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The role of the neutrophil-to-lymphocyte ratio (NLR) in predicting sensitivity to chemotherapy and prognosis has attracted great interest in several types of cancer. In the present study, the correlation between pre-chemotherapy NLR and sensitivity to platinum-based chemotherapy and prognosis in patients with advanced serous ovarian carcinoma was examined by retrospectively reviewing the medical records of 50 patients with stage III-IV serous ovarian carcinoma from 2005 to 2012. Patients were divided into high-NLR (32 patients) and low-NLR (18 patients) groups according to a cutoff value of 2.47. This cutoff was calculated using a receiver operating characteristic (ROC) curve that demonstrated 84% specificity and 60% sensitivity. Patient characteristics, sensitivity to platinum-based chemotherapy and prognosis were subsequently compared. The results revealed no significant difference in patient characteristics between the two groups. In the low-NLR group, 14 of 18 patients (77.8%) were sensitive to platinum-based chemotherapy, whereas 11 of 32 were sensitive in the high-NLR group (34.4%) (P=0.007). Overall and disease-free survival (DFS) were significantly longer in the low-NLR than in the high-NLR group (P=0.013 and P=0.043, respectively). The current results suggested that pre-chemotherapeutical NLR may serve as a biomarker of sensitivity to platinum-based chemotherapy and prognosis in patients with advanced serous ovarian carcinoma.

We retrospectively investigated the characteristic magnetic resonance (MR) imaging findings of uterine neuroendocrine carcinoma (UNEC) compared to those of uterine malignant lymphoma (UML). Nine consecutive female patients with UNEC and 5 female patients with UML participated in this study. MR imaging features were evaluated retrospectively. On MR imaging, seven of 9 UNEC lesions and no UML lesions showed an exophytic growth pattern. All 9 UNEC lesions and no UML lesions showed a growth pattern along the surface of the endocervix or endometrium. Only 1 UNEC lesion and all 5 UML lesions showed diffuse enlargement of the uterus. No UNEC lesions and all 5 UML lesions showed a multinodular shape. These findings showed significant differences between lesions. Findings for margin, endophytic growth pattern, signal intensity, and homogeneity on T2-weighted and T1-weighted imaging did not differ significantly between lesion types. Apparent diffusion coefficient was significantly lower for UML lesions than for UNEC lesions, but was quite low for both types. Local invasion to surrounding tissues was more frequent in UML lesions than in UNEC lesions. There was no significant difference in the frequency of lymphadenopathy between two entities. UNEC lesions tended to show an exophytic growth pattern and growth along the surface of the endocervix or endometrium, even when diffuse enlargement of the uterus was present, while all UML lesions showed a multinodular shape and diffuse enlargement of the uterus without thickening of the cervical epithelium and endometrium.

Objectives CA125 is one of the most widely used tumor markers in gynecological cancer including endometrial cancer. Although CA125 expression in endometrial cancer has been investigated, its prognostic value remains controversial. In this study, we investigated diagnostic and prognostic applications of serum CA125 for endometrial cancer. Methods Between January 2006 and December 2012, serum CA125 levels were examined prospectively in 215 patients with endometrial cancer, and were then determined during treatment and at scheduled follow-up examinations in patients with elevated baseline serum CA125 levels. Results During this period, a total of 215 patients (stage I, 142; stage II, 19; stage III, 32; stage IV, 22) were treated for endometrial cancer. The median age was 60 years (28–85), and histology types included 191 endometrioid carcinoma and 24 others. Subsequently 52 patients (24.2%) relapsed at the time of the last follow-up and the median follow-up time was 91 months (1–143). Elevated serum CA125 levels were identified in 69 patients (32.1%) and were associated with relapse of disease (p=0.005). Among the 69 patients with elevated serum CA125 levels, 56 (81.2%) achieved remission and serum CA125 levels returned to the normal range in all cases. There is no statistically significant relationship between an elevated CA125 levels and OS (p=0.06). Conclusions Serum CA125 level seemed to be a potential prognostic indicator for endometrial cancer in clinical practice.

