Bone mineral density among Korean females aged 20-50 years: influence of age at menarche (The Korea National Health and Nutrition Examination Survey 2008-2011).

To evaluate a possible correlation between bone mineral density (BMD) and age at menarche, the present study used the BMD dataset of the Korea National Health and Nutrition Examination Survey IV-V (KNHANES IV-V). Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. INTRODUCTION: To investigate any correlation between bone mineral density (BMD) and age at menarche in Korean females using data from the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-V; 2008-2011). METHODS: In total, 37,753 individuals participated in health examination surveys between 2008 and 2011. A total of 5032 premenopausal females aged 20-50 years were eligible. Age, height, weight, and age at menarche were assessed. RESULTS: Results from the univariate linear regression and analysis of covariance (ANCOVA) indicated that age (per 1 year), height (per 1 cm), weight (per 1 kg), exercise (per 1 day/week), familial osteoporosis history (yes), parity (n = 0 to ≥4), and menarche age distribution were associated with BMD of the total femur, femur neck, and lumbar spine. After stratifying the bone area and adjusting for age, parity, alcohol intake, smoking, exercise, and familial osteoporosis history, no effect was seen for the total femur or femur neck. Age at menarche 16~17 and ≥18 years groups were associated with BMD of the lumbar spine only. CONCLUSIONS: Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. Females with late menarche may achieve lower peak bone mass at some skeletal sites, which may put them at greater risk for osteoporosis in later life.

Primary ovarian malignant mixed mesodermal tumor: report of four cases.

Malignant mixed mesodermal tumors (MMMTs) are highly aggressive and usually diagnosed at advanced stages. MMMT originates from either the ovary or the uterus. Because this disease is relatively rare, an optimal treatment modality has not yet been established. The authors report four cases of ovarian MMMT (one heterologous MMMT and three homologous MMMTs) during 1990-2011. The patients underwent operation immediately after histopathologically confirmation and were treated with platinum-based combination chemotherapy. The extent of operation, the outcomes of radiation therapy, and the proper chemotherapeutic regimen are still controversial. The authors report herein four cases of ovarian MMMTs alone with a brief literature review.

Aggressive angiomyxoma of the female genital tract: report of two cases.

Aggressive angiomyxoma (AA) was identified in 1983 and 250 cases of this rare tumor have since been reported in the literature. It is characterized by a locally infiltrative and recurrent nature; however, it rarely shows distant metastasis. Surgical managements can successfully treat AA patients but may result in a significant morbidity due to the large size and infiltration of the tumor. Less radical surgeries have recently been recommended in the treatment of this tumor, but adjuvant therapies have not yet been fully established. The authors report here two AA cases that were treated at their hospital, with a brief review of the literature.

Transection of the obturator nerve by an electrosurgical instrument and its immediate repair during laparoscopic pelvic lymphadenectomy: a case report.

Obturator nerve injury seldom occurs in gynecologic surgery. However, gynecologic oncologic surgery, including pelvic lymph node dissection, increases the risk of this type of injury. Microsurgical techniques are usually performed for the repair of the nerve injury. Herein the authors report a case of obturator nerve injury caused by an electrosurgical instrument during laparoscopic pelvic lymphadenectomy, and its prompt repair by laparoscopic procedure in a 44-year-old patient with cervical cancer.

Diagnostic value of CA125 as a predictor of recurrence in advanced ovarian cancer.

PURPOSE: The aim of this study was to establish the guidelines for detecting early recurrences of advanced epithelial ovarian cancer by use of the CA-125 level. MATERIALS AND METHODS: Eighty-five of the patients who met the inclusion criteria were enrolled in this study. The authors examined 25 incremental changes of CA125 from one to 25 IU/ml, and compared the CA-125 value with other prognostic factors. Increases in the CA-125 level from the nadir level were expressed as CA-125- increments. RESULTS: Among the 25 increments, a CA-125-8 (eight IU/ml) was selected as the predictor that was the most efficient and time-effective. CA-125-8 had a sensitivity of 91.5%, a specificity of 84.6%, a positive predictive value of 93.1%, a negative predictive value of 81.5%, an efficiency of 89.4%. and a median lead-time of 68.5 days (p <0.0001). CONCLUSION: The authors suggest the incremented CA-125-8 as a predictor of recurrent advanced ovarian cancer.

Association of KIR genes and HLA-C alleles with HPV-related uterine cervical disease in Korean women.

This study investigated whether killer-cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA)-C alleles, receptors and ligands of natural killer cells are associated with the development of human papillomavirus (HPV)-related cervical disease in Korean women. Blood samples from 132 women with HPV-related cervical disease and 159 women without HPV infection were collected for genotyping of KIR genes and HLA-C alleles. Although no relationship was found between KIR genes and HPV-related cervical disease, a significant relationship was found between HLA-C alleles as ligands of KIR and HPV-related cervical disease. Women with HPV-related cervical disease were found to be significantly more likely to carry HLA-C*0303, particularly those with HPV 16 or 18 infection, and less likely to carry HLA-C*01 compared to women without HPV infection. HLA-C*0303 was found to confer susceptibility to HPV-related cervical disease, whereas HLA-C*01 was found to confer a protective effect against HPV-related cervical disease.

