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.

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.

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.

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.

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.

KRAS/BRAF Analysis in Ovarian Low-Grade Serous Carcinoma Having Synchronous All Pathological Precursor Regions.

Ovarian low-grade serous carcinoma is thought to begin as a serous cystadenoma or adenofibroma that progresses in a slow stepwise fashion. Among the low-grade serous carcinomas, there is a high frequency of activating mutations in the KRAS or BRAF genes; however, it remains unclear as to how these mutations contribute to tumor progression. This is the first report to track the histopathological progression of serous adenofibroma to low-grade serous carcinoma. Each stage was individually analyzed by pathological and molecular genetic methods to determine what differences occur between the distinct stages of progression.

Characteristic expression of p57/Kip2 in balloon cells in focal cortical dysplasia.

Balloon cells are a pathognomonic cellular feature of various cortical malformations, including focal cortical dysplasia type IIb (FCD IIb), cortical tubers of tuberous sclerosis (TSC) and hemimegalencephaly (HME). In the present study, we investigated the immunohistochemical expression of p57/Kip2, a member of the Cip/Kip family of cyclin-dependent kinase inhibitory proteins, in balloon cells in surgical specimens taken from 26, 17 and six patients with FCD IIb, TSC and HME, respectively. Characteristic dot-like reactivity with a faint, intense, reticular and process-like pattern was confined to the proximal portion of the cytoplasmic processes of the cells. Immunoelectron microscopy revealed the p57/Kip2 reactivity on intermediate filaments in the proximal portion of the processes. The immunohistochemical profile appeared similar to that of CD34; however, a double immunofluorescence study demonstrated that no cells showed reactivity for both p57/Kip2 and CD34. The frequencies of the p57/Kip2-positive cells in FCD IIb and HME were significantly higher than those in TSC, suggesting that the balloon cells may be heterogeneous. These findings suggest some functional significance of the protein on the cytoplasmic processes of balloon cells and appear consistent with the notion that the cells are abnormally differentiated progenitor cells.

Microwave endometrial ablation at a frequency of 2.45 GHz for menorrhagia: analysis of treatment results at a single facility.

AIM: We aimed to evaluate the efficacy of microwave endometrial ablation at a frequency of 2.45 GHz in women with menorrhagia. This method has been attracting attention as an alternative to hysterectomy in the treatment of functional and organic menorrhagia. MATERIAL AND METHODS: We performed microwave endometrial ablation in 103 women with menorrhagia between August 2007 and October 2012. All patients had completed child bearing. We evaluated the efficacy of microwave endometrial ablation using a visual analog scale for menorrhagia, dysmenorrhea, and patient satisfaction. We also evaluated the incidence of hypermenorrhea recurrence, amenorrhea, and procedure complications in relation to patients' clinical factors, such as the presence of myoma, adenomyosis, uterine size, and type of bleeding. RESULTS: A total of 76 patients completed the evaluation period. Excessive menstruation improved from a preoperative mean visual analog score of 10, to 1.9 after treatment. Dysmenorrhea improved from a mean score of 4.2, to 1.3, and patient satisfaction had a mean score of 9.0. Hemoglobin levels improved from 10.1 g/dL preoperatively to 12.5 g/dL postoperatively. Four patients experienced recurrence of excessive menstruation. No related clinical factors could be identified for recurrence risk or the occurrence of postoperative infection. A total of 26 patients (34.2%) became amenorrheic; these patients were less likely to have myomata, intramural myomata, and myomata larger than 5 cm. CONCLUSIONS: Microwave endometrial ablation at a frequency of 2.45 GHz is an effective and safe treatment. It should be considered as a standard treatment for conservative therapy-resistant menorrhagia.

[Epilepsy surgery in children with tuberous sclerosis complex].

Tuberous sclerosis complex (TSC) has been known to present a high incidence (60-90%) of epilepsy due to cortical tubers. In 50 to 80% of the epilepsy patients with TSC, epileptic seizures become resistant against anti-epileptic medications. The multiple cortical tubers are considered to promote the wide epileptic network in a part of TSC patients. The extensive and disrupted epileptic network with the multiple tubers and abnormal cortices are highly correlated with their complicated epileptogenesis. In a subset of TSC patients, the distribution of epileptogenic zone can propagate from a single focus at the beginning of seizure history, to bilateral and multiple foci during the clinical course. We found that the laterality of spikes during rapid-eye-movement (REM) sleep despite of diffuse and multifocal spikes during non-REM sleep on the long-term video EEG monitoring related with the laterality of the epileptogenic hemisphere. Furthermore, the pattern of distribution of equivalent current dipoles on magnetoencephalography (MEG) can be applied to identify epileptogenic zone among multiple cortical tubers. This paper presents roles of pediatric neurologists to which patients are candidate for surgical treatments and when is the best to offer surgery; using the long-term video EEG and MEG.

