GnRH agonist pre-treatment for microwave endometrial ablation in women with less than 1 centimetre myometrial thickness.

We evaluated the efficacy of gonadotropin-releasing hormone agonist (GnRHa) therapy for improving the myometrial thickness in women with thin (less than 1 cm) uterine walls, a contraindication for microwave endometrial ablation (MEA). The normal myometrium thickness was 0.5 cm, 0.7 cm and 0.9 cm. After the third GnRHa dose, the myometrial thickness increased to over 1 cm in all the three patients, and all were able to undergo MEA. The VAS score for menorrhagia improved in all the cases. The patient satisfaction levels were 10 in 2 of the 3 patients, and 5 in the other. There was no symptom recurrence, and no adjuvant therapy was administered. GnRHa therapy in women with submucous leiomyomata and a myometrial thickness of less than 1 cm could effectively thicken the myometrium, allowing for the use of MEA.

Letrozole as second-line hormonal treatment for recurrent low-grade endometrial stromal sarcoma: A case report and review of the literature.

Low-grade endometrial stromal sarcoma (LGESS) is a rare malignancy. The tumor is reportedly responsive to hormonal therapy, most commonly with medroxyprogesterone acetate (MPA), but the effectiveness of aromatase inhibitors for recurrent LGESS remains unclear. The present study reports a case of stage IC LGESS presenting with abnormal uterine bleeding, and also provides a review of the literature. Following a total abdominal hysterectomy and bilateral salpingo-oophorectomy, MPA therapy was initiated; treatment was successful, but discontinued 19 months later due to disruptive side effects. A further 2 months later, the patient presented with recurrent disease and received chemotherapy. MPA treatment was restarted with a partial response. A second recurrence, 4 years later, presented with lung and para-aortic lymph node metastases. The patient responded to treatment with the aromatase inhibitor letrozole. The patient has since exhibited stable disease and remained free of symptoms for 7 years. This case suggests that aromatase-inhibitor treatment may be effective for recurrent LGESS as a second-line treatment.

Efficacy of multiple microwave endometrial ablation technique for menorrhagia resulting from adenomyosis.

AIM: Conventional microwave endometrial ablation (MEA) can be insufficient to control menorrhagia resulting from adenomyosis. We compared the standard single ablation technique with multiple MEA - repeating ablation three times in the same region - in patients with adenomyosis and menorrhagia. MATERIAL AND METHODS: We performed single MEA in 18 patients and multiple MEA in seven patients between 2007 and 2013. We compared the efficacy of single and multiple MEA using a visual analog scale (VAS) for menorrhagia, dysmenorrhea, and patient satisfaction. We also evaluated the incidence of menorrhagia recurrence, amenorrhea, and procedure complications in relation to patients' clinical factors. RESULTS: VAS scores for improved menorrhagia and patient satisfaction were significantly higher in the multiple MEA group than in the single MEA group; however, the operative time was longer in the multiple-treatment group. There were no statistical differences between groups in hemoglobin levels, VAS improvement for dysmenorrhea, menorrhagia recurrence, frequency of complications, or amenorrhea rate. CONCLUSION: Multiple MEA successfully controls menorrhagia from adenomyosis and achieves a higher satisfaction rate than single MEA.

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.

ESR1 gene amplification in endometrial carcinomas: a clinicopathological analysis.

This study investigated the clinicopathological significance of estrogen receptor 1 (ESR1) gene amplification and its relationship to phosphatase and tensin homolog (PTEN), human epidermal growth factor receptor 2 (HER2), MutL homolog 1 (MLH1), p53, and AT rich interactive domain 1A (ARID1A) expression in endometrial carcinomas. ESR1 amplification and expression were assessed by fluorescence in situ hybridization and immunohistochemistry. Clinical data were collected by retrospective chart review. ESR1 amplification was identified in 13 out of 111 (11.7%) endometrial carcinomas. No significant association was observed between ESR1 amplification and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.17), histological grade (p=0.35), lymph node metastasis (p=0.51), or deep myometrial invasion (p=0.46). ESR1 amplification was independent of PTEN, p53, HER2, MLH1, and ARID1A protein expression. Patients without estrogen receptor (ER) or progesterone receptor (PR) expression had shorter progression-free and overall survival than those with ER or PR expression (p<0.01). ESR1 amplification is independent of known clinicopathological factors related to poor prognosis and PTEN, p53, HER2, MLH1, and ARID1A protein expression, suggesting ESR1 amplification may be an early event in endometrial carcinoma development.

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.

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.

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.

PPP2R1A mutation is a rare event in ovarian carcinoma across histological subtypes.

