Long-term outcomes of photodynamic therapy for a positive resection margin after conization for cervical intraepithelial neoplasia grade 3.

BACKGROUND: Positive resection margins after conization or loop electrosurgical excision procedure (conization/LEEP) are associated with increased risks of recurrence or residual cervical intraepithelial neoplasia (CIN). Herein, we investigated the long-term outcomes of photodynamic therapy (PDT) for incomplete excision of CIN3. METHODS: We retrospectively reviewed the medical charts of 73 patients treated with PDT between 2000 and 2011. Patients who underwent conization/LEEP before PDT within 6 months were included. The primary outcomes were the complete response (CR) rate after 1 year and human papillomavirus (HPV) eradication rate at 6 months after PDT. RESULTS: A total of 34 patients with positive resection margins were finally enrolled. The median patient age was 33 years. Carcinoma in situ was diagnosed in 25 patients and CIN3 in 7 patients. The CR rate was 97.1% after 1 year. Except for one case of a persistent disease, there was no recurrence or newly developed disease during the median follow-up of 84 months (range, 12-224 months). The HPV eradication rate of PDT following conization/LEEP after 6 months was 96.9% (31/32). Photosensitivity was identified in five patients and cervical stenosis in one patient. CONCLUSIONS: In conclusion, PDT could be an effective therapeutic option for patients with a positive resection margin after conization/LEEP for CIN3. It could reduce the residual or recurrence rate of CIN lesions with tolerable adverse events.

Antitumor Effects of Selenium.

Functions of selenium are diverse as antioxidant, anti-inflammation, increased immunity, reduced cancer incidence, blocking tumor invasion and metastasis, and further clinical application as treatment with radiation and chemotherapy. These functions of selenium are mostly related to oxidation and reduction mechanisms of selenium metabolites. Hydrogen selenide from selenite, and methylselenol (MSeH) from Se-methylselenocyteine (MSeC) and methylseleninicacid (MSeA) are the most reactive metabolites produced reactive oxygen species (ROS); furthermore, these metabolites may involve in oxidizing sulfhydryl groups, including glutathione. Selenite also reacted with glutathione and produces hydrogen selenide via selenodiglutathione (SeDG), which induces cytotoxicity as cell apoptosis, ROS production, DNA damage, and adenosine-methionine methylation in the cellular nucleus. However, a more pronounced effect was shown in the subsequent treatment of sodium selenite with chemotherapy and radiation therapy. High doses of sodium selenite were effective to increase radiation therapy and chemotherapy, and further to reduce radiation side effects and drug resistance. In our study, advanced cancer patients can tolerate until 5000 µg of sodium selenite in combination with radiation and chemotherapy since the half-life of sodium selenite may be relatively short, and, further, selenium may accumulates more in cancer cells than that of normal cells, which may be toxic to the cancer cells. Further clinical studies of high amount sodium selenite are required to treat advanced cancer patients.

Placental Site Trophoblastic Tumors: Analysis of the Clinicopathologic Characteristics of 20 Cases in Korea.

OBJECTIVES: The aim of this study was to evaluate the clinicopathologic features of placental site trophoblastic tumors (PSTTs) in Korea. METHODS/MATERIALS: Twenty patients given a diagnosis of PSTT in Korea (1990-2013) were evaluated retrospectively, including 14 patients identified through a literature review and 6 patients identified through a medical chart review of a single institution. The analysis included patient age, antecedent pregnancies, time since antecedent pregnancy, presenting symptoms, serum ß-human chorionic gonadotropin level, International Federation of Gynecology and Obstetrics stage, treatment, outcome, and follow-up. RESULTS: The mean age of the 20 patients was 32 years (range, 25-53 years). The antecedent pregnancies included 8 term pregnancies, 8 abortions, and 2 molar pregnancies. The time since the antecedent pregnancy was less than 1 year in 16 patients (80%). Nineteen patients (95%) presented with abnormal vaginal spotting or amenorrhea. Serum ß-human chorionic gonadotropin levels ranged from normal to 13,480 mIU/mL, although most patients (80%) had a level less than 1000 mIU/mL. Seventeen patients (85%) presented with stage I disease. Ten patients (50%) underwent hysterectomy, and 14 patients (70%) were treated with chemotherapy with or without hysterectomy. In 11 evaluated patients, the median mitotic count index was 3.4 (0.4-10) per 10 high-power fields. The median follow-up time was 17 months (range, 1-68 months). There was no recurrence or death from disease. CONCLUSIONS: Korean patients with PSTT often have early-stage disease, which has a favorable prognosis even with fertility-preserving therapy. However, international studies are necessary to determine the optimal treatment and prognostic factors.

Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations.

OBJECTIVES: To investigate and analyze the BRCA mutations in Korean ovarian cancer patients with or without family history and to find founder mutations in this group. METHODS/MATERIALS: One hundred two patients who underwent a staging operation for pathologically proven epithelial cancer between January 2013 and December 2014 were enrolled. Thirty-two patients declined to analyze BRCA1/2 gene alterations after genetic counseling and pedigree analysis. Lymphocyte specimens from peripheral blood were assessed for BRCA1/2 by direct sequencing. RESULTS: BRCA genetic test results of 70 patients were available. Eighteen BRCA1/2 mutations and 17 unclassified variations (UVs) were found. Five of the BRCA1/2 mutations and 4 of the UVs were not reported in the Breast Cancer Information Core database. One BRCA2 UV (8665_8667delGGA) was strongly suspicious to be a deleterious mutation. BRCA1/2 mutations were identified in 11 (61.1%) of 18 patients with a family history and in 7 (13.5%) of 52 patients without a family history.Candidates for founder mutations in Korean ovarian cancer patients were assessed among 39 BRCA1/2 mutations from the present study and from literature reviews. The analysis showed that 1041_1043delAGCinsT (n = 4; 10.2%) and 3746insA (n = 4; 10.2%) were possible BRCA1 founder mutations. Only one of the BRCA2 mutations (5804_5807delTTAA) was repeated twice (n = 2; 5.1%). CONCLUSIONS: The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.

Photodynamic therapy for premalignant lesions of the vulva and vagina: A long-term follow-up study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate responses to photodynamic therapy (PDT) and its long-term efficacy in preserving normal anatomy and function in women with premalignant lesions of the lower genital tract. STUDY DESIGN/MATERIALS AND METHODS: Fifteen patients received PDT for vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), or vulvar Paget's disease between January 2003 and December 2013. Patients underwent colposcopy and/or vulvoscopy for assessment of lesions. Surface photoillumination with a 630-nm red laser light was applied to the lesions 48 hours after intravenous injection of 2 mg/kg photosensitizer (PSZ; Photogem®). The light dose to the lesions was 150 J/cm2 . RESULTS: The median age of the 15 patients (VIN II: 3, VIN III: 4, VAIN II: 2, VAIN III: 3, Paget's disease: 3) was 42.3 years. The complete response (CR) rate was 80% (12/15) at the 3-month follow-up and 71.4% (10/14) at the 1-year follow-up. There were two cases of persistent disease at the 3-month follow-up. One patient with persistent disease underwent partial vulvectomy three times for repetitive recurrence, and the other received secondary PDT with topical 5-aminolevulinic acid (5-ALA) and subsequently showed no evidence of disease (NED). Another patient achieved 90% remission through a combination of additional alternative treatments after showing partial response (PR). In two cases of CR, recurrence was observed at the 1-year follow-up. Regarding adverse events, photosensitivity reactions such as facial edema and urticaria occurred in 13.3% (2/15) and perineal pain occurred in one patient. CONCLUSIONS: PDT may be an effective alternative treatment for premalignant lesions of the female lower genital tract to preserve normal anatomy and sexual function without therapeutic impairment. Lasers Surg. Med. 47:566-570, 2015. © 2015 Wiley Periodicals, Inc.

Fertility preservation by photodynamic therapy combined with conization in young patients with early stage cervical cancer: a pilot study.