No potential tumour markers have been validated for prognosis in endometrial cancer. However, carcinoembryonic antigen (cea) is one of the most widely used tumour markers in various types of cancer. Although cea expression in endometrial cancer has been investigated, its prognostic value remains controversial, and no studies have investigated serum cea levels in large case series. In the present study, we investigated diagnostic and prognostic applications of serum cea for endometrial cancer. This prospective study was approved by our Institutional Review Board. Between January 2006 and December 2012, serum cea was measured prospectively in 215 patients with endometrial cancer and was subsequently measured during treatment and at scheduled follow-up examinations in patients with elevated baseline serum cea. During the study period, 215 patients (142 stage i, 19 stage ii, 32 stage iii, 22 stage iv) were treated for endometrial cancer. By the time of last follow-up, 52 had relapsed (24.2%), and the median follow-up duration was 45 months (range: 1&ndash, 95 months). Elevated serum cea was identified in 25 patients (11.6%) and was associated with histologic type (p = 0.04), histologic grade (p = 0.03), and myometrial invasion depth (p = 0.01). Elevated serum cea was not related to clinical stage, lymph node metastasis, distant metastasis, age, menopausal status, or body mass index. Relapse of disease was related to elevated serum cea (p = 0.006). Serum cea is a potential prognostic indicator for endometrial cancer.

Opportunities for patients undergoing hemodialysis to receive chemotherapy are increasing. A combination of paclitaxel and carboplatin (TC) is first-line chemotherapy in patients with Müllerian cancer. However, the optimal dose and time interval between the end of carboplatin administration and initiation of hemodialysis remains to be elucidated. TC was administered to a patient with fallopian tube cancer undergoing hemodialysis. The paclitaxel regimen was determined to be 135 mg/m2 (total of 210 mg) over 3 h. After paclitaxel administration, 125 mg of carboplatin was administered over 1 h to achieve a target area under the concentration-time curve (AUC) of 5.0 mg•min/ml using the Calvert formula. The time interval between the end of carboplatin administration and hemodialysis initiation was 1 h at the first cycle, 16 h at the second cycle and 20 h at the third cycle, and the AUC obtained was 2.86, 4.16 and 6.0 mg•min/ml, respectively. The desired AUC of free platinum was demonstrated and only mild side effects were observed at the third cycle. Therefore, hemodialysis was initiated 20 h after completion of carboplatin infusion at cycles 4–6. The total chemotherapy planned was completed without severe adverse events. Measurement of the concentration of free platinum subsequent to administration is useful for determination of the optimal dose of carboplatin and time interval following administration to obtain an adequate AUC. The present study suggests that carboplatin can be administered to a patient undergoing hemodialysis, and that an adequate interval between the end of carboplatin administration and hemodialysis initiation may be ~20 h.

Approximately 40% of all patients with ovarian cancer in Japan are aged ≥65 years. The aim of the present study was to evaluate the differences in prognosis and prognostic factors between elderly and younger patients with epithelial ovarian cancer. A total of 114 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-IV ovarian cancer who were initiated on primary treatment at the Osaka City University Hospital (Osaka, Japan) were included in this study. Patient characteristics, treatment outcome and prognosis were compared between elderly (aged ≥65 years) and younger patients, and the prognostic factors associated with overall survival were evaluated by univariate and multivariate analyses. The most common histological type in younger patients was clear cell carcinoma (33.8%) vs. serous carcinoma in elderly patients (44.1%), with a significant difference in the distribution of histological type (P=0.006). Complete resection was achieved in 56.2% of younger patients compared with 32.4% of elderly patients (P=0.03). The rates of standard primary treatment were comparable (56.7% of younger vs. 50.0% of elderly patients). Overall and disease-free survival did not differ significantly between the two groups. Multivariate analyses identified FIGO stage and standard primary therapy as prognostic factors in younger patients and performance status in elderly patients. Age was not an independent significant prognostic factor among patients with ovarian cancer. Therefore, performance status, rather than age, should be considered when selecting the optimal treatment for elderly patients based on objective assessment.

