Questionnaire survey on the prevention and development of cervical cancer in patients with systemic lupus erythematosus in Japan.

OBJECTIVES: The aim is to evaluate the prevention and development of cervical cancer in systemic lupus erythematosus (SLE) patients in Japan and its background based on a questionnaire survey. METHODS: The questionnaire was handed to 460 adult female SLE patients at 12 medical institutions. The participants were grouped by age, and data related to their human papillomavirus vaccination status, age at first coitus, cervical cancer screening, and diagnosis of cervical cancer were analysed. RESULTS: A total of 320 responses were received. Patients aged 35-54 years included a higher proportion of patients whose age at first coitus was <20 years. This group also showed a higher rate of cervical cancer/dysplasia. Only nine patients had a human papillomavirus vaccination history. Adequate frequency of cervical cancer screening was slightly higher (52.1%) among SLE patients than in the Japanese general population. However, 23% of the patients had never undergone examination, primarily because of a feeling of troublesome. The incidence of cervical cancer was significantly higher among SLE patients. One reason for this may be associated with the use of immunosuppressants, although the difference was not significant. CONCLUSIONS: SLE patients are at a higher risk of cervical cancer and dysplasia. Rheumatologists should proactively recommend vaccination and screening examinations for SLE female patients.

P16INK4A expression might be associated with a favorable prognosis for cervical adenocarcinoma via dysregulation of the RB pathway.

Previous studies have largely failed to clarify the relationship between p16INK4A status and cervical adenocarcinoma prognosis. The current study aimed to examine the clinical and pathological significance of p16INK4A expression in several cervical adenocarcinoma subtypes. Eighty-two samples collected from patients with cervical adenocarcinoma were formalin fixed and paraffin embedded. Next, p16INK4A levels were analyzed with immunohistochemistry. Additionally, the relationship between p16INK4A expression and clinicopathological factors as well as prognosis was evaluated. The expression of p16INK4A was mostly detected in all usual cervical adenocarcinoma subtypes. In the gastric type, only a few cases were positive for p16INK4A expression. Results of the Kaplan-Meier analysis indicated that the positive p16INK4A expression in tumor cells was significantly associated with favorable progression-free survival and overall survival in patients with cervical adenocarcinoma (p = 0.018 and p = 0.047, respectively, log-rank test). Our findings suggest that the status of p16INK4A expression may influence prognosis. Thus, p16INK4A expression could be used as a biomarker for improving the prognosis of patients with cervical adenocarcinoma.

Damus-Kay-Stansel procedure with ventricular septal defect enlargement.

A full-term infant who had tricuspid atresia with transposed great arteries, a ventricular septal defect, subpulmonary stenosis with posterior malalignment of the conus septum, bicuspid pulmonary valve, and a high-takeoff left coronary artery was referred to our institution. The subpulmonary stenosis gradually progressed and cyanosis worsened. We successfully performed a Damus-Kay-Stansel procedure and a bidirectional Glenn shunt concomitant with ventricular septal defect enlargement. The conus septum was resected along with thick fibrous tissue through both semilunar valves (without ventriculotomy). Postoperative echocardiography demonstrated that both the ventricular septal defect and the subpulmonary space were enlarged effectively without semilunar valve regurgitation.

Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates.

Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.

Pathological findings in the endometrium after microwave endometrial ablation.

The acceptance of MEA in Japan is well demand due to its outstanding effectiveness and safety. Infrequently, a repeat MEA or hysterectomy is needed for recurrent menorrhagia in case of failure ablation. The reasons of recurrent menorrhagia subsequent MEA treatment are unclear. The objective of current study is to identify the possible causes of menorrhagia repetition following MEA, together with the observation of histological changes in the endometrium due to this treatment compared with normal cycling endometrial tissue. A total of 170 patients, 8 (4.7%) of them carried out hysterectomy after 16.8 months (range, 2-29 months) of MEA treatment. Normal (n = 47) and MEA (n = 8) treated paraffin embedded endometrial tissue were prepared for hematoxylin and eosin (H&E) and immunostaining study to recognize the histological changes in the endometrium as a result of MEA treatment. The histological features observed increased tubal metaplasia (TM) including negative expression of the estrogen receptor (ER) and progesterone receptor (PR) in the endometrium subsequent MEA treatment. Increased TM together with the absence of ER and PR expression might be a reasonable explanation for repetition menorrhagia in cases of failure ablation. Further study is required to clarify the molecular mechanisms of tubal metaplasia and the expression loss of hormone receptor in the endometrium as a result of MEA treatment. Current studies propose that low dose estrogen-progestin may not be effective with recurrent menorrhagia patient's due to the inadequacy of hormone receptor expression in the endometrium following MEA.

