Acute psychiatric symptoms in a young woman with anti-N-methyl D-aspartate receptor encephalitis: A case of successful early diagnosis and therapeutic intervention.

This clinical image presents a report on the diagnosis and treatment of anti-NMDAR encephalitis, a rare disease. This report emphasizes the importance of a differential diagnosis for acute psychiatric symptoms. Accurate and timely diagnosis is critical for the selection and implementation of treatment and for optimal patient outcomes.

Gestational choriocarcinoma: Rare spinal metastasis during a viable pregnancy.

Gestational choriocarcinoma metastasizing to the bones, especially to the spine, is extremely rare. In addition, there are few reports of choriocarcinoma during a viable pregnancy. We report a case of gestational choriocarcinoma that metastasized to the lumbar spine during a viable pregnancy in a 41-year-old woman with a history of a missed abortion. A heterogeneous cervical mass was detected at gestational week 16. Subsequently, a metastatic lesion appeared during the pregnancy, and fetal demise in utero occurred. Pathological examination revealed that the cervical tumor and metastatic spinal tumor were choriocarcinoma. The patient's condition deteriorated rapidly and we were unable to save her life, despite multidrug chemotherapy. Surgical tumor resection and pregnancy might involve a substantial risk of choriocarcinoma metastasis. It is important to obtain an early diagnosis for this life-threatening disease in order to facilitate appropriate treatment, despite pregnancy.

A phase II study of paclitaxel and carboplatin with a biweekly schedule in patients with epithelial ovarian cancer: Gynecologic Cancer Network trial.

AIM: The objective of this multicenter phase II study was to evaluate the effects of biweekly paclitaxel and carboplatin combination chemotherapy on response rate and toxicities in patients with epithelial ovarian cancer. PATIENTS AND METHODS: Patients with International Federation of Gynecology and Obstetrics stage II to IV ovarian cancer received paclitaxel at a dose of 120 mg/m(2) and carboplatin at an area under the curve of 3 mg/mL per minute every 2 weeks for 8 or more cycles. Inclusion criteria included an Eastern Cooperative Oncology Group performance status of 0 to 2 and no previous chemotherapy. Informed consent was obtained from each patient before the start of treatment. RESULTS: From March 2003 through July 2009, 42 patients from 5 institutions were eligible to be evaluated for response and toxicity. The median age was 60.5 years (age range, 34-81 years). The International Federation of Gynecology and Obstetrics stage was stage II in 3 patients, stage III in 31 patients, and stage IV in 8 patients. The response rate was 66.7% (95% confidence interval: 50.5%-80.4%). Sixty-nine percent (29 of 42) of patients received 8 or more cycles of chemotherapy. The median progression-free survival was 18.5 months, and overall survival was 59.1 months. The most common grade 3 or 4 hematological toxicity was neutropenia (61.0%). No patients had grade 3 or 4 thrombocytopenia. The most common grade 3 nonhematological toxicities were neuropathy (4.9%) and nausea (2.4%). CONCLUSION: Paclitaxel combined with carboplatin using a biweekly schedule is a safe and effective chemotherapy regimen for patients with epithelial ovarian cancer. Our results suggest that a biweekly schedule is well tolerated and is less toxic than a triweekly schedule.

Promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A genes in cervical carcinoma.

BACKGROUND AND OBJECTIVES: Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of human cancer. This study explored the relationship between promoter methylation and inactivation of the DAPK1, FHIT, MGMT, and CDKN2A genes in cervical cancer. METHODS: The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens. The correlation of promoter methylation with the clinicopathological features of cervical cancer was analyzed. The expressions of DAPK1, FHIT, MGMT, and CDKN2A were detected by measuring relative mRNA levels. RESULTS: The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A in cervical cancer vs. intraepithelial neoplasia vs. normal cervical tissue was 75.5 vs. 31.8 vs. 4.2 % (p < 0.0001), 66.0 vs. 59.1 vs. 25.0 % (p = 0.0033), 34.0 vs. 27.3 vs. 20.8 % (p = 0.76), and 17.0 vs. 31.8 vs. 8.3 % (p = 0.11), respectively. The methylation of the promoter region significantly decreased the expression of only DAPK1 (p = 0.03). The methylation rate of the DAPK1 gene promoter was significantly higher in cervical cancer tissues than in cervical intraepithelial neoplasia and normal cervical tissues. CONCLUSION: Promoter methylation may therefore lead to the inactivation of the DAPK1 gene, and may be related to the progression of cervical oncogenesis.