Somatic mutations in PPP2R1A, which encodes a scaffolding subunit of serine/threonine protein phosphatase 2A (PP2A), have recently been described in different types of gynecological neoplasias. To extend this observation, we examined the frequency of PPP2R1A mutation in some major histological subtypes of type I and type II ovarian carcinoma. Mutational analysis of PPP2R1A (exons 5 and 6) was performed on 88 primary ovarian carcinomas, including mucinous, clear cell, high-grade serous, and high-grade endometrioid ovarian carcinoma. In addition, exons 9 and 20 of Phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA), exon 1 of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and exon 15 of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) were sequenced and compared across the different histological subtypes. Finally, survival analysis was performed to determine any prognostic significance of these mutations. Mutations in PPP2R1A were rare: detected in 4.5% (1/22) of clear cell, 4.5% (1/22) of high-grade serous, and 6.7% (1/15) of high-grade endometrioid ovarian carcinoma. Interestingly, no PPP2R1A mutations were observed in mucinous ovarian carcinoma. A higher frequency of PIK3CA mutations (50%, 11/22) was found in clear cell carcinoma and a higher frequency of KRAS mutations (24.1%, 7/29) was observed in mucinous carcinoma. In addition, high-grade endometrioid ovarian carcinoma exhibited KRAS and PIK3CA mutations in 26.7% (4/15) and 20% (3/15) of cases, respectively. Survival analysis showed no significant association between mutational status and overall survival of patients. This study indicates that the PPP2R1A mutation occurs at a lower frequency compared to other gynecological malignancies, irrespective of the histological subtype.

Clinicopathologic analysis of loss of AT-rich interactive domain 1A expression in endometrial cancer.

Loss of the AT-rich interactive domain 1A (a putative tumor suppressor) protein BAF250a has recently been described as a frequent event in endometrial carcinoma. In this study, we determined the significance of the loss of AT-rich interactive domain 1A immunoreactivity for several clinicopathologic features of uterine endometrioid carcinoma. AT-rich interactive domain 1A expression was assessed by immunohistochemistry using 111 paraffin-embedded tissue specimens and clinical data collected by a retrospective medical record review. The correlations between loss of AT-rich interactive domain 1A protein and clinicopathologic and prognostic features were examined. In addition, the expression of PTEN, p53, Her2, and MLH1 was assessed by immunohistochemistry and compared with AT-rich interactive domain 1A expression. AT-rich interactive domain 1A immunoreactivity was undetectable in 27 (24%) of 111 analyzed endometrioid endometrial carcinomas. There was no significant difference between negative and positive cases of AT-rich interactive domain 1A in terms of any clinicopathologic features examined (International Federation of Gynecology and Obstetrics stage, grade, depth of myometrial invasion, lymph node metastasis, lymphovascular space invasion, body mass index, postmenopausal status, patient age at diagnosis, and estrogen and progesterone receptor status). The comparison between the expression of AT-rich interactive domain 1A and the expression of PTEN, p53, Her2, and MLH1 also revealed no significant association. There was no significant correlation between AT-rich interactive domain 1A expression and progression-free/overall survival of patients. This study provides the first examination of the clinicopathologic relationship between AT-rich interactive domain 1A protein expression and endometrial carcinoma. No significant differences between positive and negative cases of AT-rich interactive domain 1A were observed with respect to any clinicopathologic features or patient survival.

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.

Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer.

This study examined the clinical significance of Notch3 expression and assessed its usefulness as a potential therapeutic target in chemoresistant ovarian cancer. Notch3 expression was assessed with immunohistochemical examination, and clinical variables were collected with a retrospective chart review. Notch3 siRNA or γ-secretase inhibitor was used to assess Notch3 function in ovarian cancer cell lines. Notch3 overexpression correlated with shorter progression-free/overall survival in patients with advanced stage (stage III, IV) ovarian carcinoma treated with platinum and taxane. Three of 5 patients showed increased Notch3 immunostaining in recurrent tumors compared with corresponding primary tumors. Notch3 overexpression was observed in both the cisplatin-resistant KFr13 and cisplatin/paclitaxel-resistant KFr13Tx cells. Inactivation of Notch3 by γ-secretase inhibitor or siRNA decreased cell proliferation and induced apoptosis in the KFr13 and KFr13Tx cells. Our findings suggest that Notch3 expression may be related to chemoresistance and that the Notch3 pathway may represent a novel therapeutic target for advanced stage chemoresistant ovarian cancer.

NAC1, a BTB/POZ protein overexpressed in uterine sarcomas.