Mucinous borderline ovarian tumors with BRAFV600E mutation may have low risk for progression to invasive carcinomas.

PURPOSE: Mucinous ovarian carcinomas (MOCs) are relatively rare. It has been proposed that a subset of mucinous cystadenomas (MCAs) may progress to mucinous borderline tumors (MBTs), and then to MOCs. KRAS is the predominantly mutated gene in MOC; however, other associated mutations and the mechanism underlying carcinogenesis in MOC remain unclear. Here, we assessed molecular genetic alterations in mucinous ovarian tumors and constructed mutation profiles. METHODS: Using the Sanger sequencing method, we assessed genetic mutations (KRAS, BRAF, TP53, and PIK3CA) in 16 cases of MOC, 10 cases of MBT, and 12 cases of MCA. RESULTS: Among MOC cases, the prevalence of G12D and G13D KRAS mutations was 43.8% (7/16). No MOC cases showed V600E BRAF and TP53 mutations. Among MBT cases, the prevalence of G12D KRAS mutation was 20.0% (2/10), those of TP53 and PIK3CA mutations were nil, and that of V600E BRAF mutation was 40% (4/10). None of the genetic mutations assessed were detected among MCA cases. CONCLUSION: These results suggest that MBT with V600E BRAF mutation may rarely progress to MOC, while MBT with G12D or G13D KRAS mutation may more commonly progress to MOC.

High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.

PURPOSE: The effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. Programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 may be used as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of patients with CA and their response to immune checkpoint inhibition therapy. METHODS: In the present study, the clinical stage for all 82 patients with cervical adenocarcinoma was classified according to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO); there were 5, 48, 5, 14, 8, and 2 patients with stage IA, IB, IIA, IIB, IIIB, and IVB disease, respectively. The levels of PD-1, PD-L1, and CD8 were analyzed by the immunohistochemical analysis of the formalin-fixed paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed using the Kaplan-Meier method and univariate and multivariate Cox proportional hazard regression models. RESULTS: We observed a significant inverse correlation between the expression of PD-1 and CD8 (p = 0.001, chi-square test). We also found a significant inverse correlation between the expression of PD-L1 and CD8 (p = 0.027). The overall survival and progression-free survival rates were significantly worse in patients with positive PD-1 expression (p = 0.031; p = 0.087, respectively). CONCLUSION: Our results suggest that a high PD-1 expression is associated with a poor prognosis in patients with CA. Further research is necessary to identify the molecular mechanisms that mediate this association.

Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future.

Ovarian cancer has the worst prognosis among gynecological cancers. Thus, new ovarian cancer treatment strategies are needed. Currently, immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibody are attracting attention worldwide. The Food and Drug Administration approved the use of the PD-1 antibody pembrolizumab for solid cancers with microsatellite instability (MSI)-H or mismatch repair (MMR) deficiency in 2017. However, few studies on ovarian carcinoma have evaluated the relationship among MSI status, lymphocyte infiltration into the tumor, and the expression of immune checkpoint molecules by histologic type. We evaluated the expression of MMR proteins, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunohistochemistry in 136 ovarian cancer patients (76, 13, 23, and 24 cases were high-grade serous, mucinous, endometrioid, and clear cell carcinoma, respectively) to investigate the effectiveness of immune checkpoint inhibitors. Only six cases (4.4%) had loss of MMR protein expression. There was no significant relationship between MSI status and age (p = 0.496), FIGO stage (p = 0.357), initial treatment (primary debulking surgery [PDS] or neoadjuvant chemotherapy) (p = 0.419), residual tumor after PDS or interval debulking surgery (p = 0.202), and expression of CD8 (p = 0.126), PD-L1 (p = 0.432), and PD-1 (p = 0.653). These results suggest that only a small number of MSI cases in ovarian cancer can be effectively treated with immune checkpoint inhibitor monotherapy. Therefore, to improve the prognosis of ovarian carcinoma, a combination therapy of immune checkpoint inhibitors and other anticancer drugs is necessary.

Fatal Postpartum Hemorrhage in Diffuse Midline Glioma with H3-K27M Mutation.