BACKGROUND: Vaginal radical trachelectomy (VRT) is the standard fertility preserving procedure for early stage cervical cancer patients. There have been reports in the literature, however, that VRT to be too radical procedure for early stage cervical cancer, as its post-operative obstetric morbidity was high. In this study, PDT with Loop electrosurgical excision procedure (LEEP) or conization was investigated as a less radical fertility preserving treatment alternative to VRT for early stage cervical cancer patients. METHODS: We analyzed data of 21 patients with early stage cervical cancer (stages IA-IIA) who underwent PDT with LEEP/conization from 2003 to 2012. LEEP or conization was performed before PDT in every case. For patients in stage IB1 or above, only those who were confirmed to be free of malignancy in frozen section by pelvic lymph node dissection received PDT. Surface photoillumination with red laser light at a wavelength of 630nm was applied to the cervix and the endocervical canal 48h after intravenous injection of 2mg/kg of photosensitizer. RESULTS: Median age of the 21 patients was 31 years old (range: 22-43), 19 patients (90.5%) of whom were nulliparous. Majority of the lesions were at stage IA1 (47.6%) or IB1 (42.9%). Histologically, 80.9% were squamous cell carcinoma. 5 patients (23.8%) had a lesion of 2cm or larger in diameter. There was one recurrence (4.7%) and no death during 52.6 months (6-114 months). Of the 13 women who attempted to get pregnant, 10 (76.9%) women conceived a total of 11 pregnancies. The first and second trimester miscarriages were 2 and 1 respectively, and 7 (70%) of the pregnancies reached the third trimester, of which 5 delivered at term. No tumor-related deaths or PDT-related severe adverse effects were noted. CONCLUSION: PDT combined with LEEP/conization could be an effective fertility sparing conservative treatment for young patients with early stage cervical cancer.

Porphyromonas gingivalis-induced autophagy suppresses cell proliferation through G1 arrest in oral cancer cells.

OBJECTIVES: We investigated the response of oral cancer cells to intracellular invasion of Porphyromonas gingivalis to define changes in the biological characteristics of oral cancer cells evoked by the presence of oral pathogenic bacteria within a tumour microenvironment. DESIGNS: The proliferative activity, cell cycle, and autophagic response were evaluated in oral cancer cells infected with P. gingivalis 381. ROS generation was detected in these cells by DCFDA assay, and its role in the responses of oral cancer cells to P. gingivalis infection was further investigated. RESUTLS: P. gingivalis inhibited proliferation of oral cancer cells by inducing G1 cell cycle arrest, but had no effect on apoptosis. Following infection with P. gingivalis, the expression of cyclin D1 and cdk4 was decreased in oral cancer cells, whereas p21, a Cdk inhibitor, was upregulated, in comparison with non-infected controls. Autophagy was prominently enhanced in these infected cells, presumably contributing to the suppressed proliferation. Further experiments revealed that such autophagic response was activated by the formation of reactive oxygen species, as evidenced by the lack of autophagic response and cell proliferation upon removal of reactive oxygen species. CONCLUSIONS: These findings provide a novel insight into the mechanism by which cancer cells are influenced by tumour microenvironment including oral bacteria.

Photodynamic therapy for management of cervical intraepithelial neoplasia II and III in young patients and obstetric outcomes.

OBJECTIVE: To evaluate the response and efficacy of photodynamic therapy (PDT) with or without loop electrosurgical excision procedure (LEEP)/conization (Cone) to preserve fertility in young patients with cervical intraepithelial neoplasia (CIN) II and III. METHODS: We reviewed the medical records of patients with CIN who had been treated by PDT. Among a total of 73 patients who received PDT for CIN II/III between September 2000 and August 2011, 59 patients aged 40 or younger and who wished to preserve fertility were included. Patients were divided into four groups: group (I) only PDT without LEEP (n = 13), group (II) PDT combined with LEEP/Cone (n = 15), group (III) PDT due to positive LEEP/Cone margin (n = 25), group (IV) PDT for recurrent CIN after LEEP/Cone (n = 6). Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine cervix and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. RESULTS: The median age of the 59 patients (CIN 2: 4, CIN 3: 22, carcinoma in situ: 31, adenocarcinoma in situ: 2) was 30.4 years. Twenty-two patients were unmarried and 38 were nulliparous. The complete remission (CR) rate was 98.1% (52/53) at 1 year follow-up except six patients followed up loss. The remaining one had recurred at 1 year after PDT, and one residual case at 3 months follow-up was regarded as CR showing NED after secondary PDT. Human papilloma virus (HPV) typing was performed. Before treatment HPV infection rate was 96.3% (52/54). HPV DNA could be no longer detected in 89.8% (44/49) and 87.0% (40/46) at 3 and 12 months after PDT. Among 29 patients who tried to be pregnant, 18 patients achieved 25 pregnancies (6 abortions, 1 ectopic, 1 preterm, 15 term, and 2 ongoing pregnancies.) There has been no fetal loss due to incompetent internal os of cervix. For adverse events, photosensitivity occurred in 13.6% (8/59) and cervical stenosis occurred in one patient. CONCLUSIONS: PDT combined with or without LEEP/Cone may be a potential alternative for effective conservative treatment of CIN in young patients who wish to preserve fertility.