A nonsynonymous variant of IL1A is associated with endometriosis in Japanese population.

Our previous genome-wide association study has demonstrated that single-nucleotide polymorphisms (SNPs) located in intronic and downstream regions of IL1A (interleukin 1α) were associated with the risk of endometriosis. These SNPs on the genome-wide association study platform could be only surrogates for the true causal variant. Thus, we resequenced all the exons of IL1A in 377 patients with endometriosis and 457 healthy controls. We detected seven rare variants (minor allele frequency <0.01) and four common variants. All the rare variants were not associated with endometriosis. The four common variants (rs17561, rs1304037, rs2856836 and rs3783553) in IL1A were significantly associated with endometriosis (P=0.0024, 0.0024, 0.0014 and 0.0061, respectively). All the four SNPs were within a linkage disequilibrium block. Among them, only rs17561 was nonsynonymous (p.A114S), which has been reported to be associated with susceptibility to ovarian cancer. Taken together, we examined association between rs17561 and endometriosis in an independent validation data set (524 patients and 533 healthy controls) replicating significant association (P=4.0 × 10(-5); odds ratio (OR), 1.91; 95% confidence interval (CI), 1.41-2.61). Meta-analysis by combining results from the two stages strengthened the evidence of association (P=2.5 × 10(-7); OR, 1.90; 95% CI, 1.49-2.43). Our findings demonstrated that the nonsynonymous variant of IL1A might confer genetic susceptibility to endometriosis in Japanese population.

Outcomes of fertility-sparing surgery for women of reproductive age with FIGO stage IC epithelial ovarian cancer.

OBJECTIVE: To report the clinical outcomes of patients with FIGO stage IC epithelial ovarian cancer (EOC) treated by fertility-sparing surgery (FSS). METHODS: A retrospective review was conducted of 18 women who underwent FSS at Niigata University Hospital, Japan, between December 15, 1986, and December 31, 2010. RESULTS: Tumors were mucinous (n=9), clear cell (n=4), endometrioid (n=3), and serous (n=2). Median follow-up was 78.0 months (range, 9.3-181.3 months). Five patients (27.8%) developed tumor recurrence at 7.4-19.2 months after initial surgery. The sites of recurrence were peritoneal lymph nodes (n=2), contralateral ovary (n=1), contralateral ovary and peritoneal cavity (n=1), and brain (n=1). In all, 7 full-term singleton pregnancies were recorded among 5 of the 10 women who attempted to conceive after FSS. CONCLUSION: Favorable reproductive outcomes were observed following FSS, suggesting that this procedure may be a valid treatment option for women with FIGO stage IC EOC who wish to conceive.

Polycystic ovary syndrome: association of a C/T single nucleotide polymorphism at tyrosine kinase domain of insulin receptor gene with pathogenesis among lean Japanese women.

OBJECTIVE: To assess whether the insulin receptor (INSR) gene contributes to genetic susceptibility to polycystic ovary syndrome (PCOS) in a Japanese population. STUDY DESIGN: We ex-amined the frequency of the His 1058 C/T single nucleotide polymorphism (SNP) found in exon 17 of the INSR gene in 61 Japanese PCOS patients and 99 Japanese healthy controls. In addition, we analyzed the association between the genotype of this SNP and the clinical phenotypes. RESULTS: The frequency of the C/C genotype was not significantly different between all PCOS patients (47.5%) and controls (35.4%). However, among the lean cases (body mass index < or = 20 kg/m2) the frequency of the C/C genotype was significantly increased (p < 0.05) in PCOS patients (65.0%) as compared with controls (36.6%). CONCLUSION: We concluded that the His 1058 C/T polymorphism at the tyrosine kinase domain of the INSR gene had a relationship to the pathogenesis of lean PCOS patients in a Japanese population.