Minimal deviation adenocarcinoma (MDA), also known as adenoma malignum of the uterine cervix, accounts for only ~1% of uterine cervical adenocarcinomas. Adenoma malignum of the uterine cervix was initially described by Gusserow in 1870. Using magnetic resonance imaging (MRI), MDA appears as multilocular lesions with solid components that extend from the endocervical glands to the deep cervical stroma. Cytological evaluation and biopsies have low detection rates, therefore, it is difficult to diagnose MDA accurately prior to treatment. The current study describes a rare case of MDA that was difficult to differentiate from endometrial adenocarcinoma of the corpus uteri preoperatively, as the endometrial biopsy results suggested a well-differentiated endometrioid adenocarcinoma and MRI did not show typical images for MDA. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed under the diagnosis of endometrial cancer, and the mass was subsequently diagnosed as MDA of the uterine cervix by pathological examination of the hysterectomy specimen. Postoperatively, although two types of adjuvant chemotherapy were performed, the remaining tumor continued to grow, causing obstruction of the bilateral ureters and leading to bilateral hydronephrosis. The patient is currently alive with the disease 10 months following the surgery.

Sarcomas represent only 1% to 3% of vulvar malignancies. Leiomyosarcoma is a rare malignant tumor of the vulva; it can be mistaken for a benign tumor, which can lead to misdiagnosis and incorrect or delayed treatment. We report the case of a 51-year-old woman with leiomyosarcoma of the vulva. The patient presented to her primary gynecologist with a vulvar mass that she had first noticed 20 years prior. The tumor was suspected to be aggressive angiomyxoma, and biopsy of the mass and treatment with gonadotrophin-releasing hormone agonist (GnRHa) therapy were recommended. The patient declined treatment and opted instead for observation; however, the tumor grew rapidly in the following year and the patient was referred to our hospital. She underwent tumor resection, and pathology revealed leiomyosarcoma. The patient declined adjuvant chemo- and radiotherapy but has had no recurrence for 32 months.

Vaginal melanoma is a rare tumor, accounting for

Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24-84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1-12 days) and 3.4 days (range 1-9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (P

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a severe but treatment-responsive disorder, initially identified in young women with an ovarian teratoma. Symptoms include mood, behavior and personality irregularities that resemble acute psychosis. The present study reports the rare case of a patient with anti-NMDAR encephalitis and severe neurological symptoms, that exhibited a rapid recovery following a laparoscopic salpingo-oophorectomy. The 39-year-old woman was admitted to the Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine (Osaka, Japan) with a 5-day history of fever and stomach ache. One week later, the patient developed hallucinations and emotional lability. Initially, a diagnosis of limbic or herpes encephalitis was considered; thus, the patient was administered acyclovir and received steroid pulse therapy. However, the patient subsequently developed apnea, and in response, a tracheal intubation, mechanical ventilation and plasmapheresis were performed. Anti-NMDAR encephalitis was subsequently considered as a diagnosis and mediastinal and pelvic computed tomography (CT) examinations were conducted to detect for the presence of a teratoma. A 24×24-mm cystic lesion was identified in the pelvis from an abdominal CT scan and the lesion appeared to be an ovarian teratoma. In addition, serum and cerebrospinal fluid samples were collected, and were found to test positive for anti-NMDAR antibodies. A laparoscopic salpingo-oophorectomy was performed, which resulted in rapid improvement of the patients mental symptoms, followed by a complete recovery.

This study compared the DNA, RNA, and protein levels of osteopontin (OPN) in endometrioid endometrial cancer (EEC) and ovarian endometrioid cancer (OEC). In total, 63 cancer cases (EEC: 33, OEC: 30) were included. Of these, 47 (EEC: 26, OEC: 21) were examined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and 48 (EEC: 25, OEC: 23) were examined by quantitative PCR. OPN expression was detected in 15 (50.0%) of 30 EECs and in 14 (50.0%) of 28 OECs. There was no significant difference in the percentage of positive cytoplasmic OPN staining between the EECs and OECs (12.8 vs 10.4; p = 0.6811). The correlation between relative mRNA and protein expression levels was significant in both the EECs and OECs; however, the correlation between relative DNA and mRNA levels was not significant. There was no significant difference in OPN expression between the EECs and OECs.

