[Effectiveness of Different Testing Strategies Applied for Cervical Cancer Screening in Shuangliu District, Chengdu City].

Objective: To evaluate the clinical value of different combination strategies of high-risk HPV (hr-HPV) testing and Thinprep cytology test (TCT), a cervical cytology test, for cervical cancer screening, especially for high or higher-grade squamous intraepithelial lesion (HSIL+) in Shuangliu District, Chengdu City. Methods: The study is a population-based randomized clinical trial. Women aged 35 to 65 years meeting the inclusion criteria were enrolled for the study. At the baseline screening conducted in the first year, the participants were randomly assigned to either cytology test or hr-HPV testing at a ratio of 1∶2. If the paticipants had positive results for the baseline hr-HPV test, they would then undergo either cytology test or colposcopy by random assignment. After 24 months, all participants were called back, and combined screening of cytology test and hr-HPV test were performed. Women who had negative results at baseline screening and who entered and completed the third-year follow-up were selected as the subjects of the study. Based on the aforementioned testing findings, the related data were extracted and four different screening protocols were simulated: 1) combined TCT and hr-HPV screening, with referral for colposcopy when there was positive results for either one of the two; 2) combined TCT and hr-HPV screening, with referral for colposcopy when both tests had positive results at the same time; 3) TCT was done for preliminary screening and those who were found to be positive would then undergo hr-HPV test for triage purpose, with subsequent referral made for colposcopy if the hr-HPV results were positive; 4) hr-HPV was done for preliminary screening and those who were found to be positive would then undergo TCT, with subsequent referral made for colposcopy if TCT results were positive. With the detection of HSIL+ on histological examination as the endpoint event, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve ( AUC) of different combination screening models were calculated. Results: A total of 3102 women were screened, and 2967 women were included in the statistical analysis in this study. Among the 2967 women, 979 were randomized to cytology and 1988 to hr-HPV genotyping. For prescreening, the positive rate of the cytology group was 5.6% (55/979), with of HSIL+ positive rate being 0.2% (2/979), while the positive rate of the hr-HPV group was 7.5% (149/1988), with HSIL+ positive rate being 0.9% (18/1988). After 24 months, 2456 women were called back and were given cervical cytology test and hr-HPV test at the same time. Among them, the positive rate of the cytology group was 3.2% (78/2456), while the positive rate of hr-HPV group was 8.7% (215/2456). The overall positive rate of HSIL+ was 0.69%(17/2456). Women with a negative baseline hr-HPV had a lower incidence of HSIL+ lesions in the long term. The strategy of cervical cytology screening combined with hr-HPV test for triage purpose is the best method, with a sensitivity of 88.9%, a specificity of 58.3%, a PPV of 44.4%, a NPV of 93.3%, and an AUC of 0.736, P=0.039 (95% CI: 0.555-0.917). Conclusion: This randomized clinical trial from Shuangliu District, Chengdu City shows that the sensitivity of hr-HPV testing is better than that of cytology test, and the prevalence of HSIL+ in women with negative baseline hr-HPV results is lower than that of women with negative baseline cytology results. The screening program of TCT for prescreening plus subsequent hr-HPV test for triage purpose shows better value for the detection of HSIL+.

[The Clinical Significance of HPV L1/PD-L1 Tests Combined with Colposcopy for Cervical Precancerous Lesions and Cervical Cancer].