Ovarian pregnancy resulting from cryopreserved blastocyst transfer.

Ovarian pregnancy very rarely occurs and its exact mechanism is unclear. Here, we report a case of ovarian pregnancy resulting from cryopreserved blastocyst transfer. The patient was a 34-year-old woman who had undergone bilateral ovarian cystectomy for endometriosis. Both fallopian tubes indicated normal findings on laparoscopic surgery, and we removed the gestational product of the right ovary. Pathological analysis confirmed the diagnosis of right ovarian pregnancy. Ectopic pregnancy is one of the major complications of in vitro fertilization-embryo transfer. Although ovarian pregnancy is an extremely rare occurrence, the possibility of developing this event after cryopreserved blastocyst transfer should be recognized.

Possible involvement of the E-cadherin gene in genetic susceptibility to endometriosis.

BACKGROUND: Endometriotic cells display invasive characteristics, despite their benign histological appearance. Recently, the epithelial-mesenchymal transition, in which epithelial cells acquire mesenchymal and migratory properties, has attracted attention as a mechanism of tumor invasion. We aimed to investigate the association between endometriosis and polymorphisms of the E-cadherin gene, a central player in the epithelial-mesenchymal transition, in Japanese women. METHODS: Twelve single-nucleotide polymorphisms (SNPs) in the E-cadherin gene were identified by real-time polymerase chain reaction using a TaqMan assay in 511 women with endometriosis (the majority in Stages III and IV) and 498 healthy controls. RESULTS: Allele frequency analysis indicated that there was a marginally higher frequency of the rs4783689 C allele in women with endometriosis compared with controls (corrected P = 0.007; odds ratio = 1.37; 95% confidence interval, 1.14-1.64). No significant associations with endometriosis were found for the other 11 SNPs. CONCLUSIONS: Although this study was limited by sample size, the E-cadherin gene polymorphism rs4783689 was marginally associated with endometriosis in the Japanese population, suggesting that E-cadherin might be involved in genetic susceptibility to endometriosis.

Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: a population-based study from 1983 to 2007 in Niigata.

AIM: The histology-specific long-term trends in the incidence of ovarian cancer and borderline tumors in Japanese women were examined, based on data from the population-based cancer registry in Niigata, Japan. MATERIAL AND METHODS: Data were obtained from the Niigata Gynecological Cancer Registry, which covered the entire female population in Niigata prefecture, Japan, during the period from 1983 to 2007. RESULTS: A total of 3134 females with epithelial ovarian cancer, including borderline tumor cases, were diagnosed between 1983 and 2007. The age-standardized rates (ASRs) of both ovarian cancer and borderline tumors have steadily increased, with significant changes in ovarian cancer in all age groups, and borderline ovarian tumors in subjects aged <50. The ASRs of endometrioid adenocarcinoma showed a steady increasing trend, and those of clear cell and mucinous adenocarcinomas showed significant increasing trends in the total population. The ASRs of clear cell, mucinous, and endometrioid adenocarcinomas in the 50+ age group were significantly increased, especially the incidence of clear cell adenocarcinoma, which strikingly increased by approximately threefold from 1.2 (1983-1989) to 3.5 (2000-2007) per 100,000 females. CONCLUSION: This prefecture-wide study showed the practical trends in ovarian cancer and borderline tumors in Japanese females. The incidence of ovarian cancer has steadily increased, with significant increases in the incidence of clear cell and mucinous adenocarcinomas in the total population during the past two decades. Because of the poor response rate of these histological subtypes to platinum-based regimens, novel treatment approaches should be adopted to improve the prognostic outcome in patients with ovarian cancer in Japan.

Identification of receptor tyrosine kinase, discoidin domain receptor 1 (DDR1), as a potential biomarker for serous ovarian cancer.