The p16-cyclinD1/CDK4-pRb pathway (RB pathway) and p14ARF-MDM2-p53 pathway (p53 pathway) work at the G1-S checkpoint, and the ATM-chk2-CDC25-cyclinB1/cdk1 pathway works at the G2-M checkpoint. The disruption of these pathways is thought to be related to the prognosis of human cancer. In this study, we analyzed the status of these pathways in 107 epithelial ovarian cancer (EOC) patients by immunohistochemistry and evaluated the relationship of these results with chemotherapy response and the prognosis. Altered RB, p53, and G2 pathways were detected in 50.5% (54/107), 51.4% (55/107), and 33.6% (36/107) of cases, respectively. The overall survival (OS) of 77.3% for patients with a normal RB pathway was significantly higher than the OS of 50.0% for patients with an altered RB pathway (by Kaplan-Meier analysis, P = 0.0021). The OS of 66.2% for patients with a normal G2 pathway was significantly higher than the OS of 58.3% for patients with an altered G2 pathway (P = 0.0416). However, the status of the p53 pathway was not related to OS. By univariate and multivariate analyses, advanced stage, high histological grade, altered RB pathway, and altered G2 pathway were significant predictors of poor OS. However, there was no significant relationship between pathway status and chemotherapy response. The status of the RB pathway and of the G2 pathway were independent prognostic factors of EOC.

Objectives In tumorigenesis, loss of function of the G1 pathway (p16-CDK4/cyclinD1-pRB pathway (RB pathway) and p14-MDM2-p53 pathway (p53 pathway)) is a theoretically essential event. The simultaneous analysis of all components of the RB and p53 pathway may be able to explain cervical tumorigenesis. However, there are no reports in which all components of the G1 pathway and HPV typing were examined simultaneously in cervical cancer. Methods We examined HPV typing and the status of the G1 pathways simultaneously by PCR–SSCP, multiplex PCR, methylation-specific PCR, and immunohistochemical techniques in cervical neoplasia. A total of 105 samples (normal, 10; cervical intraepithelial neoplasm (CIN), 42; invasive cancer (IC), 53) were included. Results Abnormality of the RB pathway tended to be more frequent in ICs (60.4%) than in CINs (31.0%) (P = 0.069). The primary target was p16 (CIN, 14.3%; IC, 43.4%; P = 0.032). Abnormality of the p53 pathway was detected in ICs (56.6%) and in CINs (40.5%) (P = 0.1494). In particular, strong expression of MDM2 was higher in ICs (32.1%) than in CINs (7.1%) (P = 0.0045). Abnormalities of the RB and p53 pathways were higher in low-risk and negative HPV than in high-risk HPV (81.3% vs 51.4%, P = 0.0657; 81.3% vs 45.9%, P = 0.0328). Seven HPV-negative cases had abnormalities in the RB or p53 pathways. Conclusions In conclusion, abnormality of the G1 pathway may be one of the important mechanisms for carcinogenesis of low-risk and negative HPV cases.

Disruptions of the p16-CDK4/cyclin D1-pRb pathway (RB pathway) and the p14ARF-MDM2-p53 pathway (p53 pathway) are important mechanisms in the development of human malignancies. In this study, we investigated RB and p53 pathways in 46 epithelial ovarian cancers (EOCs). In the RB pathway, 16 (34.8%) of 46 cases had p16 gene alterations or loss of expression. The deletion of the p16 gene was a rare event. In 7 cases, we observed methylation in the 5`CpG island in the promoter region of the p16 gene. Abnormal expressions of pRb and CDK4/cyclin D1 were 10.9% and 30.4%, respectively. In the p53 pathway, 10 (21.7%) of 46 cases had p14ARF gene alterations or abnormal expression. In 4 cases, methylation in the 5`CpG island in the promoter region of the p14ARF gene was present. MDM2 overexpression was a rare event. Thirty-six (78.3%) of 46 patients had p53 gene alterations or expression. In our studied cases, p14ARF abnormalities were independent of p16 abnormalities. Abnormal RB and p53 pathways were present in 60.9% and 80.4% of cases, respectively. In conclusion, disruptions of p53 and RB pathways are frequent events and the inverse correlations were present between the abnormality of p16 and p14ARF in EOCs. H UM P ATHOL 32:988-996. Copyright © 2001 by W.B. Saunders Company

Purpose: Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease. Experimental Design: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance. Results: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemoresponse data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002). Conclusions: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.