Management of pregnant women with brain tumors necessitates difficult decision-making especially for estimating or preventing its intratumoral hemorrhage. A 26-year-old, 19-week pregnant woman complaining of headache and vomiting was admitted to our hospital. Magnetic resonance imaging (MRI) revealed hydrocephalus and a mass lesion without contrast enhancement extending from the left thalamus. To resolve severe symptoms, a ventriculoperitoneal shunt was inserted, and a biopsy was taken via the right ventricle. Pathological examination suggested diffuse or pilocytic astrocytoma, but subsequent genetic analysis revealed the diagnosis of midline glioma with H3-K27M mutation. The patient opted not to terminate the pregnancy, and MRIs conducted every four weeks revealed no change in tumor aspect. The patient delivered a healthy baby by cesarean section, and postpartum day 1 was uneventful. However, she was found in a coma due to a massive intratumoral hemorrhage on postpartum day 2 and died 3 weeks after the hemorrhage. This is the first case report of diffuse midline glioma with H3-K27M mutation in a pregnant woman followed by fatal hemorrhage. It highlights the necessity of careful clinical management and frequent neuroimaging during the entire perinatal period, even if the tumor has hypovascularity or low proliferative potential on radiological or pathological findings.

Clinicopathological and biological analysis of PIK3CA mutation and amplification in cervical carcinomas.

The aim of the present study was to evaluate the mutation and amplification status of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) gene, as well as the association with clinicopathological characteristics and prognosis, in Japanese patients with cervical cancer. Fluorescence in situ hybridization and polymerase chain reaction were performed to assess PIK3CA gene amplification and mutation. The inhibitors temsirolimus and NVP-BEZ235 were used to inactivate the phosphatidylinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin kinase (mTOR) pathway to clarify the roles of PI3K/AKT activation in cervical carcinoma cells harboring associated mutations. Four somatic point mutations (4/71, 5.6%) were found in exon 20 in cervical squamous cell carcinoma samples, whereas three (3/53, 5.7%) were found in exon 9 in cervical adeno/adenosquamous cell carcinoma samples. Amplification of PIK3CA was also observed in this study and amplification was more commonly found in adeno/adenosquamous carcinomas than in cervical squamous cell carcinomas (20.7 vs. 1.4%, respectively, P=0.0003). No significant correlation was obesrved between PIK3CA amplification and progression free survival (P=0.7576) or overall survival (P=0.8859). Moreover, no association between PIK3CA mutation and sensitivity to PI3K/AKT/mTOR inhibitors was observed in cervical carcinoma cells. These results suggest that in Japanese patients with cervical cancer, PIK3CA mutation and amplification cannot act as biomarkers for individualized molecular targeted therapy.

Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).

Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.

High frequency of POLE mutations in synchronous endometrial and ovarian carcinoma.

Synchronous endometrial and ovarian carcinomas) represent 5% to 10% of endometrial or ovarian carcinomas. We assessed genetic alterations (in PTEN, CTNNB1, POLE, etc) and evaluated correlations with patient outcomes to determine the utility of clonality analyses for differentiating between metastases and concurrent primary tumors and for determining whether genetic alterations in synchronous tumors are predictive of biological behavior. Genomic DNA was isolated from formalin-fixed, paraffin-embedded tissues and frozen tissues from patients with synchronous endometrial and ovarian carcinomas. Samples were obtained from the Department of Obstetrics and Gynecology at the Shimane University School of Medicine between 2003 and 2017. Sanger sequencing was used to analyze the mutational status of the coding exons in TP53, PTEN, POLE, PIK3CA, KRAS, and CTNNB1 using previously published primers. All patients lived, and 3 had disease recurrence. The frequencies of somatic mutations in TP53, PTEN, CTNNB1, KRAS, and POLE were 3 (37.5%), 2 (25.0%), 3 (37.5%), 0 (0.0%), and 5 (62.5%) of 8 cases in ovarian tumors and 3 (37.5%), 2 (25.0%), 3 (37.5%), 1 (12.5%), and 5 (62.5%) of 8 cases in endometrial tumors, respectively. The frequencies of POLE and CTNNB1 mutations were higher than those in previous reports. A clonal relationship was determined by genomic analyses in 3 of 6 cases that were initially diagnosed as primary independent tumors. We confirmed that these 3 cases were indicated metastatic tumors because the lesion of mutation was the same. This information, provided by the sequencing-based strategy, could be useful for hypothesizing a patient's prognosis and deciding on treatment.

Prognostic significance of pre-treatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in non-surgically treated uterine cervical carcinoma.