Ovarian cancer, one of the most common gynecological malignancies, has an aggressive phenotype. It is necessary to develop novel and more effective treatment strategies against advanced disease. Protein tyrosine kinases (PTKs) play an important role in the signal transduction pathways involved in tumorigenesis, and represent potential targets for anticancer therapies. In this study, we performed cDNA subtraction following polymerase chain reaction (PCR) using degenerate oligonucleotide primers to identify specifically overexpressed PTKs in ovarian cancer. Three PTKs, janus kinase 1, insulin-like growth factor 1 receptor, and discoidin domain receptor 1 (DDR1), were identified and only DDR1 was overexpressed in all ovarian cancer tissues examined for the validation by quantitative real-time PCR. The DDR1 protein was expressed in 63% (42/67) of serous ovarian cancer tissue, whereas it was undetectable in normal ovarian surface epithelium. DDR1 was expressed significantly more frequently in high-grade (79%) and advanced stage (77%) tumors compared to low-grade (50%) and early stage (43%) tumors. The expression of the DDR1 protein significantly correlated with poor disease-free survival. Although its functional role and clinical utility remain to be examined in future studies, our results suggest that the expression of DDR1 may serve as both a potential biomarker and a molecular target for advanced ovarian cancer.

Complete hysteroscopic resection of a large atypical polypoid adenomyoma, followed by a successful pregnancy.

OBJECTIVE: To describe the hysteroscopic resection of a large atypical polypoid adenomyoma (APA) in a young patient followed by a successful pregnancy. DESIGN: Case report. SETTING: Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital, Niigata, Japan. PATIENT(S): A 29-year-old female who had an endocervical tumor 4 cm in size and a diagnosis of APA. INTERVENTION(S): Conservative hysteroscopic resection of the lesion. MAIN OUTCOME MEASURE(S): Disease and pregnancy outcome. RESULT(S): The lesion was completely resected by a pathologically guided, hysteroscopic surgery. The patient spontaneously became pregnant and gave birth by vaginal delivery and is free from disease 3 years after the surgery. CONCLUSION(S): Conservative hysteroscopic surgery may be a good treatment option for APA in patients who wish to preserve their fertility, even for patients with a large lesion.

Resolution of uterine arteriovenous malformation and successful pregnancy after treatment with a gonadotropin-releasing hormone agonist.

BACKGROUND: Uterine arteriovenous malformations are a rare and potentially life-threatening condition. Medical therapy has not been popular because of the propensity for excessive bleeding in the patient. As a result, the effect of gonadotropin-releasing hormone (Gn-RH) agonists on uterine arteriovenous malformations has not been established. CASE: A 30-year-old patient presented with persistent vaginal bleeding. Based on the color Doppler ultrasound and magnetic resonance imaging findings, a uterine arteriovenous malformation was diagnosed. Because initial treatment with methylergonovine maleate was unsuccessful, the patient was treated with Gn-RH agonists. The lesion completely disappeared after 6 months of Gn-RH agonist treatment. Five months after the completion of Gn-RH agonist therapy, the patient conceived spontaneously and successfully completed a normal pregnancy. The patient has remained free from recurrence of the lesion. CONCLUSION: Gonadotropin-releasing hormone agonist therapy has the potential to be a conservative treatment modality for uterine arteriovenous malformations in hemodynamically stable patients.

Germline copy number variations in BRCA1-associated ovarian cancer patients.