Objectives. In this study, we analyzed the PTEN expression in a large collection of clear cell adenocarcinomas of the ovary. Furthermore, we analyzed the expression of cyclin D1 and p27, and investigated the correlation among all these variables. Methods. Totally, 40 clear cell adenocarcinomas were included in this study. The protein expression of PTEN, cyclin D1 and p27 was investigated by immunohistochemistry. Results. Of 40 clear cell adenocarcinomas, 15 (37.5%) lost all PTEN immunoreactivity. There was no significant correlation between PTEN expression and clinical stage. Cyclin D1 expression and loss of p27 expression were detected in 16/40 (40.0%) and 14/40 (35.0%) clear cell adenocarcinoma cases. There was no significant correlation between PTEN expression and cyclin D1 or p27 protein expression. Conclusions. Loss of PTEN expression is relatively common and both cyclin D1 and p27 expressions are not related with PTEN inactivation in clear cell adenocarcinoma of the ovary.

We examined human papillomavirus (HPV) typing and the status of ATM, chk2, CDC25C, cdc2 and cyclinB1 in cervical intraepithelial neoplasia (CIN) and invasive cancer (IC). A total of 93 samples [normal: 10; CIN: 34 (CINI:9, CINII:12, CINIII:13); IC: 49 (stage 1:10, stage II:21, stage III:15, stage IV:3)] were included in this study. HPV status was evaluated by the PCR non-radioactive HPV detection system. We analyzed ATM, chk2, CDC25C, cdc2 and cyclinB 1 protein expression by immunohistochemistry. HPV DNA was detected in 73.5% of 34 CINs and 89.8% of 49 ICs. Detection of HPV subtypes 16 and 18 was more frequent in ICs (46.9%) than in CINs (23.5%) (p=0.0387). Abnormal expression of ATM, chk2, CDC25C, cdc2 and cyclinB1 were 2.9%, 32.4%, 2.9% 20.6% and 0% in CINs and 8.2%, 30.6%, 10.2%, 46.9% and 12.2% in ICs. The alteration of cdc2 was higher in ICs than in CINs (p=0.0198). Altered expression of cdc2 was higher in HPV16 and 18 cases (69.6%) than in other cases (26.9%) (p=0.0042). However, the relationship between HPV typing and ATM, chk2, CDC25C and cyclinB1 expression was not significant. Cdc2 is implicated in cervical carcinogenesis and may be related to p53 inactivation by HPV.

The p16-cyclinD1/CDK4-pRb pathway (RB pathway) and p14ARF-MDM2-p53 pathway (p53 pathway) work at the G1-S checkpoint, and the ATM-chk2-CDC25-cyclinB1/cdk1 pathway works at the G2-M checkpoint. The disruption of these pathways is thought to be related to the prognosis of human cancer. In this study, we analyzed the status of these pathways in 107 epithelial ovarian cancer (EOC) patients by immunohistochemistry and evaluated the relationship of these results with chemotherapy response and the prognosis. Altered RB, p53, and G2 pathways were detected in 50.5% (54/107), 51.4% (55/107), and 33.6% (36/107) of cases, respectively. The overall survival (OS) of 77.3% for patients with a normal RB pathway was significantly higher than the OS of 50.0% for patients with an altered RB pathway (by Kaplan-Meier analysis, P = 0.0021). The OS of 66.2% for patients with a normal G2 pathway was significantly higher than the OS of 58.3% for patients with an altered G2 pathway (P = 0.0416). However, the status of the p53 pathway was not related to OS. By univariate and multivariate analyses, advanced stage, high histological grade, altered RB pathway, and altered G2 pathway were significant predictors of poor OS. However, there was no significant relationship between pathway status and chemotherapy response. The status of the RB pathway and of the G2 pathway were independent prognostic factors of EOC.