The aim of the present study was to assess the prognostic significance of the pre-treatment neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and other clinicopathological characteristics in patients with non-surgically treated uterine cervical carcinoma. The correlations of clinicopathological characteristics with overall and progression-free survival were determined in 98 Japanese patients who received non-surgical treatment for uterine cervical carcinoma between January 1997 and July 2013. Survival rates were calculated using the Kaplan-Meier method and potential prognostic indicators were assessed using a Cox proportional hazards model. A total of 68 patients (69.4%) had a high pre-treatment NLR (≥3.5) and 34 patients (34.7%) had a high pre-treatment PLR (≥212). Both NLR and PLR were found to be positively correlated with pre-treatment platelet counts. Multivariate analysis identified NLR and carcinoembryonic antigen level, but not PLR, as independent predictors of overall and progression-free survival. In conclusion, the present study identified two prognostic indicators for uterine cervical carcinoma, both of which can be easily and cost-effectively monitored via blood testing.

Ultrasound-guided intranodal lymphangiography with lipiodol for treatment of chylous ascites following surgery for ovarian cancer: A case report.

Although lymphadenectomy for gynecological cancer is often associated with chylous leakage, the proper management of this complication remains a matter of debate. In the present study a case of chylous leakage successfully treated with lipiodol lymphangiography is described. A 33-year-old patient with ovarian cancer experienced chylous leakage following total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. The volume of fluid in the abdominal drainage tube increased to 800-1,000 ml/day on postoperative day (POD)3. The patient was started on a fat-restricted diet on POD3 and octreotide on POD21, but the volume of the discharge remained unchanged. Lipiodol lymphangiography was performed on POD62, which reduced the leakage, and the patient was discharged on POD95. Therefore, lipiodol lymphangiography effectively resolved chylous leakage following surgery for gynecological cancer. The aim of the present study was to report the clinical effectiveness of lipiodol lymphangiography in resolving chylous leakage in such cases, and to summarize the methods used and complications encountered.

ARID1B as a Potential Therapeutic Target for ARID1A-Mutant Ovarian Clear Cell Carcinoma.

AT-rich interactive domain 1A (ARID1A) and AT-rich interactive domain 1B (ARID1B) are subunits of the SWI/SNF chromatin complex. ARID1A is a tumor suppressor gene that is frequently mutated (46%) in ovarian clear cell carcinomas (OCCC). Loss of ARID1B in an ARID1A-deficient background eliminates the intact SWI/SNF complex, indicating that ARID1B is essential for the formation or stabilization of an intact SWI/SNF complex and, thus, the survival of ARID1A-mutant cancer cell lines. In this study, we investigated the clinicopathologic and prognostic relevance of ARID1B in OCCC by immunohistochemical analysis of 53 OCCC patient samples and loss-of-function experiments in OCCC cell lines. We also examined whether ARID1B could be a therapeutic target or prognostic biomarker in OCCC. siRNA-mediated knockdown of ARID1B in an ARID1A-mutant cell line significantly decreased cell growth, whereas concurrent depletion of both ARID1A and ARID1B was required to decrease wild type cell growth. In the immunohistochemical analyses, low ARID1B level was frequent in samples lacking ARID1A and was associated with shorter progression-free survival. This is the first report demonstrating that a low ARID1B level could be a marker of poor prognosis in OCCC. Moreover, the correlation between the loss of ARID1A immunoreactivity and reduced ARID1B levels indicates that ARID1B could be an attractive target for anti-cancer therapy.

Genetic analysis and phosphoinositide 3-kinase/protein kinase B signaling pathway status in ovarian endometrioid borderline tumor samples.

Ovarian endometrioid borderline tumors (EBTs) are extremely rare, and are thought to be precursors of endometrioid carcinoma, beginning as adenofibroma or endometriosis and progressing in a slow, stepwise manner. In endometrioid carcinomas, a high frequency of activating mutations in phosphatase and tensin homolog (PTEN), ß-catenin or AT-rich interaction domain 1A (ARID1A) genes, and the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway have been observed. However, the frequency of these alterations in EBTs and how they contribute to tumor progression remain unclear. To the best of our knowledge, this is the first study to assess the status of the PI3K/AKT signaling pathway in EBTs, in association with PTEN and ARID1A mutations. PTEN mutations were observed in EBTs and also in the area of endometriosis without atypia. However, the PI3K/AKT signaling pathway was revealed to be activated only in EBTs. The observations of the present study suggest that the PTEN mutation represents an early event in EBT tumorigenesis, while additional genetic alterations may be necessary to activate the PI3K/AKT signaling pathway and induce the development of the invasive carcinoma.

Preoperative tumor size is associated with deep myometrial invasion and lymph node metastases and is a negative prognostic indicator for patients with endometrial carcinoma.