Fertility preservation via photodynamic therapy in young patients with early-stage uterine endometrial cancer: a long-term follow-up study.

OBJECTIVE: We evaluated the effectiveness of photodynamic therapy (PDT) as a conservative fertility-sparing treatment in young women with early-stage endometrial cancer. METHODS: We reviewed the medical records of patients with endometrial cancer who had been treated with PDT. Of the patients with endometrioid adenocarcinoma, we included those younger than 35 years and in whom the lesion was confined to the endometrium. Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine endometrial cavity and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. Complete response was pathologically defined as the complete disappearance of adenocarcinoma or hyperplastic tissue. RESULTS: Sixteen patients were included in the study. Their mean age was 30.7 years, and the mean body mass index was 24.6 kg/m(2). The mean follow-up period was 78 months. Photodynamic therapy was used in 11 patients as primary treatment and in 5 patients as secondary treatment for recurrence after primary hormonal therapy. Complete remission was observed in 12 (75%) of the 16 patients. Of these 12 patients, 4 experienced recurrence (33%). Two of the 4 patients who experienced recurrence showed complete remission after the next course of PDT, and 1 of the 4 nonresponders also showed complete remission after the second course of PDT. The final response rate was therefore 68%. Of the 7 women who attempted to get pregnant, 4 had 7 successful pregnancies (57%, 4/7), resulting in 6 live births. No tumor-related deaths or PDT-related severe adverse effects were noted. CONCLUSIONS: Photodynamic therapy can be an effective conservative treatment method for fertility sparing in young patients with early-stage endometrial adenocarcinoma.

Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens.

Persistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile, and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS(3)) to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A(*)02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS(3) analysis of HLA-A(*)02 immunoprecipitates detected E7(11-19) peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E7(11-19) negative and lacked the HLA-A(*)02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A(*)02 alleles. Thus, the conserved E7(11-19) peptide is a dominant HLA-A(*)02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A(*)02:01 tumors lack expression of both E7(11-19) and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development.

Pregnancy and natural delivery following magnetic resonance imaging-guided focused ultrasound surgery of uterine myomas.

This report discusses a pregnancy case following a series of two consecutive magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) procedures for the treatment of two different myomas in an individual patient. Both procedures were completed without adverse events, and the patient conceived naturally four months after treatment. At 39 weeks, she gave birth to a healthy baby girl, via a vaginal delivery. There were no complications in the pregnancy or during labor.

Consolidation hyperthermic intraperitoneal chemotherapy using paclitaxel in patients with epithelial ovarian cancer.

BACKGROUND: We evaluated the efficacy and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) using paclitaxel as consolidation therapy in patients with epithelial ovarian cancer. METHODS: Between November 1999 and January 2004, 18 patients with a negative second-look and 1 patient with positive peritoneal cytology only with stage Ic-IIIc epithelial ovarian cancer received consolidation intra-operative HIPEC using paclitaxel. The HIPEC was performed with open-abdomen technique, using 6 L of lactated Ringer's solution containing paclitaxel 175 mg/m(2), for 90 min in hyperthermic phase (43-44 degrees C). The survival rates were compared with 24 patients treated with conventional therapy (control group). RESULTS: The 8-year progression-free survival rates were 63.16% in the HIPEC-paclitaxel group and 29.17% in the control group (P = 0.027). The 8-year overall survival rates were 84.21% in the HIPEC-paclitaxel group and 25.00% in the control group (P = 0.0004). The time interval between initial treatment and HIPEC was statistically significant with respect to progression-free and overall survival in the HIPEC-paclitaxel group. CONCLUSION: HIPEC with paclitaxel during 2nd-look laparotomy is feasible and relatively safe and showed a good effect on survival. In patients with epithelial ovarian cancer who have a complete pathologic response, HIPEC with paclitaxel should be considered as a consolidation treatment option.