OBJECTIVE: To explore the expression of human papilloma virus (HPV) L1 protein and programmed cell death ligand-1 (PD-L1) protein in cervical precancerous lesions and cervical cancer, to analyze the correlation between HPV L1 and PD-L1 expression tests combined with colposcopy and the occurrence and development of of cervical lesions, and to determine the significance of the combined examination for auxiliary differential diagnosis. METHODS: 260 patients with high-risk HPV (HR-HPV) infection who were treated at West China Second University Hospital, Sichuan University from January, 2018 to January, 2020 were included in the study. 260 cervical cytology specimens were collected, of which 218 cervical histology specimens were collected, of which 202 cases underwent colposcopy. Among the 260 cervical cytology specimens, 40 were of cervical inflammatory cells, 40 were of low-grade squamous intraepithilia lesions (LSIL) with mild atypical hyperplasia, 80 were of high-grade squamous intraepithilia lesions (HSIL) with moderate and severe atypical hyperplasia, and 100 were of cervical carcinoma cells (CCC). Among the 218 cervical histology specimens, 15 were of chronic cervicitis tissue, 20 were of cervical intraepithelial neoplasia (CIN) 1, 32 were of CIN 2, 51 were of CIN 3, and 100 were of cervical cancer (CC). Among the 260 patients, 202 underwent colposcopy. Immunocytochemistry and immunohistochemistry were used to assess the expression of HPV L1 protein and PD-L1 protein, and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess the level of PD-L1 mRNA in chronic cervicitis tissues and CC. The sensitivity, specificity, positive predictive value and negative predictive value of HPV L1 and PD-L1 tests combined with colposcopy in the detection of cervical lesions were studied. RESULTS: ①In the cervical cytology group, the positive rate of HPV L1 expression was 82.50%, 57.50%, 11.25%, and 3.00% in cervical inflammatory cells, low-grade squamous intraepithilia lesions (LSIL), high-grade squamous intraepithilia lesions (HSIL) and CCC, respectively, showing decreasing levels of positive expression rate ( P<0.05). In the cervical histology group, the positive rate of HPV L1 expression was 86.67%, 65.00%, 34.38%, 11.76% and 4.00% in chronic cervicitis tissues, CIN 1 group, CIN 2 group, CIN 3 group and CC group, respectively, showing decreasing levels of positive expression ( P<0.05). ②In the cervical cytology group, the average positive expression scores of PD-L1 in the cervical inflammatory cells, LSIL group, HSIL group, and CCC group were 0.25±0.12, 1.05±0.67, 1.39±0.11 and 2.14±0.17, respectively, showing increasing levels of positive expression scores ( P<0.05). In the cervical histology group, the average positive expression scores of PD-L1 were 0.28±0.24, 1.21±0.79, 1.56±0.26, 1.80±0.24, and 2.10±0.19 in the chronic cervicitis tissue, CIN 1 group, CIN 2 group, CIN 3 group and CC group, respectively, showing increasing levels of positive expression scores ( P<0.05). The relative expression of PD-L1 mRNA in chronic cervicitis tissue and CC is 1.02±0.04 and 1.81±0.22, respectively ( P<0.05). ③The sensitivity and specificity of diagnosis of cervical tissue CIN2 and abovelesions, HPV L1 detection alone was 95.8%, 47.2%, PD-L1 detection alone was 96.5%, 32.8%, colposcopy alone was 77.5%, 70.8%, HPV L1/PD-L1 tests combined detection was 92.4%, 64.5%, HPV L1/PD-L1 detection combined colposcopy was 71.6% and 89.6%, respectively. The sensitivity and specificity of the HPV L1/PD-L1 combined test for the diagnosis of CIN3 and above cervical lesions were 71.9% and 86.1%, HPV L1/PD-L1 combined with colposcopy were 50.5% and 100.0%, respectively. CONCLUSION: The specificity of HPV L1/PD-L1 detection combined with colposcopy for CIN2 and above lesions is higher than that of HPV L1 detection alone, PD-L1 detection alone and colposcopy alone. HPV L1/PD-L1 detection combined with colposcopy detection for CIN3 and above lesions has an important auxiliary diagnostic value.

Stability Study of Cervical Specimens Collected by Swab and Stored Dry Followed by Human Papillomavirus DNA Detection Using the cobas 4800 Test.

Safer, more convenient methods for cervical sample collection and storage are necessary to facilitate human papillomavirus (HPV) DNA testing in low-resource settings. Our study aimed to evaluate the stability of cervical specimens collected with dry swabs and stored dry, compared to liquid-based cytology (LBC) samples, as detected by HPV DNA testing. Women with abnormal cytological findings or HPV-positive results at colposcopy were recruited from the West China Second University Hospital, Sichuan University, between October 2013 and March 2014. From each woman, physicians collected cervical specimens with a swab placed into a Sarstedt tube and a CytoBrush placed into LBC medium. Samples were randomly assigned to be stored at uncontrolled ambient temperature for 2, 7, 14, or 28 days and then were tested for 14 high-risk HPV (HR-HPV) types using the cobas HPV test. The rates of agreement between dry swab and LBC samples for any HR-HPV type, HPV16, HPV18, and the 12 pooled HR-HPV types were 93.8%, 97.8%, 99.4%, and 93.2%, respectively, with kappa values of 0.87 (95% confidence interval [CI], 0.83 to 0.91), 0.94 (95% CI, 0.91 to 0.97), 0.94 (95% CI, 0.87 to 1.00), and 0.86 (95% CI, 0.82 to 0.90). The performance of swab samples for detection of cervical precancerous lesions by means of cobas HPV testing was equal to that of LBC samples, even with stratification by storage time. Dry storage of swab-collected cervical samples can last for 1 month without loss of test performance by cobas HPV testing, compared to LBC samples, which may offer a simple inexpensive approach for cervical cancer screening in low-resource settings.

p16 Immunohistochemistry Interpretation by Nonpathologists as an Accurate Method for Diagnosing Cervical Precancer and Cancer.