Evaluation of ARID1A as a Potential Biomarker for Predicting Response to Immune Checkpoint Inhibitors in Patients with Endometrial Cancer.

BACKGROUND: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment. METHODS: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis. RESULTS: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage. CONCLUSION: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer.

Fatty acid synthase is a potential therapeutic target in estrogen receptor-/progesterone receptor-positive endometrioid endometrial cancer.

OBJECTIVE: In the current study we investigated the clinicopathological significance of fatty acid synthase (FASN) expression and its relationship with estrogen receptor (ER) and progesterone receptor (PR) in endometrioid endometrial cancer. METHODS: FASN expression in endometrioid endometrial cancer was assessed by immunohistochemistry using 108 paraffin-embedded tissue specimens and clinical data collected from a retrospective chart review. The specific FASN inhibitor C75 was used to analyze the relationship between FASN expression and cell growth as well as ER/PR expression in endometrioid endometrial cancer cell lines. RESULTS: Positive FASN immunostaining was observed in 77.8% (84/108) of the tumors analyzed. Deep myometrial invasion was significantly and inversely correlated with positive FASN expression (p = 0.024). Positive ER (p = 0.018) and PR status (p = 0.012) was significantly correlated with positive FASN expression. Patients with positive FASN expression in endometrioid endometrial cancer tissues tended to have a favorable progression-free/overall survival (p = 0.127 and p = 0.087, respectively). Ishikawa cells with high FASN expression also showed high expression of ER/PR, while HEC1B cells had low expression levels of both FASN and ER/PR. FASN inhibition by C75 (10 µM) significantly reduced ER/PR expression compared with control dimethyl sulfoxide treatment of Ishikawa cells. The growth of Ishikawa cells having positive FASN and ER/PR expression was significantly inhibited in the presence of C75 or FASN small-interfering RNA compared to HEC1B cells that lacked FASN and ER/PR expression. CONCLUSION: The current findings suggest that there may be cross talk between the ER/PR and FASN signaling pathways that modulate ER/PR activation and could play a role in endometrioid endometrial cancer pathogenesis.

Is ATP7B a predictive marker in patients with ovarian carcinoma treated with platinum-taxane combination chemotherapy?

OBJECTIVE: This study examined the prognostic significance of copper-transporting P-type adenosine triphosphatase (ATP7B) expression in patients with ovarian carcinoma treated with platinum-taxane combination chemotherapy. METHODS: Expression of ATP7B in ovarian carcinoma was assessed by immunohistochemistry and clinical data collected by retrospective review of medical charts. RESULTS: Overexpression of ATP7B was identified in 25 (29.1%) of 86 ovarian carcinomas. The frequency of ATP7B expression in clear cell carcinomas was significantly higher than that in serous high-grade carcinomas (P < 0.05). We observed no statistically significant correlations between high ATP7B protein expression and either disease-free survival (P = 0.722) or overall survival (P = 0.389). CONCLUSIONS: Our study is the first to demonstrate a lack of statistically significant differences between ATP7B positive and negative cases with respect to prognosis of patients with ovarian carcinoma treated with a platinum-taxane combination regimen. However, that ATP7B expression in clear cell carcinomas was significantly higher than that in serous carcinomas may partially explain the difference in chemotherapeutic response and prognosis between patients with these 2 types of carcinomas.

A Case of Stage III c Ovarian Clear Cell Carcinoma: The Role for Predictive Biomarkers and Targeted Therapies.

Ovarian cancer treatment presently does not reflect molecular differences in histologic subtype. Ovarian clear cell carcinoma (OCCC) exhibits several differences in terms of molecular pathogenesis and tumor behavior from the more common, chemosensitive, serous carcinomas, which makes OCCC a candidate for targeted therapies. A 53-year-old Japanese woman was diagnosed with stage IIIc ovarian clear cell adenocarcinoma with marked chemoresistance to conventional regimens. She demonstrated a partial response to a multikinase inhibitor. The tumor was resistant to PI3K/mTOR pathway inhibitors despite harboring a PIK3CA mutation. The present case suggests a role for targeted therapies in the treatment of OCCC and a need for the identification of biomarkers that will predict response to targeted therapies.

KRAS and MAPK1 gene amplification in type II ovarian carcinomas.