Successful use of magnetic resonance-guided focused ultrasound surgery to relieve symptoms in a patient with symptomatic focal adenomyosis.

OBJECTIVE: To report a successful treatment of symptomatic adenomyosis using magnetic resonance-guided focused ultrasound surgery (MRgFUS). DESIGN: Case study. SETTING: General hospital. PATIENT(S): A 47-year-old premenopausal woman with focal symptomatic adenomyosis. INTERVENTION(S): MRgFUS. MAIN OUTCOME MEASURE(S): Score on the Uterine Fibroids Symptoms Quality of Life (UFS-QOL) questionnaire and the degree of menstrual pain. RESULT(S): Uterine Fibroids Symptoms reduced from 53 to 28 and the degree of menstrual pain reduced from 10 to 5. CONCLUSION(S): For adenomyosis patients who wish to preserve their uterus, MRgFUS may be a promising alternative to hysterectomy. Additional studies of the safety and efficacy of MRgFUS in this indication should be conducted.

Patient selection guidelines in MR-guided focused ultrasound surgery of uterine fibroids: a pictorial guide to relevant findings in screening pelvic MRI.

Uterine leiomyomas (fibroids), the most common benign tumor in women of childbearing age, can cause symptoms including dysmenorrhea, menorrhagia, urinary symptoms, pain and infertility. Hysterectomy is a common approach to treating uterine fibroids, and less invasive surgical approaches such as myomectomy and uterine artery embolization also have been shown to alleviate symptoms. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is the only totally non-invasive surgical approved method for treating uterine fibroids. In clinical trials, MRgFUS resulted in significant relief of uterine fibroid symptoms. The safe and effective use of MRgFUS is affected by fibroid type and location, position relative to adjacent anatomical structures and the presence of co-existent pelvic disease. Additionally, successful outcomes with MRgFUS have been correlated with the volume of fibroids ablated during the procedure. Thus, selection of patients in whom sufficient fibroid volumes can be treated safely using the MRgFUS system is critical for successful outcomes. The MR images in this pictorial essay provide examples of uterine fibroids for which MRgFUS should be considered and is designed to facilitate the selection of patients for whom MRgFUS is most likely to provide sustained symptom relief.

Differential expression of clusterin according to histological type of endometrial carcinoma.

OBJECTIVE: Clusterin expression has been associated with various malignancies. Endometrial carcinoma is divided into endometrioid and papillary serous type carcinoma according to the histological characteristics and regarding to the unopposed estrogenic stimulation. In this study, we investigated the expression profiles of clusterin according to the histological types and the effect of estrogen stimulation on its expression in endometrial carcinoma. METHOD: Clusterin expression in endometrial carcinoma tissues was examined by RT-PCR, Western blot analysis, and immunohistochemistry. 63 endometrioid and 10 papillary serous types of fresh cases and 81 endometrioid and 7 papillary serous types of paraffin-embedded cases were studied. Regulation of clusterin expression by beta-estradiol in HEC-1B and HEC-1A cells was investigated using RT-PCR and Western blot analysis. Cell proliferative function of clusterin was examined in 293T cells. RESULTS: We found higher expression of clusterin in endometrioid compared to papillary serous carcinoma using both immunohistochemistry (p=0.033) and Western blot analysis (p=0.024). The mRNA and protein expressions of clusterin in endometrioid carcinoma were higher than in benign endometrium (p=0.002). Forced expression of clusterin promoted 293T cell survival in a concentration-dependent manner, and estradiol treatment increased clusterin expression in HEC-1B but not in HEC-1A cells. CONCLUSIONS: These data suggest that clusterin expression is related to endometrioid carcinoma of endometrium, in which estrogen is involved in the regulatory network of clusterin.

Imup-1 and imup-2 overexpression in endometrial carcinoma in Korean and Japanese populations.