OBJECTIVE: We conducted a pilot study of whether nonpathologists could accurately diagnose cervical precancer in biopsies using only a basic light microscope, evaluating p16 immunohistochemistry (p16 IHC) of biopsies, and video-based training for both. MATERIALS AND METHODS: Using biopsies collected as part of a screening study conducted in rural China, we randomly selected 50 biopsies with a precancerous diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) and 50 biopsies with diagnosis of CIN less severe than CIN2, and stained them for p16 using a commercial IHC kit. Twelve nonpathologists of varying educational backgrounds living in Beijing, China received video training and were assigned one of 4 sets of 25 CIN2+ and 25 CIN less severe than CIN2 for evaluation. A pathologist reviewed all 100 cases. RESULTS: The mean sensitivity and specificity of the p16 IHC staining scored by the nonpathologists were 91.7% and 94.1%, respectively, compared to scoring by the pathologist. The readers and the pathologist agreed on p16 IHC scoring for 42 (84%) of the 50 slides of CIN less severe than CIN2 and 37 (74%) of the 50 CIN2+ slides. The mean sensitivity and specificity for consensus CIN2+ of p16 IHC as scored by the readers were 88% and 87%, respectively, versus an overall sensitivity and specificity by the pathologist of 96% and 92%, respectively. CONCLUSIONS: We demonstrated that nonpathologists can accurately diagnose CIN2+ using p16 IHC alone.

p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: a prospective study in China.

p16(INK4A) is strongly expressed in tissues diagnosed as cervical intraepithelial neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but few prospective studies have evaluated p16(INK4A) as a marker for the risk of low-grade CIN (CIN1) progression. We investigated the prevalence of p16(INK4A) immunostaining by CIN grade and whether overexpression of p16(INK4A) in CIN1 predicts future risk for high-grade CIN in Chinese women. 6,557 Chinese women aged 30-49 years were screened from 2003 to 2005 using cytology and carcinogenic HPV test. Colposcopy was performed on women with any abnormal result. p16(INK4A) Immunostaining was performed on biopsies from all women with CIN1, as well as randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies. Women with CIN1 were followed up without treatment. Colposcopy was performed on all untreated women at a 2-year interval. The prevalence of p16(INK4A) staining was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and cancer biopsies, respectively (p < 0.001). HPV positivity was strongly associated with p16(INK4A) staining [odds ratios (OR) = 12.8; 95% confidence intervals (CI): 5.2-31.6]. p16(INK4A) staining of CIN1 biopsies at baseline was associated with an increased risk of finding high-grade CIN over 2 years of follow-up (OR = 1.43; 95% CI: 0.52-3.91). The two-year cumulative incidence of CIN2+ for p16(INK4A) positive women was higher at 10.71% than for p16(INK4A) negative women at 1.30% (crude RR = 8.25, 95% CI: 1.02-66.62). p16(INK4A) overexpression is strongly associated with grade of CIN and risk of progression to high-grade CIN in women with low-grade lesions.

[Pathological characteristics and prognosis of 664 patients with epithelial ovarian cancer: a retrospective analysis].