Objective: The purpose of this study is to compare DNA, mRNA and protein levels of the cyclin E between clear cell (CC) and serous (SC) ovarian carcinomas, and evaluate the relationship between cyclin E and p53 status. Method: We examined the DNA, mRNA and protein levels of cyclin E and the protein level of p53 in 44 CCs and 39 SCs using microdissected tissues. Results: Relative cyclin E mRNA expression was significantly higher in CC (3.62, 95% CI, 2.24–4.99) than in SC (1.75, 95% CI, 1.05–2.45; p = 0.0098). The percentage of positive nuclear staining of cyclin E was significantly higher in CC (48.3, 95% CI, 40.4–56.1) than SC (25.3, 95% CI, 17.4–33.3; p = 0.0001). The mRNA and protein expression of cyclin E was significantly correlated (r = 0.66, p < 0.0001). However, the correlation between relative DNA copy number and relative mRNA expression was not significant (r = –0.063; p = 0.66). Percentage of positive nuclear staining of cyclin E was significantly higher in p53 positive cases (51.8, 95% CI, 40.0–63.5) than p53 negative cases (36.2, 95% CI, 28.2–44.2; p = 0.028). Conclusions: Cyclin E expression is significantly higher in CC than in SC. Cyclin E expression is significantly related with p53 positivity.

Objectives: In this study, we examined the alteration of the G2 pathway in endometrial hyperplasia (EH) and endometrioid-type endometrial cancer (EC), and analyzed the relationship between the G2 pathway status and the p53 pathway status. Methods: A total of 103 cases (proliferative phase of the endometrium: 20, EH: 22, and endometrioid-type EC: 61 (I: 39, II: 5, III: 15, recurrence: 2)) were included in this study. We examined the ATM, chk2, CDC25C, cdc2, and cyclin B1 protein expression by immunohistochemistry. In 55 cases (EH: 15; EC: 40), we analyzed chk2 mutations by RT-PCR-SSCP. Results: There were no chk2 mutations in endometrial disease. Elevated or reduced expression rates of ATM, chk2, CDC25C, cdc2 and cyclin B1 were 4.5% (1/22), 0%, 0%, 0% and 4.5% (1/22) in EH and 3.3% (2/61), 4.9% (3/61), 13.1% (8/61), 9.8% (6/61) and 9.8% (6/61) in EC. Alteration of the G2 pathway was higher in EC (32.8%; 20/61) than in EH (9.1%; 2/22; p = 0.047). The G2 pathway was significantly higher in the altered p53 pathway group (48.4%; 15/31) than in the normal p53 pathway group (16.7%; 5/30) in EC (p = 0.0134). The altered p53 pathway tended to be related with the cdc2/cyclin B1 status (p = 0.0529). Conclusions: Alteration of the G2 pathway is thought to occur during carcinogenesis of the endometrium.

Objectives Chemotherapy-induced thrombocytopenia seemed to be a relevant problem in clinical practice. In this study, we investigated chemotherapy-induced thrombocytopenia recently performed in patients with gynecologic malignancy. Methods Between January 2009 and December 2011, we examined our reported chemotherapy-induced thrombocytopenia using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. We analyzed the incidence and clinical features of chemotherapy-induced thrombocytopenia (≧grade3: platelet count Results During this period we administered over 1614 infusions (29 regimens) to 291 patients with gynecologic malignancy. Median age was 60 years (24-84). Thrombocytopenia occurred in 43 (14.8%) patients over 56 (3.5%) chemotherapy cycles. Clinical bleeding occurred in 13 (4.5%) patients over 14 (0.9%) cycles. Major bleeding occurred in 7 (1.3%) cycles (gastrointestinal bleeding: 4, genital bleeding: 2, bladder bleeding: 1). Platelet transfusions were administered for 8 cycles. No life-threatening bleeding occurred in any patient. Thrombocytopenia was associated with more than five previous chemotherapy cycle (p = 0.03), previous radiotherapy (p = 0.0001), disseminated disease (p = 0.006), distant metastatic disease (p = 0.02) and poor performance status (p = 0.0001). Clinical bleeding was associated with previous radiotherapy (p = 0.003), distant metastatic disease (p = 0.03) and poor performance status (p = 0.02). Both clinical bleeding were not related with age, bone marrow metastases or platinum-based regimens. Febrile neutropenia was complicated with 35% of thrombocytopenia cycles and 43% of clinical bleeding cycles. Conclusions By estimating risk factor of clinical bleeding such as progression of disease and poor bone marrow reserve, safe management of chemotherapy-induced thrombocytopenia without unnecessary platelet transfusion may be possible in patients with gynecologic malignancy. Disclosure All authors have declared no conflicts of interest.