In this study, we examined the clinical significance of KRAS and MAPK1 amplification and assessed whether these amplified genes were potential therapeutic targets in type II ovarian carcinoma. Using fluorescence in situ hybridization, immunohistochemistry, and retrospectively collected clinical data, KRAS and MAPK1 amplifications were identified in 9 (13.2%) and 5 (7.4%) of 68 type II ovarian carcinoma tissue samples, respectively. Interestingly, co-amplification of KRAS and MAPK1 seemed to be absent in the type II ovarian carcinomas tested, except one case. Active phospho-ERK1/2 was identified in 26 (38.2%) out of 68 type II ovarian carcinomas and did not correlate with KRAS or MAPK1 amplification. There was no significant relationship between KRAS amplification and overall or progression-free survival in patients with type II ovarian carcinoma. However, patients with MAPK1 amplification had significantly poorer progression-free survival than patients without MAPK1 amplification. Moreover, type II ovarian carcinoma cells with concomitant KRAS amplification and mutation exhibited dramatic growth reduction following treatment with the MEK inhibitor PD0325901. These findings indicate that KRAS/MAPK1 amplification is critical for the growth of a subset of type II ovarian carcinomas. Additionally, RAS/RAF/MEK/ERK pathway-targeted therapy may benefit selected patients with type II ovarian carcinoma harboring KRAS/MAPK1 amplifications.

Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma.

BACKGROUND: The goal of this study was to examine the clinical significance of ZNF217 amplification and assess whether ZNF217 could be a potential therapeutic target in ovarian clear cell carcinoma (OCCC). METHODS: ZNF217 expression and amplification in OCCC was assessed by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected via a retrospective chart review. ZNF217 gene knockdown using silencing RNA (siRNA) was used to assess ZNF217 functions in OCCC cell lines. RESULTS: Gene amplification was identified in 12 of 60 (20.0%) OCCCs. ZNF217 copy number correlated significantly with ZNF217 protein expression (r = 0.341; P<.01). ZNF217 amplification correlated significantly with shorter progression-free (P = .0042) and overall (P = .0199) survival. There were nonsignificant trends between high ZNF217 protein expression and poor progression-free (P = .2594) and overall (P = .2199) survival. Multivariate analysis revealed ZNF217 gene amplification to be an independent prognostic factor for progression-free and overall survival after standard platinum agent-based chemotherapy (P = .0339 and P = .031, respectively). Profound growth inhibition and apoptosis were observed in ZNF217 siRNA-treated cancer cells with gene amplification compared with cancer cells with ZNF217 moderate expression without ZNF217 gene amplification or with low ZNF217 expression. CONCLUSION: These findings indicate that ZNF217 overexpression is critical to growth and survival of OCCCs with ZNF217 gene amplification. Furthermore, they suggest that ZNF217 siRNA-induced phenotypes depend on amplification status of OCCCs. Therefore, ZNF217-targeted therapy may benefit OCCC patients with ZNF217 amplification.

Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma.

Recently, the ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma. The prognostic significance of the loss of ARID1A expression is not known. The current study was designed to evaluate whether ARID1A was a prognostic factor for progression, survival, and chemoresistance in ovarian clear cell carcinoma. A total of 60 patients, who were surgically treated for primary ovarian clear cell adenocarcinoma, were enrolled. Surgical specimens were examined for ARID1A protein expression by immunohistochemistry. The correlations between the loss of ARID1A expression and clinicopathological characteristics, prognosis, and chemosensitivity were investigated. Loss of ARID1A expression was identified in 9 (15.0%) of 60 ovarian clear cell carcinoma samples. Loss of ARID1A staining intensity (0+) was more frequently found in cells of clear cell carcinomas than in high-grade serous carcinomas (P<0.01). Loss of ARID1A expression was significantly correlated with advanced FIGO stage and high CA125 levels (P=0.02, 0.01). There were no significant correlations between loss of ARID1A expression and patient age, status of residual tumor, Ki-67 labeling index, or the status of endometriosis. Loss of ARID1A correlated with shorter progression-free survival of patients with clear cell carcinomas treated with platinum-based chemotherapy (P<0.01). Loss of ARID1A expression tended to correlate with shorter overall survival in patients with ovarian clear cell carcinomas treated with platinum-based chemotherapy. When data were stratified for the multivariate analysis, only the loss of ARID1A expression remained a significant (P=0.03) predictor of reduced progression-free survival. Of the 60 patients with ovarian clear cell carcinomas, 14 patients had measurable residual tumor after primary cytoreductive surgery. Tumors with loss of ARID1A expression were more likely to be chemoresistant than tumors with positive ARID1A expression (100.0 vs 40.0%, P=0.04). This study demonstrates that loss of ARID1A in ovarian clear cell carcinoma is a negative prognostic factor in patients treated with platinum-based chemotherapy. Measurement of ARID1A expression may be a method to predict resistance to platinum-based chemotherapy in patients with ovarian clear cell carcinoma.