OBJECTIVE: To analyze clinicopathologic features and risk factors associated with the recurrence and prognosis of epithelial ovarian cancer (EOC). METHODS: 710 EOC patients treated at the West China University Second Hospital from Jan. 2006 to Jun. 2011 were recruited in this study retrospectively. Univariate and multivariate logistic regression models were constructed to evaluate the risk of factors. Kaplan-Meier and log-rank methods were adopted for survival analyses. RESULTS: The final sample included 664 patients with complete and well-documented data. The participants had a mean age of (49.35 +/- 11.58) yr. and 79.07% (525/664) were older than 40 year-old. CA125 was tested in 550 patients before surgery and 82.55% showed abnormal values. Over half (55.57%) of the patients were classified as serious EOC, which was followed by clear cell EOC (12.35%), endometrioid EOC (10. 09%), mucinous EOC (7.68%), and others (14.31%). Stage I (FIGO) comprised 30. 72% of the cases. The patients were followed up on average of (37.48 +/- 12.51) months and 303 died with a mean survival length of (28.54 +/- 9.56) months. Recurrence was found in 126 patients at a median of (26.10 +/- 5.75) months. For the 361 survived, 81. 72% lived without detectable cancer. All patients received surgical operations, including 483 undergoing retroperitoneal lymphadenectomy. The univariate analysis identified older age, advanced FIGO stage, suboptimal debulking, abnormal CA125 values before surgery, undifferentiated, mixed type and serous pathologic subtypes, poor-differentiation and pathogenesis of tumor as risk factors associated with survival prospect. The multivariate logistic regression models confirmed that poor prognosis was associated with older age, advanced FIGO stage, suboptimal debulking and undifferentiated, mixed type and serous pathologic subtype. CONCLUSION: Older age, advanced FIGO stage, high grade differentiation, suboptimal debulking, lymphnode metastasis, and type II EOC are associated with poor prognosis of EOC patients.

[Expression and clinical signification of IL-10 and IL-17 in endometrial cancer].

OBJECTIVE: To explore the expression of IL-10 and IL-17 in endometrial cancer and their relationships with tumor progression. METHODS: The sera levels of IL-10 and IL-17 were detected by enzyme-linked immune-sorbent assay in 15 benign hysterectomies and 15 endometrial cancers, the expressions of IL-10 and IL-17 in the tissue were measured by immunohistochemistry assay (SABC) with the evaluation of IOD value, clinic-pathological characteristics were retrieved and analyzed. RESULTS: Both sera expression and tissue IOD value of IL-10 were significantly higher in endometrial cancer than those in benign uterine, while no difference was found in IL-17 between the two groups. Sera IL-10 of I B-II stage, G2-G3, with myoinvasion, with vas tumor emboli was higher than that of I A stage, G1, without myoinvasion, and without vas tumor emboli, while no difference was found among tissue types. Sera IL-17 of I B-II stage, with myoinvasion, with vas tumor emboli was lower than that of IA stage, without myoinvasion, and without vas tumor emboli, while no difference was found among tumor grades nor tissue types. CONCLUSION: High expression of IL-10 may participate in the genesis and development of uterine endometrial cancer, while low expression of IL-17 may participate in its development.

Impetigo Herpetiformis during pregnancy: a case report and literature review.

BACKGROUND: Impetigo herpetiformis (IH) is a rare pustular dermatosis that typically occurs in pregnant women with unknown etiology. CASE REPORT: We report an 18-year-old primigravida who presented with IH at nearly 30 weeks' gestation and was the first patient reported in mainland China. The patient's condition deteriorated rapidly in spite of treatment with corticosteroids and antibiotics, so we decided to terminate the pregnancy by induction of labor. After vaginal delivery she developed fever and her skin lesions did not disappear naturally. Fortunately her symptoms were resolved with the treatment of antibiotics and acitretin, and at day 60 postpartum her skin lesions had completely disappeared. CONCLUSION: Although IH is associated with high mortality and morbidity in both fetus and mother, a better prognosis could be achieved with an immediate diagnosis and proper treatment. The etiology of IH needs to be further explored and the process of diagnosis and therapy should be standardized.

Exosomal circNFIX promotes angiogenesis in ovarian cancer via miR-518a-3p/TRIM44 axis.