We analyzed the mechanism of estrogen receptor (ER) loss and status of the p53 pathway in 64 cases of endometrial cancer. 26.6% (17 of 64) of endometrial cancers lost ER. Methylation of the ER CpG island was significantly related to ER status ( P = 0.0074). However, the methylation site of the ER CpG island differed between breast and endometrial cancers. The abnormal expression rate of p14ARF, MDM2, p53, and the p53 pathway were 7.8% (5 of 64), 32.8% (21 of 64), 25.0% (16 of 64) and 53.1% (34 of 64), respectively. There was no significant difference in the overexpression of MDM2 between p53-positive cases (43.8%: 7 of 16) and p53-negative cases (29.2%; 14 of 48) ( P = 0.3595). Abnormal p53 was higher in grade 3 tumors (55.6%; 5 of 9) than in grade 1 and 2 tumors (20.0%; 11 of 55) ( P = 0.0364). The abnormality of the p53 pathway was higher in grade 3 tumors (88.9%; 8 of 9) than in grade 1 and 2 tumors (47.3%; 26 of 55) ( P = 0.0294). However, there was no significant difference in abnormal p53 pathway between ER-negative and ER-positive cases. In endometrial cancer, ER CpG island methylation was the important mechanism of ER loss. However, there was no significant relationship between the p53 pathway and ER status. HUM PATHOL 33:386-391. Copyright 2002, Elsevier Science (USA). All rights reserved.

Background: Chemotherapy-induced neutropenia seemed to be a serious problem in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia recently performed in patients with gynecologic malignancy. Methods: Between January 2009 and December 2011, we examined our reported chemotherapy-induced neutropenia using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. Results: During this period we administered over 1614 infusions (29 regimens) to 291 patients with gynecologic malignancy. Median age was 60 years (24-84). Neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. FN occurred after cycle 1 in 14 (56%) cycles. There were two neutropenic-related death cases. Neutropenia was associated with elderly age (over age 70) (p = 0.0001), less than five previous chemotherapy cycle (p = 0.02), disseminated disease (p = 0.03), platinum-based regimens (p = 0.0001), taxan-containing regimens (p = 0.0001) and combined therapy (p = 0.0001). Febrile neutropenia was associated with poor performance status (p = 0.0001), no previous chemotherapy (p = 0.05), disseminated disease (p = 0.0001) and distant metastatic disease (p = 0.03). Both neutropenia and febrile neutropenia were not related with bone marrow metastases or previous radiotherapy. Conclusions: Estimating risk factor of febrile neutropenia such as performance status and progression of disease seemed to be important for safe management of chemotherapy-induced neutropenia in patients with gynecologic malignancy.

There are no potential tumor markers validated for prognosis of endometrial cancer. However, sialyl Tn (STN) is a carbohydrate antigen that is associated with the production of mucin, which reportedly plays important roles in carcinogenesis. Although STN expression in endometrial cancer has been investigated, its prognostic value remains controversial and no studies have investigated serum STN levels in large case series. In this study, we investigated diagnostic and prognostic applications of serum STN for endometrial cancer. Between January 2006 and December 2012, serum STN levels were examined prospectively in patients with endometrial cancer. A total of 146 patients (stage I, 98; stage II, 15; stage III, 17; stage IV, 16) were treated for endometrial cancer. The median age was 60 years (28–83). Subsequently 29 patients (19.9%) relapsed at the time of the last follow-up and the median follow-up time was 44 months (1–83). Elevated serum STN levels were identified in 36 patients (24.7%) and were associated with histological grade (p = 0.02) and lymph node metastasis (p = 0.006). Elevated serum STN levels were not related to histological types, clinical stages, myometrial invasions, distant metastases, age, menopausal status, body mass index, or relapse. Among the 36 patients with elevated serum STN levels, 33 (91.7%) achieved remission and serum STN levels returned to the normal range. Seven patients (21.2%) with elevated serum STN levels at baseline relapsed and their serum STN levels were again elevated. Serum STN levels are a potential prognostic indicator for endometrial cancer.