We investigated characteristics of germline copy number variations (CNV) in BRCA1-associated ovarian cancer patients by comparing them to CNVs present in sporadic ovarian cancer patients. Germline CNVs in 51 BRCA1-associated, 33 sporadic ovarian cancer patients, and 47 healthy women were analyzed by both signal intensity and genotyping data using the Affymetrix Genome-Wide Human SNP Array 6.0. The total number of CNVs per genome was greater in the sporadic group (median 26, range 12-34) than in the BRCA1 group (median 21, range 11-35; post hoc P < 0.05) or normal group (median 20, range 7-32; post hoc P < 0.05). While the number of amplifications per genome was higher in the sporadic group (median 13, range 7-26) than in the BRCA1 group (median 8, range 3-23; post hoc P < 0.001), the number of deletions per genome was higher in the BRCA1 group (median 12, range 6-24) than in the sporadic group (median 9, range 3-17; post hoc P < 0.01). In addition, 31 previously unknown CNV regions were present specifically in the BRCA1 group. When we performed pathway analysis on the 241 overlapping genes mapped to these novel CNV regions, the 'purine metabolism' and '14-3-3-mediated signaling' pathways were over-represented (Fisher's exact test, P < 0.01). Our study shows that there are qualitative differences in genomic CNV profiles between BRCA1-associated and sporadic ovarian cancer patients. Further studies are necessary to clarify the significance of the genomic CNV profile unique to BRCA1-associated ovarian cancer patients.

Preoperative transvaginal ultrasound guided needle biopsy for primary squamous cell carcinoma of the endometrium.

Primary squamous cell carcinoma of the endometrium (PSCCE) is an extremely rare tumor and little information is available about its treatment and prognosis. We report a case of PSCCE diagnosed with preoperative transvaginal ultrasound guided needle biopsy. A 73-year-old woman presented with prolonged abdominal pain. Her endometrium was found to be slightly thickened, and endometrial biopsy showed no carcinoma tissues. Magnetic resonance imaging (MRI) demonstrated a uterine tumor and transvaginal ultrasound guided needle biopsy specimens of the tumor showed squamous cell carcinoma. The patient underwent laparotomy and was given a diagnosis of PSCCE in International Federation of Gynecology and Obstetrics (FIGO) stage IIIa. After the operation, the patient was treated with concurrent chemoradiation therapy (CCRT) using cisplatin. She remains free of disease at 6 months after CCRT. Preoperative needle biopsy may be helpful to make a diagnosis of PSCCE.

Serum leptin-adiponectin ratio and endometrial cancer risk in postmenopausal female subjects.

OBJECTIVE: Obesity is a well-known risk factor for the development of endometrial cancer. Elevated endogenous estrogen and insulin resistance are recognized to be major factors that link obesity and cancer development. However, there is increasing evidence that the adipokines adiponectin and leptin, which are directly produced in adipose tissue, impact several obesity-related cancers. The purpose of the current study was to investigate the relationships of the concentration of leptin, adiponectin, and the leptin-to-adiponectin ratio (L/A ratio) with the endometrial cancer risk in postmenopausal female subjects. METHODS: A case-control study was performed in 146 postmenopausal female subjects with endometrial cancer and 150 control subjects with no history of cancer. The serum levels of the adipokines leptin and adiponectin were measured, and the associations of these adipokines and the L/A ratios with the endometrial cancer risk were analyzed. RESULTS: The leptin levels and the L/A ratios were significantly higher in the incident cases of endometrial cancer (8.2 ± 0.5, 2.05 ± 1.08 ng/ml) than in the controls subjects (4.5 ± 0.5, 0.98 ± 0.18, P<0.0001), whereas the adiponectin levels were significantly lower in the incident cases (6.2 ± 0.4 µg/ml) than in the control subjects (9.0 ± 0.4 µg/ml, P<0.0001). For the incident cases, the serum levels of the adipokines were significantly correlated with the patient body mass index (BMI) (P<0.001 for leptin, P<0.05 for adiponectin), and the leptin levels and the L/A ratios were significantly correlated with the homeostasis model assessment ratio (HOMA-R) and the fasting insulin levels (P<.001). Higher L/A ratios were found to be significantly associated with an increased risk of endometrial cancer [OR (95% CI) for the top vs. the bottom tertile of the L/A ratio was 6.0 (3.2-11.9), P-value<0.0001]. Moreover, the ORs of the L/A ratios were higher than those of leptin or adiponectin alone. The association of the L/A ratios with endometrial cancer risk remained after adjusting for the obesity indices, hypertension, and presence of diabetes mellitus. CONCLUSION: The present results suggested that the L/A ratio was independently associated with an increased risk for endometrial cancer development. Additional research will elucidate the molecular mechanisms by which these adipokines are associated with the development of endometrial cancer.