Ovarian cancer (OC) is a gynecological cancer with high mortality. OC-derived exosomal circRNAs can regulate angiogenesis. This study aims to explore the role and mechanism of exosomal circRNA nuclear factor I X (CircNFIX) derived from OC cells in angiogenesis. Quantitative real-time polymerase chain reaction was employed to evaluate the levels of circNFIX, miR-518a-3p, and tripartite motif protein 44 (TRIM44) in OC and adjacent tissues. Exosomes from the ovarian surface epithelial cell (HOSEpiC) and OC cells (SKOV3 or OVCAR3) were isolated by differential centrifugation. Exosomes were cocultured with the human umbilical vein endothelial cells (HUVECs). The angiogenesis capacity was analyzed by Tube formation assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays were used to determine the cell viability and migration ability. The dual-luciferase report, RNA immunoprecipitation (RIP), and RNA pull-down assays were applied to validate the gene's interaction. CircNFIX and TRIM44 expression were higher and miR-518a-3p was lower in OC tissues than in the adjacent tissues. Upregulated circNFIX and TRIM44 were significantly correlated with the tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage of OC patients. HUVECs treated OC-derived exosomes had higher proliferation, migration, and angiogenesis capacities than the control group. While OC-derived exosomal circNFIX silencing restrained HUVECs' proliferation, migration, and angiogenesis, compared with the OC-derived exosomes group. OC-derived exosomal circNFIX positively regulated TRIM44 expression by targeting miR-518a-3p in HUVECs. OC-derived exosomal circNFIX promoted angiogenesis by regulating the Janus-activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) pathway via miR-518a-3p/TRIM44 axis in HUVECs.

CircNFIX stimulates the proliferation, invasion, and stemness properties of ovarian cancer cells by enhancing SH3RF3 mRNA stability via binding LIN28B.

We aimed to study the regulatory roles and mechanism of circular nuclear factor IX (circNFIX) in cancer growth and stemness properties of ovarian cancer (OC). CircNFIX and SH3RF3 levels in OC tissues and cells were tested by quantitative real-time PCR. RNase R treatment quantified circNFIX RNA stability. Molecular interaction among circNFIX, LIN28B, and SH3RF3 was predicted by bioinformatics software and validated through RNA immunoprecipitation (RIP) assay. The gain- or loss-experiments of circNFIX on capabilities of metastasis and stemness in vitro were assessed using Cell Counting Kit-8, Transwell, western blot, and sphere-formation assays. CircNFIX and SH3RF3 were markedly elevated in OC tissues and OC cells. Knocking down circNFIX repressed the proliferation, migration, invasion, and stemness properties of A2780 and SKOV3 cells. The RIP assay verified the direct binding relationship between LIN28B, circNFIX, and SH3RF3. Additionally, overexpression of circNFIX elevated the SH3RF3 expression, while this effect was reversed by LIN28B silence. Rescue experiments demonstrated that the overexpression of SH3RF3 reversed the knockdown of circNFIX on OC cells' proliferation, metastasis, and stemness properties. CircNFIX improved the mRNA stability and translation of SH3RF3 via recruiting LIN28B, thus promoting the proliferation, invasion, and stemness properties of OC cells in vitro.

Potential clinical value of interleukin-31 and interleukin-33 with their receptors expression as diagnostic and predictive factors in endometrial cancer: a case-control study.

Aims: To evaluate the potential role of interleukin-31 and interleukin-33 in diagnosis and prognosis from endometrial cancer. Methods: Tissue samples and clinical data were collected from 260 patients with endometrial cancer and 150 control patients with benign uterine diseases. Immunohistochemistry and ELISA testing quantified the expressions of interleukin-31 and interleukin-33 and their receptors. After surgery, all patients were followed up for an average of 56.3 months. Surgical effects were evaluated based on the patients' symptoms and signs. A two-sided P value <0.05 was considered significant. Results: IL-31, IL-33 and their receptors were significantly accumulated with the progression of endometrial cancer, in comparison to the controls. Moreover, the expressions were correlated with clinical characteristics, including tumor stage, differentiation, and associated with patients' disease-free survival. Conclusions: Limited data was available between the expressions of IL-31 and IL-33 and the receptors in patients with endometrial cancer. Our study findings suggested that the expressions of IL-31 and IL-33 might become possible biomarkers for the diagnosis and prediction in endometrial cancer.

Transcriptome changes induced by RUNX3 in cervical cancer cells in vitro.

Runt-related transcription factor 3 (RUNX3) is a member of Runt domain family that is known to play key roles in various different types of tumor. It was recently demonstrated that RUNX3 may also be associated with cervical cancer. The aim of the present study was to investigate the potential association between transcriptome changes and RUNX3 expression in cervical cancer. A RUNX3 overexpression model was constructed using cervical cancer cell lines by RUNX3 plasmid transfection. It was demonstrated that the upregulated expression of RUNX3 inhibited proliferation of cervical cancer cell lines, particularly SiHa cells, and was associated with the expression of the IL-6, PTGS2, FOSL1 and TNF genes. In addition, it was revealed that the TNF and FoxO pathways may also be affected by RUNX3. Therefore, the expression of the RUNX3 gene may be involved in the occurrence and progression of cervical cancer.