Background Malignant melanoma is an extremely malignant tumor with an unpredictable profile of spread and variable periods of remission. The late recurrence of malignant melanoma after diagnosis and treatment is a rare but characteristic metastatic behavior of malignant melanoma. When the late recurrence of malignant melanoma occurs, the most common sites of metastasis are the skin, subcutaneous tissue and lymph nodes. Case A 41-year-old woman presented with recurrent malignant melanoma which had clinical features of an acute state mimicking peritoneal cancer. Seven years after the excision of the primary tumor, the patient noticed diffuse abdominal distention. The patient underwent computed tomography and magnetic resonance imaging examination, which demonstrated extensive nodularity of the peritoneal surfaces, soft tissue thickening of the omentum and large amount of ascites. Therefore, primary peritoneal cancer was initially considered the most likely diagnosis. The patient underwent an exploratory laparotomy. Macroscopically, a numerous number of white-yellow rubbery nodules of tumor were present diffusely in the ovaries and omentum and on the uterine serosal surface. The pathological examination showed poorly differentiated adenocarcinoma of peritoneum. The tumor cells showed strong positivity by immunohistochemistry for S-100, melan A and vimentin. The diagnosis was established post-operatively by immunohistochemistry. Our case was an unusual recurrent case of malignant melanoma occurring 7 years after diagnosis and treatment of malignant melanoma. Conclusion The incidence of malignant melanoma has been increasing. The late recurrence of malignant melanoma may be seen frequently in the future. A variety of imaging and pathological methods including an exploratory laparotomy may be necessary in cases of patients suspecting peritoneal cancer with a previous history of melanoma.

5045 Background: ABCF2 is a new member of the ATP-binding cassette transporter superfamily gene. We previously reported that ABCF2 protein is new biomarker in clear cell adenocarcinoma (CC) of the ovary and its expression may predict the response to chemotherapy and survival of CC patients (Proc ASCO 2005, Clin Cancer Res 2005). In this study, we examined ABCF2 expression in cervical cancer (CACX) and evaluated the relationship between ABCF2 expression and clinical factor. Methods: Formalin-fixed surgical samples from one hundred fourty CACX were included in this study. ABCF2 expression was investigated by immunohistochemistry. Positive expression of ABCF2 was >10% based on the cytoplasmic staining. Results: One hundred fourty patients were included in this study. The clinical stage was I in 86 patients, II in 38 patients, III in 10 patients, and IV in 6 patients. Histologic types were squamous cell carcinoma (SC) in 101 patients and non-squamous cell carcinoma (NSC) in 39 patients. The positive rate of ABCF2 in advanced stage (III + IV) was significantly higher than it in early stage (I + II) (p = 0.03). However, histologic type was not related with ABCF2 expression (SC 49.5% vs NSC 59.0%, p = 0.35). ABCF2-negative tumors had longer overall survival (OS) than ABCF2-positive tumors (p = 0.0014). The ABCF2 expression were correlated with further biological variables such as age, tumor stage, and histologic type for OS rate by univariate and multivariate Cox regression analysis. Multivariate analysis revealed that stage and ABCF2 were independent prognostic factor (Hazards ratio (HR) = 4.66, p = 0.0005; HR = 0.34, p = 0.025). Conclusions: The role of ABCF2 protein may predict the prognosis of CACX. [Table: see text] No significant financial relationships to disclose.

5172 Background: There is no standard chemotherapy regimen for R-OC and ER-OC. CPT-11 (a DNA topoisomerase I inhibitor) is active against OC. A combination of CPT-11 and DXR (a topoisomerase II inh...

5037 Background: Ovarian clear cell adenocarcinoma (CC) generally shows little response to combination chemotherapy and the overall prognosis is poor. However, the molecular pathobiology of CC rema...

5050 Background: Epithelial ovarian cancer (EOC) can be subdivided into five major histologic types (Serous(SC), Mucinous(MC), Endometrioid(EC), Clear cell(CC), Undifferentiated (UC)). Among them, ...

5013 Background: The biological behavior of EEC and EOC differs despite their histologic similarity. While EEC is usually diagnosed at an early stage and has a good prognosis, EOC is generally adva...