BACKGROUND: Endometrial carcinoma is a well known complex gynecological disorder. Our team suggests that this tumor is related to immortalization-up-regulated protein 1 and 2 (imup-1, imup-2), which are known to be involved in SV40-mediated immortalization. PATIENTS AND METHODS: RT-PCR and immunohistochemical staining were used to examine the mRNA expression levels and intracellular localization of imup-1 and imup-2 in endometrial carcinomas from Korean and Japanese patients. RESULTS: The imup-1 (4.1- and 23.6-fold) and imup-2 (4.8- and 2.7-fold) mRNA expression levels in endometrial carcinomas from both Korean and Japanese women were significantly higher than in normal endometrial tissues (p < 0.01). Strong expression of the IMUP-1 and IMUP-2 proteins were found in the tumor cytoplasm as well as in the nuclei. CONCLUSION: These findings demonstrate the up-regulation of imup-1 and imup-2 in human endometrial carcinomas and indicate that these molecules play a role in endometrial carcinogenesis in both Korean and Japanese patients.

Management of high-risk hydatidiform mole and persistent gestational trophoblastic neoplasia: the Korean experience.

OBJECTIVE: To test the efficacy of a new scoring system to differentiate high-risk hydatidiform mole (H-mole) and initiate early selective postmolar chemotherapy. STUDY DESIGN: According to Kim's scoring system, 262 patients were identified as high-risk H-mole patients. Fifty (19.1%) received early chemotherapy, and the rest constituted the control group. Salvage therapy with etoposide, methotrexate, actinomycin D/etoposide, cisplatin (EMA/EP) and taxol, cisplatin/taxol, etoposide (TP/TE) was applied in 21 cases of ultra-high-risk GTT. RESULTS: None of the 50 cases in the early chemotherapy group progressed to persistent GTT. However, 58.9% in the control group developed GTT with 8.0% drug resistance. Of those receiving salvage therapy in the 21 ultra-high-risk GTT cases resistant to EMA/CO, 10 of 14 (71%) receiving EMA/EP and 4 of 7 (57.1%) receiving TP/TE achieved remission. CONCLUSION: Early postmolar chemotherapy for high-risk H-mole is effective in preventing progression to persistent GTT and treatment failure. Ultra-high-risk GTT should be approached with multimodal treatment, including EMA/EP and TP/TE regimens.

Microsatellite instability in endometrioid type endometrial adenocarcinoma is associated with poor prognostic indicators.

Microsatellite instability (MSI) has been reported in 25% to 45% of sporadic endometrial carcinoma. The clinicopathologic and molecular characteristics of MSI-high phenotype in colorectal and gastric carcinomas have been widely investigated; however, the clinicopathologic impact of MSI on endometrial carcinomas remained unclear. This study was performed to determine the clinicopathologic and molecular significance of MSI in endometrial carcinomas. We analyzed the MSI status using National Cancer Institute-recommended 5 microsatellite markers, and the immunohistochemical profiles of various regulatory proteins of cell cycle and apoptosis using tissue microarray in 100 endometrial carcinomas. The results were compared between MSI-high and MSI(-) groups as for the traditional clinicopathologic prognostic parameters and the immunoreactivities of various regulatory proteins. We especially focused on the endometrioid type adenocarcinoma to exclude the bias from nonendometrioid type adenocarcinomas with more aggressiveness and a close association with MSI(-) phenotype. The incidence of MSI-high phenotype was significantly higher in endometrioid type than in nonendometrioid serous type (20% vs. 0%, P<0.001). It showed orderly increase in the frequencies of MSI-high phenotype in higher histologic grade (13% vs. 21% vs. 50% in histologic grade I, II, and III, P=0.039). The MSI-high phenotype was related with the presence of lymphovascular invasion (P=0.008), deep myometrial invasion (P=0.040), and the higher clinical stages (P=0.018) independent of tumor grade. We also found a correlation between MSI-high phenotype and higher cyclin A and skp2 immunoreactivity (P=0.03 and 0.05, respectively), known to be the poor prognostic molecular indicators. According to these results, the MSI may represent the poor prognostic impact on the endometrioid type endometrial adenocarcinoma.