Performance of HPV Genotyping Combined with p16/Ki-67 in Detection of Cervical Precancer and Cancer Among HPV-Positive Chinese Women.

Women with positive high-risk human papillomavirus (hrHPV) need efficient triage testing to determine colposcopy referrals. Triage strategies of combining p16/Ki-67 with extended HPV genotyping were evaluated in this study. In total, 899 women attending cervical cancer screening program and 858 women referred to colposcopy from five hospitals were recruited. All the participants were tested by HPV assays and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal results. HPV genotypes were divided into four strata (HPV16/18, HPV31/33/58/52, HPV45/59/56/66, and HPV51/39/68/35) according to their risks for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The positive rates of four genotype strata among CIN3+ women were 3.47% (HPV51/39/68/35), 7.73% (HPV45/59/56/66), 14.7% (HPV31/33/58/52), and 78.1% (HPV16/18), respectively (P trend < 0.001). The positive rates of p16/Ki-67 increased with the elevation of HPV risk hierarchical from 65.0% in HPV51/39/68/35-positive women to 88.0% in HPV16/18-positive women (P trend < 0.001). p16/Ki-67 was an effective method for risk stratification of CIN2+ among HPV31/33/58/52- and HPV45/59/56/66-positive women [HPV31/33/58/52: OR for dual stain+ (ORDS+) of 26.7 (16.8-42.4) and OR for dual stain- (ORDS-) of 3.87(1.89-7.91); HPV45/59/56/66: ORDS+ of 10.3(5.05-21.0) and ORDS- of 1.27(0.38-4.26)]. The combination of HPV16/18 genotyping and p16/Ki-67 triage of HPV31/33/58/52/45/59/56/66-positive women resulted in a lower referral rate (40.1% vs. 41.3%; P < 0.001) as compared with triage of 12 other HPV-positive women with p16/Ki-67, although sensitivity and specificity levels for these two strategies were identical. Combining HPV extended genotyping and p16/Ki-67 can be considered as a promising strategy for cervical cancer screening and triage.

Prognostic value of estrogen receptor and progesterone receptor status in young Chinese ovarian carcinoma patients.

OBJECTIVE: The purpose of this study was to investigate the expression patterns and prognostic impact of estrogen receptor (ER), progesterone receptor (PR) and their combinations in young patients with ovarian carcinomas (OC) in China. METHODS: We collected data on 86 patients diagnosed of OC younger than or equal to 40 years of age with a long clinical follow-up. Immunohistochemical staining was performed to assess ER and PR expression in paraffin-embedded ovarian cancers. Samples in which more than 10% of cells showed stained nuclei were interpreted as positive for the particular receptor. Survival rates (Kaplan-Meier method) were compared by the log rank test. A multivariate analysis (Cox proportional hazards) was used to determine the independent effect of each variable on survival. RESULTS: ER were found positive in 64.0% of all cases but most highly expressed in serous types (P=0.047). PR-positive expression accounted for 57.0% of all cases and elevated in early FIGO stages and well-differentiated diseases (P=0.004 and 0.012, respectively). The expression of PR, but not ER, was associated with favorable survival in Kaplan-Meier survival analyses (P<0.001). The ER+PR+ combination, which was associated with low FIGO stages (P=0.012) and low tumor grade (P=0.046), showed a superior course of patients' overall survival compared with all other combinations (5-year survival rate 95.0% vs. 73.4%, log rank P=0.001). PR status (hazard ratio 1.93, P<0.001) together with FIGO stage (hazard ratio 2.19, P<0.001) were proved to be independent prognostic factors by multivariate analysis. CONCLUSIONS: This study indicates that the expression of PR, especially the ER+PR+ phenotype predicts a favorable clinical outcome for young patients of OC.

Association of the ARLTS1 variants with familial ovarian cancer risk in China.

