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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Increased apoptosis of germ cells in patients with AZFc deletions.

PURPOSE: AZFc deletions are associated with variable testicular histology ranging from the Sertoli cell only to spermatogenic arrest and hypospermatogenesis. Such variable phenotypes may be explained by progressive germ cell regression over time. Increased apoptosis is likely responsible for progressive regression of spermatogenic potential. This study evaluated germ cell apoptosis as a cause of the progressive decrease in the number of germ cells in patients with AZFc deletions. METHODS: This study evaluated germ cell apoptosis in patients with AZFc deletions. A total of 151 patients who were diagnosed with either severe oligozoospermia or non-obstructive azoospermia were screened for Y chromosome microdeletions. Germ cell apoptosis was examined using terminal deoxy-nucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) on formalin-fixed 5-microm sections of testicular specimens. RESULTS: Seven out of 117 (6.0%) patients with azoospermia and 4 of 34 (11.8%) patients with severe oligozoospermia had Y chromosome microdeletions. The percentage of apoptotic germ cells in the testes of patients with AZFc deletions were significantly increased compared to those of patients without AZFc deletions. CONCLUSIONS: These results suggest that increased apoptosis of germ cells is responsible for the progressive decline of spermatogenic potential in patients with AZFc deletions.

Extranodal Rosai-Dorfman disease involving bilateral ovaries in a patient with a ventriculoperitoneal shunt.

Rosai-Dorfman disease (RDD) is a rare condition of unknown etiology, and female genital tract involvement in RDD is uncommon. We describe the first case of RDD with bilateral ovarian involvement in a patient implanted with a ventriculoperitoneal (VP) shunt. The patient was a 17-year-old Japanese woman who had undergone radiotherapy, surgery for extranodal RDD involving the brain, and VP shunt insertion at age 12. Bilateral pelvic masses were incidentally detected on a computed tomography scan. She underwent laparotomy for lesion extirpation. On abdominal washing cytology, histiocytes showing emperipolesis were identified. Bilateral salpingo-oophorectomy was performed instead of extirpation, as it was difficult to identify the lesion margins. At 24 months after surgery, the patient is well and has not developed local recurrence. Thus, RDD can recur because of implantation of lesion cells into the abdominal cavity through a VP shunt, as is observed in the case of cerebral neoplasms.

The prevalence of hereditary breast/ovarian cancer risk in patients with a history of breast or ovarian cancer in Japanese subjects.

AIM: Women at high risk for hereditary breast/ovarian cancer require specific management strategies for cancer prevention and early detection. The authors sought to determine the prevalence of family histories suggestive of a hereditary breast/ovarian cancer syndrome in patients with a personal history of breast or ovarian cancer in Japanese women. METHODS: Family history (first- and second-degree relatives) data were collected by a self-administered questionnaire for women with a history of breast or ovarian cancer in six major cancer treating hospitals in Niigata prefecture, Japan. RESULTS: Data were obtained from 1463 women: 626 women with a history of breast cancer, 289 women with a history of ovarian cancer and 548 women without a history of any cancer as controls. Women with a family history of breast and/or ovarian cancer had OR of breast cancer of 2.3 (95% confidential interval [CI] 1.5-3.7) and ovarian cancer of 2.2 (95% CI 1.3-3.8). The risk was higher when the proband was younger or when two or more relatives were affected. Among women with a history of breast or ovarian cancer, 7.5% met the criteria for a 10% risk of a BRCA1 or BRCA2 mutation according to the Myriad model. CONCLUSION: Obtaining a detailed breast and ovarian cancer family history and the application of the Myriad model is useful for identifying women at an elevated genetic risk of breast and ovarian cancer. The estimation for the prevalence of hereditary breast/ovarian cancer syndrome has significant implications for a patient's management, as well as for the capacity for risk assessment and testing.

Association of single nucleotide polymorphisms in adiponectin and its receptor genes with polycystic ovary syndrome.

OBJECTIVE: To examine the possible association of adiponectin (ADIPOQ), adiponectin receptor (ADIPOR1/2) gene polymorphisms with polycystic ovary syndrome (PCOS) and their influence on insulin resistance in Japanese women with PCOS. STUDY DESIGN: Six single nucleotide polymorphisms (SNPs) in ADIPOQ and ADIPOR1/2 were genotyped in 59 infertile Japanese women with PCOS and 97 healthy Japanese controls. In addition, the association between the genotype and allele frequencies of these SNPs and the clinical phenotypes was analyzed in PCOS patients. RESULTS: There was no significant difference in the genotype and allele frequencies of the 6 SNPs between PCOS patients and controls. In the PCOS group, women with the GG genotype of 45T > G of ADIPOQ had a significantly higher score in the homeostasis model assessment for insulin resistance, fasting blood sugar and insulin level than those with other genotypes. Furthermore, a statistically significant difference in the genotype frequency of 45T > G polymorphism was observed between PCOS subjects with insulin resistance (n = 38) and controls (p = 0.011). CONCLUSION: The 6 SNPs of ADIPOQ and ADIPOR1/2 were not associated with a risk of PCOS. However, the 45T > G SNP in the ADIPOQ may be related to insulin resistance in Japanese women with PCOS.

Conservative treatment of stage IA1 adenocarcinoma of the cervix during pregnancy.

OBJECTIVE: The incidence of glandular neoplasms of the uterine cervix has been steadily increasing over the past 2 decades. These lesions tend to arise in women of childbearing age. Few reports have described the treatment of glandular neoplasms of the cervix in gravid women. This report describes the preliminary results of treating stage IA1 cervical adenocarcinoma by cervical conization during pregnancy. METHODS: All patients diagnosed to have FIGO stage IA1 cervical adenocarcinoma between 1990 and 2006 were reviewed and patients diagnosed during pregnancy were identified. Information was abstracted on the clinical data including the presence or absence of disease at the margins of conization, pregnancy outcome, and the follow-up. RESULTS: Sixteen patients with stage IA1 cervical adenocarcinoma were identified. Four out of the 16 patients were diagnosed during pregnancy. Four women ages 29-37 underwent KTP LASER conization and vaporization at 16 to 23 weeks' gestation. The histology showed that all of the tumors were endocervical type adenocarcinoma. None had lymph-vascular space invasion. All of these patients expressed a strong desire to continue their pregnancy. Two patients had positive conization margins for invasive cancer and underwent a second conization at 20 weeks' gestation and 5 weeks after delivery, respectively. No residual disease was identified in the second conization specimens. All patients delivered at term. One patient was treated with cervical conization alone and 3 patients were treated with an extended radical hysterectomy with pelvic lymph nodes dissection after delivery. No patient had residual invasive cancer in a subsequent surgical specimen. None of the patients had developed recurrent disease after a 2-13-year follow-up. CONCLUSION: These preliminary data suggest that patients with FIGO stage IA1 cervical adenocarcinoma may be treated conservatively by cervical conization during pregnancy. Although a hysterectomy should be considered at the completion of childbearing, fertility sparing postpartum management could be an option for selected patients.

Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced ovarian cancer.

BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced ovarian cancer (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, MRP1, MRP2 and LRP in 60 advanced ovarian cancer patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced ovarian cancer.