We examined the usefulness of evaluating tumor size determined using preoperative magnetic resonance imaging (MRI) for prognosis in patients with endometrial carcinoma (EC). Patients (N = 184) with EC who underwent surgery at Shimane University Hospital between 1997 and 2013 were enrolled. We investigated the association between the tumor size of EC assessed prior to surgery by MRI (anteroposterior [AP], transverse [TV], and craniocaudal [CC] diameters) and various clinical parameters including deep myometrial invasion and lymph node metastases. We subsequently examined the prognostic significance of tumor size in patients with EC. Survival analysis was performed using the Kaplan-Meier method, and prognostic factors were evaluated using the Cox's proportional hazards regression model. Multivariate analysis identified increased AP diameter as an independent negative prognostic factor for overall survival (OS) (P = 0.037). A long AP diameter has prognostic value and the potential to be a predictive marker for surgical outcomes in patients with EC. Furthermore, AP diameter exhibited the greatest area under the curve (AUC) (0.727) for deep myometrial invasion, and CC diameter had the greatest AUC for lymph node metastases (0.854). Evaluation of tumor size parameters may aid in the identification of high-risk populations, which could improve treatment selection and patient outcomes.

Affinity-purified DNA-based mutation profiles of endometriosis-related ovarian neoplasms in Japanese patients.

AIM: Endometriosis-related ovarian neoplasms (ERONs) have recently attracted considerable attention; however, the prevalence and patterns of ARID1A and POLE mutations in ERONs have not been studied in detail. The aim of this study was to investigate not only the carcinogenesis of ERONs, but also the prognostic significance of several gene mutations in this cohort. We used DNA purified from only tumor epithelial cells, from which fibroblasts were removed, using a specific method we called "liquid microdissection". METHODS: Tissue samples from 22 ovarian carcinomas (13 endometrioid, and nine clear cell) were used. Tumor cells were isolated using a cell sorting system and DNA was purified from tumor epithelial cells. Nucleotide sequencing was conducted to analyze the mutational status of ARID1A, p53, PTEN, POLE, PIK3CA, and KRAS. RESULTS: In ERONs, the frequencies of somatic mutations in ARID1A, p53, POLE, PTEN, PIK3CA, and KRAS were 19/20 (95.0%), 7/19 (36.8%), 9/22 (40.9%), 13/19 (68.4%), 3/19 (15.8%), and 1/9 (11.1%). The frequency of ARID1A mutations was significantly higher than that reported previously. Kaplan-Meier survival analysis revealed that mutations in all genes, including POLE, were not associated with patient prognosis in our Japanese cohort. CONCLUSIONS: Our results suggest that the frequency of ARID1A mutations in ERONs may be higher than that previously reported. In addition, the "liquid microdissection" method that we chose for DNA purification could be used to obtain high-quality sequencing results. The findings suggest that ARID1A mutations represent the basis of ERON carcinogenesis; other subsequent gene mutations may result in the progression of carcinogenesis.

Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report.

Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), MutS Homolog 6 (MSH6), and PMS1 Homolog 2 (PMS2)). The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related clear cell carcinoma of the cervix, which indicates the possibility of an association between cervical cancer and Lynch syndrome. Suitable genetic tests are required to determine whether common genetics can account for synchronous or subsequent malignancies in Lynch syndrome patients and their families. Such knowledge will also enhance our understanding of the genetic mechanisms governing the development of apparently unrelated cancers.

Loss of beclin 1 expression in ovarian cancer: A potential biomarker for predicting unfavorable outcomes.

The clinicopathological significance and prognostic value of the expression of proteins associated with autophagy, beclin 1 (BECN1), 1A/1B-light chain 3 (LC3) and high mobility group box-1 protein (HMGB-1), were investigated in patients with ovarian carcinoma, receiving combination chemotherapy with a platinum agent and a taxane. Immunohistochemical staining was performed for autophagy-associated proteins in tumor tissues from 141 patients with ovarian carcinoma. Clinical data were collected retrospectively by reviewing medical charts, and the association between protein expression, clinicopathological features and survival was investigated. Amongst 141 ovarian carcinoma samples, the loss of BECN1, LC3, and HMGB-1 expression was identified in 59 (41.8%), 35 (24.8%), and 66 (46.8%) samples, respectively. Clinicopathological factors were not significantly associated with the loss of BECN1 expression. However, significant associations were demonstrated between the expression of BECN1, LC3, and HMGB-1. In addition, loss of BECN1 expression demonstrated a significant association with poor progression-free and poor overall survival. Multivariate analysis demonstrated that loss of BECN1 expression and postoperative residual tumor were significant independent predictors of poor progression-free survival and poor overall survival. These results indicated that loss of BECN1 expression in ovarian carcinoma is a negative prognosticator in patients receiving platinum-based chemotherapy. Assessment of BECN1 expression may be useful for predicting an unfavorable response to platinum-based chemotherapy in ovarian carcinoma.