Photocurrent and electronic activities of oriented-His-tagged photosynthetic light-harvesting/reaction center core complexes assembled onto a gold electrode.

A polyhistidine (His) tag was fused to the C- or N-terminus of the light-harvesting (LH1)-α chain of the photosynthetic antenna core complex (LH1-RC) from Rhodobacter sphaeroides to allow immobilization of the complex on a solid substrate with defined orientation. His-tagged LH1-RCs were adsorbed onto a gold electrode modified with Ni-NTA. The LH1-RC with the C-terminal His-tag (C-His LH1-RC) on the modified electrode produced a photovoltaic response upon illumination. Electron transfer is unidirectional within the RC and starts when the bacteriochlorophyll a dimer in the RC is activated by light absorbed by LH1. The LH1-RC with the N-terminal His-tag (N-His LH1-RC) produced very little or no photocurrent upon illumination at any wavelength. The conductivity of the His-tagged LH1-RC was measured with point-contact current imaging atomic force microscopy, indicating that 60% of the C-His LH1-RC are correctly oriented (N-His 63%). The oriented C-His LH1-RC or N-His LH1-RC showed semiconductive behavior, that is, had the opposite orientation. These results indicate that the His-tag successfully controlled the orientation of the RC on the solid substrate, and that the RC produced photocurrent depending upon the orientation on the electrode.

Uterine leiomyosarcoma producing granulocyte colony stimulating factor.

Uterine leiomyosarcoma associated with the paraneoplastic production of granulocyte-colony stimulating factor (GCSF) is extremely rare. No case has been reported to date in the English literature. We describe a case of a 56-year-old female with recurrent uterin leiomyosarcoma, associated with leukocytosis (19100/mm) and an elevated serum GCSF (33.0 pg/ml). Tumore histology was consistent with a well differentiated leiomyosarcoma with marked neutrophilic infiltration of the lung and spleen metastases. tumor cells were distinctly positive for GCSF on immunohistochemistry. These findings confirmed the diagnosis of a GCSF-producting uterine leiomyosarcoma with a paraneoplastic leukocytosis.

Frequent loss of tumor suppressor ARID1A protein expression in adenocarcinomas/adenosquamous carcinomas of the uterine cervix.

OBJECTIVES: Expression of ARID1A (the adenine, thymine-rich interactive domain 1A), a putative tumor suppressor, has recently been shown to be lost in several tumor types. This study investigated whether ARID1A expression was also lost in cervical squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas. METHODS: A total of 91 patients with cervical carcinoma were enrolled. Cervical carcinoma specimens were examined for ARID1A protein expression by immunohistochemistry. The correlations between the loss of ARID1A expression and clinicopathological characteristics, and prognosis were investigated. RESULTS: Using immunohistochemistry, the frequency of loss of ARID1A expression in adenocarcinomas/adenosquamous carcinomas (31.1% [14/45]) was significantly higher than that in squamous cell carcinomas (6.5% [3/46]; P = 0.0017). There was no significant association between the loss of ARID1A expression and International Federation of Gynecology and Obstetrics staging, lymphovascular space invasion, lymph node metastasis, age, and Ki-67 LI in cervical adenocarcinomas/adenosquamous carcinomas. Loss of ARID1A expression was not correlated with shorter overall/disease-free survival in cervical adenocarcinomas/adenosquamous carcinomas. CONCLUSIONS: In conclusion, this study provides the first evidence of the frequent loss of ARID1A protein expression in cervical adenocarcinomas/adenosquamous carcinomas. No significant differences between ARID1A positive and negative cases were observed with respect to any clinicopathological features examined.

Sister Mary Joseph's nodule associated with rare endometrial squamous cell carcinoma.

BACKGROUND: Umbilical metastasis (Sister Mary Joseph's nodule) is a rare physical sign seen only in 1-3 % of patients with an intra-abdominal and/or pelvic malignancy. Here, we present a case of Sister Mary Joseph's (SMJN) nodule originating from a primary squamous cell carcinoma of the endometrium, a rare histological subtype. CASE HISTORY: SMJN was detected in a 30-year-old woman after a preoperative CT scan for a suspected umbilical hernia. Subsequent laparotomy and histopathological examination confirmed endometrial squamous cell carcinoma metastasizing to the umbilical region. CONCLUSION: The SMJN may be the first presenting sign of an intra-abdominal and/or pelvic malignancy and may co-exist with an umbilical hernia. Therefore, malignancy should be considered one of the differentials of an umbilical mass.