investigated the growth of subcutaneous tumors in SCID mice immuno-reconstituted, and evaluated the antitumor effect of MCP-1 in conjunction with suicide gene. RESULTS: The significant GCV-sensitively tumoricidal activity of pLXSN/tk-MCP-1 was observed when compared with those of pLXSN/tk, pLXSN/MCP-1 and pLXSN/neo, especially when monocytes were added. The growth of subcutaneous tumors in SCID mice immuno-reconstituted was markedly suppressed by co-delivery of HSV-tk and MCP-1 genes, and the enhanced antitumor effect was associated with the recruitment of monocytes. CONCLUSION: These results demonstrated pLXSN/tk-MCP-1 presented an enhanced antitumor effects on ovarian cancer by orchestration of immune responses.

Metadherin regulates radioresistance in cervical cancer cells.

Metadherin (MTDH) promotes cancer metastasis, chemoresistance, invasion and angiogenesis. Upregulation of MTDH is correlated with both progression and poor clinical outcome of many types of cancers; however, there is currently no information regarding the role of MTDH in radiation sensitivity. Here, we investigated the effects of MTDH on the radiosensitivity of cervical cancer cells using the SiHa cell line. We discovered that cervical cancer cells in which MTDH was knocked down had significantly increased radiosensitivity as measured by a clonogenic assay. MTDH knockdown cells also had increased apoptosis and a decreased proportion of cells arrested in the G2 phase after radiation treatment. MTDH knockdown also weakened the repair of DNA double-strand breaks (DSBs) induced by radiation. These results indicate that MTDH affects the radiosensitivity of cervical cancer cells and that MTDH may be a novel target to improve cervical cancer radiation response.

53BP1 suppresses tumor growth and promotes susceptibility to apoptosis of ovarian cancer cells through modulation of the Akt pathway.

53BP1 has been extensively studied as a key component of the DNA damage response, but little is known regarding the role of 53BP1 in preventing tumor development. The present study was designed to assess the impact of the modification of 53BP1 gene expression on the biological behavior of ovarian cancer cell lines and to elucidate the cellular pathway(s) triggered by 53BP1 in cancer cells. DNA liposome transfection technology was employed to increase and to knock down the expression of 53BP1 in A2780 and HO-8910PM cells, respectively. Viability, clonogenicity and cell cycle profiles were evaluated. Cell apoptosis was analyzed using flow cytometric assay. The expression of proteins related to apoptosis and cell signal transduction was assessed using western blotting. Increased expression of 53BP1 decreased the viability and the clonogenicity, and induced G2/M arrest and apoptosis of the treated cells. The protein expression of Bax, P21 and caspase-3 was upregulated, while the levels of Bcl-2 and p-Akt were reduced to a statistically significant level. In contrast, deregulation of 53BP1 significantly increased proliferative ability. Collectively, our data suggest that 53BP1 is involved in several important steps in controlling cell proliferation and growth and preventing tumor development.

Comparison of laparoscopy and laparotomy for endometrial cancer.

OBJECTIVE: To compare the safety and efficacy of laparoscopy and laparotomy on clinical outcomes among patients with endometrial cancer. METHODS: Eligible randomized controlled trials (RCTs) conducted between 1966 and June 2010 were analyzed by meta-analysis. RESULTS: Eight RCTs were included, with 3599 patients in total. No significant difference was observed between laparoscopy and laparotomy in overall (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.50-1.82; P=0.892), disease-free (OR, 0.96; 95% CI, 0.50-1.82; P=0.892), or cancer-related (OR, 0.90; 95% CI, 0.27-3.08; P=0.871) survival. More intraoperative complications (OR, 1.33; 95% CI, 1.03-1.73; P=0.030), fewer postoperative complications (OR, 0.59; 95% CI, 0.46-0.75; P<0.001), longer operative time (standardized mean difference [SMD], 0.80; 95% CI, 0.46-1.15; P<0.001), lower blood loss (SMD, -2.29; 95% CI, -3.67 to -0.91; P=0.001), and shorter hospital stay (SMD, -2.60; 95% CI, -3.47 to -1.72; P<0.001) were associated with laparoscopy. There was no significant difference between the groups in pelvic (SMD, 0.22; 95% CI, -0.03 to 0.48; P=0.086) or para-aortic (SMD, 0.54; 95% CI, -0.04 to 1.11; P=0.067) lymph node yield. CONCLUSION: Laparoscopy has short-term advantages and seemingly equivalent long-term outcomes and, in experienced hands, might be a feasible alternative to laparotomy for endometrial cancer.

Parkinson's disease: functional changes in frontal and parietal cortex using 18 F- fluoro-deoxy glucose positron emission tomography/computed tomography.

BACKGROUND: In Parkinson's disease (PD) there is increasing evidence to suggest motor function changes of the cerebral cortex occur in addition to the pathological changes in the extrapyramidal system. AIMS: To explore the functional changes in the frontal and parietal cortex in PD cat model. SETTINGS AND DESIGN: Twenty-four healthy male cats were divided into four animal model groups with the injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), and one control group. MATERIALS AND METHODS: Cats in both the animal model and control groups were observed for the behavioral changes. They were also examined by 18 F-fluoro-deoxy glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). Region of Interest (ROI) was determined by 18 F-FDG intensity and semi-quantitative analysis was employed after detecting the standard absorption value (SUV). Statistical Analysis : Statistical significance was evaluated by ANOVA. RESULTS: Compared to control group, the 18 F-FDG intensity and SUV were found normal on both the sides of frontal and parietal cortex in the PD models on the second day (P > 0.05), and on the fifth day, they were reduced significantly on both the sides of frontal cortex exclusively (P < 0.05). Moreover on the eighth day, the SUV of both frontal cortexes was reduced, while it was increased in both parietal cortex (P < 0.05). Finally on the eleventh day, the SUV remained stable in both the frontal cortex, and was back to normal level in both the parietal cortex. CONCLUSIONS: Functional disorders exist in the frontal cortex of PD animals and aggravate with time. Transient functional enhancement in the parietal cortex of PD cats might be a compensation for the dysfunction of frontal cortex.

Functional changes in the frontal cortex in Parkinson's disease using a rat model.

In recent years, investigations of the pathologic mechanism of Parkinson's disease (PD) have mainly concentrated on the basal ganglia. However, recent studies have confirmed that pathological changes in PD are accompanied by functional motor changes of the cerebral cortex. Rats were injected with 6-hydroxydopamine and ascorbic acid in the right substantia nigra. In this rat model of PD, magnetic resonance spectroscopy showed the ratio of N-acetyl-aspartic acid to creatine in a lesion in the right frontal cortex was significantly lower than the same ratio in a control group of rats. The ratio of choline to creatine in a lesion in the right frontal cortex was not significantly different between the PD-model rats and control rats. In addition, the optical densities of neurofilament protein and synaptophysin positive sites decreased significantly on the side of the brain with the injury compared with the side without the injury, and with both sides in the control rats. The density of synapses in the frontal cortex on the lesioned side was decreased compared with the unlesioned side. There were abnormal changes in the presynaptic membrane, postsynaptic membrane and synaptic vesicles, and the typical synaptic structure was no longer apparent on the lesioned side. We hypothesized loss of neurons and synapses, abnormal synaptic structure and neuron and synaptic dysfunction of the frontal cortex with a lesion in the injury side of the frontal cortex in PD-model rats. These changes might have an important role in the pathologic mechanism of PD.