BACKGROUND: The purpose of this study was to investigate the role of Nucleus accumbens-associated 1 (NAC1) in the development of uterine sarcomas. MATERIALS AND METHODS: NAC1 expression and localization in the normal myometrium, benign leiomyoma, and uterine sarcoma were assessed with immunohistochemistry. NAC1-specific siRNA was used to inactivate NAC1 for in vitro biological assays. RESULTS: Almost all cases of uterine sarcoma were found to overexpress NAC1. Expression of NAC1 was significantly higher in uterine sarcomas than in benign leiomyomas (p<0.0001). NAC1 gene knockdown inhibited cell growth and induced apoptosis in SKN, a leiomyosarcoma cell line, and in OMC-9, an endometrial stromal sarcoma cell line, both of which overexpress NAC1. CONCLUSION: Uterine sarcomas with NAC1 overexpression are clinically the most aggressive, chemoresistant, and radioresistant tumors. Therefore, detection of NAC1 overexpression in uterine sarcomas may identify patients who will benefit from NAC1-targeted therapy.

Gene amplification of ZNF217 located at chr20q13.2 is associated with lymph node metastasis in ovarian clear cell carcinoma.

BACKGROUND: Recently we reported that amplification of the Zinc Finger Protein 217 (ZNF217) gene adversely affects survival of patients with ovarian clear cell carcinoma. This study sought to determine the mechanism by which ZNF217 amplification affects patient survival. MATERIALS AND METHODS: Fluorescence in situ hybridization (FISH) was used to detect ZNF217 gene amplification status and ZNF217-specific siRNA was used to inactivate ZNF217 for in vitro biological analyses. RESULTS: We found ZNF217 gene amplification to be significantly correlated with lymph node metastasis (p<0.05) in ovarian clear cell carcinoma. Profound inhibition of cell migration and invasion was observed in siRNA-treated cells with ZNF217 amplification, compared to cells without amplification. CONCLUSION: These findings provide new insight into the biological role of ZNF217 gene amplification in ovarian clear cell carcinoma. Additionally, our observations have an important therapeutic implication for patients with ovarian clear cell carcinomas with ZNF217 amplification, as these patients may potentially benefit from ZNF217 targeted-therapy.

Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma.

Somatic mutations of PIK3CA (phosphoinositide-3-kinase) have recently been shown playing an important role in the pathogenesis of ovarian clear cell carcinoma. In this study, the frequency of PIK3CA mutations and the relationship of PIK3CA mutations with clinicopathologic and biological variables were investigated in ovarian clear cell carcinomas from Japanese patients. Mutational analysis of PIK3CA was performed in 56 primary ovarian clear cell carcinomas from Japanese women. The relationship of these mutations with various clinicopathologic and biological variables (phosphorylated AKT and phosphorylated mTOR (mammalian target of rapamycin) expression by immunohistochemistry) was determined. To clarify the roles of PI3K/AKT activation in ovarian clear cell carcinomas harboring PIK3CA mutations, we inactivated the PI3K/AKT/mTOR pathway in ovarian carcinoma cells with LY294002, temsirolimus and NVP-BEZ235. Missense mutations of PIK3CA were found in 16 (28.6%) of 56 ovarian clear cell carcinomas, but no mutation was found in 15 ovarian high-grade serous carcinomas. PIK3CA mutations were significantly associated with a favorable overall survival of patients with ovarian clear cell carcinoma (P < .05). There was no significant association between PIK3CA mutations and phosphorylated AKT or phosphorylated mTOR immunointensity status. No relationship was found between PIK3CA mutation status and sensitivity to PI3K/AKT/mTOR inhibitors in ovarian clear cell carcinoma cells. No association of PIK3CA mutations was found between positive phosphorylated AKT and positive phosphorylated mTOR, which suggests that the PI3K/AKT/mTOR pathway may be activated by other molecular mechanisms. Although PIK3CA mutations were associated with a more favorable prognosis, they did not predict the sensitivity of ovarian clear cell carcinoma cells to PI3K/AKT/mTOR inhibitors.

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.

[A case of stage IVb cervical carcinoma in which survival was prolonged by two different chemotherapies and CCRT].

Pulmonary metastasis from primary cervical carcinoma is rare, with an incidence of 4.16-7.7%. Chemotherapy is the most common treatment; however, the overall prognosis is poor. This case report describes a complete response to CCRT and TC therapy of cervical carcinoma metastatic to the lung. The patient, a 57-year-old woman, was initially diagnosed with FIGO clinical Stage IVb cervical carcinoma with lung metastasis, after presenting with vaginal bleeding. She had a 90 pack/year smoking history. She was initially treated with systemic chemotherapy(TC therapy: PTX, CBDCA 1 course)followed by concurrent chemoradiotherapy(CCRT)with weekly CDDP2 0mg/m2. She had a complete response of her pelvic disease as well as a decrease in the size of metastatic lesions. Following CCRT, she was scheduled to continue TC therapy, but was only able to complete two courses secondary to a myocardial infarction. A lung biopsy at that time showed no evidence of malignancy, and the patient has remained without any evidence of disease for the past six years.

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.

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.