Conservative treatment of stage IA1 adenocarcinoma of the uterine cervix with a long-term follow-up.

OBJECTIVES: The adenocarcinoma of the uterine cervix tends to arise in women of childbearing age. Conservative treatment by conization is an alternative to a hysterectomy that allows future pregnancy; however, much less is known about the management of adenocarcinoma because of its rarity and relatively short time frame of follow-up. The purpose of this study was to determine the long-term outcome of patients treated by conization alone. METHODS: All patients diagnosed to have FIGO (International Federation of Gynecology and Obstetrics) stage IA1 cervical adenocarcinoma between 1990 and 2004 with more than 5 years' follow-up at 2 institutions were reviewed. Information was abstracted on clinical data including margin status of conization and recurrence. RESULTS: Twenty-seven patients were identified, and 10 patients who expressed a strong desire to preserve fertility were offered a conization and careful surveillance without hysterectomy. The median age was 35 years, and 40% were nulliparous. All tumors were endocervical-type adenocarcinoma, and all tumors were grade 1. None had lymphovascular space invasion. Two patients had a repeated conization because of a positive margin. No recurrence was observed during an average follow-up of 75 months. CONCLUSIONS: Although further studies on the management of microinvasive cervical adenocarcinoma are desirable, conization seems to be acceptable treatment modality for patients with stage IA1 cervical adenocarcinoma who desire to preserve their fertility. A careful and long-term follow-up is needed because of lack of sufficient evidence for the safety of this treatment.

Analysis of the complications after radical hysterectomy for stage IB, IIA and IIB uterine cervical cancer patients.

AIM: This study was undertaken to assess whether radical hysterectomy and pelvic lymphadenectomy could be carried out within acceptable complications in uterine cervical cancer patients. MATERIAL & METHODS: One hundred and forty-six patients of the International Federation of Gynecology and Obstetrics stage IB, IIA and IIB cervical cancer treated by radical hysterectomy or combined with postoperative radiation therapy were enrolled in this study. The study population was 41 women over the age of 60 and 105 women under the age of 59. Complications after the treatment of all patients were examined. RESULTS: The complications were significantly high with the patients over the age of 60 (53.7%) in comparison with the patients under the age of 59 (24.8%). Especially, the cases combined with radiation therapy had higher complication rate. The most commonly recorded complications were lymphedema (13.7%) and small bowel obstruction (8.2%). CONCLUSION: We conclude that the complications influenced on the quality of life were more frequent in patients over the age of 60.

Antituberculosis treatment for a patient with massive ascites: the role of f-18-fluorodeoxyglucose positron emission tomography.

BACKGROUND: The diagnosis of peritoneal tuberculosis (TB) is difficult, and the condition is often misdiagnosed as advanced ovarian cancer. The clinical discrimination is important to avoid both unnecessary surgery and a delay in anti-TB treatment. CASE: A 66-year-old woman presented with abdominal distension. Positron emission tomography (PET) with F18-fluorodeoxyglucose showed a diffuse F18-fluorodeoxyglucose accumulation on the entire peritoneum. The presumptive diagnosis was peritoneal TB, and anti-TB treatment was thus started. Follow-up F18-fluorodeoxyglucose-PET revealed the disappearance of the pathologic foci and a decreased peak standardized uptake value. CONCLUSION: F18-fluorodeoxyglucose-PET may be a helpful tool in the diagnosis of peritoneal TB and serial F18-fluorodeoxyglucose-PET plays a potentially important role in monitoring the treatment response. The peak standardized uptake value may also be helpful for making a quantitative assessment of the therapeutic response.

Gene expression profile for predicting survival in advanced-stage serous ovarian cancer across two independent datasets.

BACKGROUND: Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. METHODOLOGY/PRINCIPAL FINDINGS: Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66-5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20-1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). CONCLUSIONS/SIGNIFICANCE: The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.