ARLTS1 has been identified in chromosome 13q14 as a tumor suppressor gene of the adenosine diphosphate-ribosylation factor family with pro-apoptotic characteristics. The ARLTS1 mutation Trp149Stop and Cys148Arg have been shown to be associated with familial cancers, but limited information is available regarding the impact of ARLTS1 variants on familial ovarian cancer (OC). The aim of this study was to evaluate the ARLTS1 genetic variants associated with familial OC risk in China. We genotyped 85 OC patients with family ovarian/breast history, 80 sporadic OC patients, and 120 controls from general population by denaturing high-performance liquid chromatography screening analysis followed by direct sequencing of the conspicuous polymerase chain reaction products. ARLTS1 Cys148Arg revealed a significant association with an increased risk of familial OC compared with both sporadic cases and controls in a dose-dependent manner (P = 0.0031 and 0.012, respectively). In the clinical-pathological study, our results support previous data in demonstrating that familial OC was associated with younger age at diagnosis (49.7 years vs 53.3 years; P = 0.014), higher proportion of tumors of advanced stages (81.2% vs 67.5%; P = 0.033), and higher rates of serous adenocarcinomas (76.4% vs 53.8%; P = 0.028) compared with sporadic OC cases. To investigate the association between genetic variants of ARLTS1 and the clinical-pathological characteristics of familial OC, we identified a significantly higher proportion of serous adenocarcinoma (55/67, 82.1%) and higher rates of advanced stage tumors (88.1% vs 55.6%; P = 0.004) in ARLTS1 Cys148Arg carriers. We showed a significantly increased risk of familial OC for ARLTS1 Cys148Arg variant, which indicate that ARLTS1 may play a role in familial OC.

[Expression and purification of GST-HPV16E7 fusion protein].

OBJECTIVE: To construct a recombinant prokaryotic expression vector efficiently expressing HPV16E7 and purify GST-HPV16E7 fusion protein. METHODS: The HPV16E7 gene obtained from a local cervical cancer patient was cloned into vector pGEX-4T-1, to generate the recombinant named as pGEX-4T-1-HPV16E7. The recombinant plasmid was transformed into E. coli BL21. After inducing with IPTG the HPV16E7 fusion protein was analyzed by SDS-PAGE and Western blot. B-PER GST Fusion Protein Purification Kit was appkied to purify GST-HPV16E7 fusion protein. RESULTS: The recombinant plasmid pGEX-4T-1-HPV16E7 was successfully constructed. Highly expressed and purified GST-HPV16E7 fusion protein was obtained. The specificity of fusion protein was verified by SDS-PAGE and Western blot. CONCLUSION: GST-HPV16E7 fusion protein was successfully expressed and purified.

The effect of p16/Ki-67 and p16/mcm2 on the detection of cervical intraepithelial neoplasia: a prospective study from China.

2,067 women who underwent cervical cancer screening were included in this study. p16/Ki-67 and p16/mcm2 were performed on the remaining liquid-based cytology (LBC) samples of 125 HPV-positive women and 114 randomly selected HPV-negative women. Women with HR-HPV infection or cytological abnormalities (≥ASC-US) were referred for colposcopy and biopsy. A third-year follow up visit was performed on all women except for CIN2+. The expression of p16/Ki-67 and p16/mcm2 in the HPV16/18 group and in the other 12 HR-HPV group was significantly higher than that in HPV negative group (P<0.05), with odds ratios (ORs) of 16.27 (95% CI: 4.38-60.47) and 4.52 (95% CI: 2.16-9.45) for p16/Ki-67, and 31.28 (95% CI: 6.33-154.56) and 9.10 (95% CI: 4.52-18.33) for p16/mcm2, respectively. The sensitivities to detect CIN2+ and CIN3 + were 94.1% (95% CI: 73.0-99.0) and 92.9% (95% CI: 68.5-98.7) for p16/Ki-67, and 88.2% (95% CI: 65.7-96.7) and 85.7% (95% CI: 60.1-96.0) for p16/mcm2, respectively. Both the sensitivities of the two biomarkers were significantly higher than that of LBC and HPV16/18 genotyping (P<0.05). The three-year cumulative risks of CIN2+ were 69.0%, 48.4%, 34.8% and 50.0% for p16/Ki-67, p16/mcm, LBC and HPV16/18 genotyping. Women who tested positive on both p16/Ki-67 and p16/mcm2 at baseline had the highest RR value (39.64 [95% CI: 9.78-160.72]) of progressing to CIN2+ when compared to those who were negative for both. To conclude, p16/Ki-67 and p16/mcm2 dual staining can enhance the sensitivity of cytology in a single round of screening, and they can be predictors of high grade cervical lesions in the following years.

Proportion of Uterine Malignant Tumors in Patients with Laparoscopic Myomectomy: A National Multicenter Study in China.

BACKGROUND: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. METHODS: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. RESULTS: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. CONCLUSIONS: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.