A huge retroperitoneal liposarcoma: case report.

BACKGROUND: Soft tissue sarcomas are rare and account for less than 1% of all newly diagnosed malignancies. One-third of malignant tumors arising in the retroperitoneum are sarcomas. Liposarcoma is the most common soft tissue sarcoma and retroperitoneal sarcoma. Liposarcoma accounts for at least 20% of all sarcomas in adults and up to 41% of all retroperitoneal sarcomas. Here we present the case of a huge retroperitoneal liposarcoma and a brief literature review. CASE REPORT: A 34-year-old woman was referred to our hospital from a local clinic, because of abdominal distention, pain, and palpable mass. On admission we found that her abdomen was markedly distended. Computed tomography showed a the huge left ovarian mass that occupied almost the entire abdominal cavity. The mass consisted mainly of fat, and calcified material. She was operated under the diagnosis of a huge teratoma. The tumor was located in the retroperitoneal cavity and it abutted the left adnexa. The retroperitoneal tumor, including the left adnexa was removed. The tumor measured 22 x 15 x 11 cm, and showed many histological and pathological findings. On the basis of the histopathological finding, the tumor was diagnosed as a dedifferentiated liposarcoma of the retroperitoneum. The patient is presently undergoing radiation therapy. CONCLUSION: In retroperitoneal liposarcoma, histological subtype, incomplete resection, contiguous organ resection, and older age are strongly associated with tumor-related mortality. For liposarcoma, it is necessary to customize the treatment strategy on a case-by-case basis.

Parovarian tumors of borderline malignancy.

The incidence of a parovarian tumor is 10-20% of all uterine adnexal masses, however, it is benign in most cases, and a borderline or malignant tumor is extremely rare. The classification of disease stage and treatment is still controversial owing to its scarcity. We have managed one mucinous and two serous cystadenomas of borderline malignancy originating from paraovarian cysts in our institute over ten year. We report and discuss the cases herein.

A case of bilateral ovarian synchronous tumors (left ovarian serous papillary adenocarcinoma and right ovarian malignant mixed Müllerian tumor).

Synchronous bilateral ovarian cancer is extremely rare and there is no established guideline for management. A case of a 58-year-old multiparous woman with bilateral ovarian synchronous malignant tumors is presented. The clinical consideration and treatment of related cases are discussed.

Clinicopathologic analysis of extramammary Paget's disease.

PURPOSE: To retrospectively analyze the clinicopathologic characteristics of patients with extramammary Paget's disease who were surgically treated in a single institution. METHOD: The charts of 14 patients with extramammary Paget's disease were retrospectively reviewed, and the clinicopathologic data were collected and analyzed. RESULTS: From January 1990 to July 2009, 14 patients were treated at our institution. Most patients (11/14 patients) had delayed diagnosis. Two patients (14.3%) had associated malignant neoplasms. Eight of 14 patients (57.1%) had positive surgical margins; of these patients, five patients had no evidence of recurrence. In the six patients with negative surgical margins, two patients (33.3%) developed recurrence. CONCLUSIONS: The diagnosis of extramammary Paget's disease is commonly delayed. Because of the possible association with other malignancies before or after the diagnosis of extramammary Paget's disease, thorough examinations are recommended. Disease recurrence is common regardless of the surgical margin status, so long-term monitoring of patients is recommended.

Malignant mixed mullerian tumor of the cervix including components of a rhabdomyosarcoma: case report and literature review.

Malignant mixed mesodermal tumors (MMMTs) are composed of carcinomatous and sarcomatous components and have an aggressive metastatic potential, resulting in a poor prognosis. MMMTs of gynecologic origin typically arise from either the ovary or the uterus, and MMMTs of the cervix are extremely rare. Due to the rarity of MMMTs arising from the cervix, there is no consensus regarding treatment, prognosis, and outcome; however, aggressive surgical cytoreduction, combined with adjuvant platinum-based chemotherapy and/or radiotherapy, is recommended as the treatment of choice for MMMTs of the cervix. Cervical MMMTs are more often confined to the uterus at the time of diagnosis and frequently have non-glandular epithelial components. For these reasons, MMMTs of the cervix may have a better prognosis compared to the uterine counterparts. A case of an immunohistochemically confirmed primary MMMT of the cervix, including components of a rhabdomyosarcoma, is reported.

Development and characterization of human constitutive proteasome and immunoproteasome subunit-specific monoclonal antibodies.

Delta (Y), MB1 (X), and Z are the three catalytic beta-subunits located in the inner rings of the constitutive proteasome, an intracellular multicatalytic complex responsible for the generation of peptides presented by human leukocyte antigen (HLA) class I antigens to T cells. When cells are incubated with interferon-gamma, delta (Y), MB1 (X), and Z are replaced by LMP2, LMP7, and LMP10, respectively, leading to the expression of immunoproteasome which generates peptides with increased affinity for HLA class I antigens. The characterization of the expression of constitutive proteasome and immunoproteasome subunits in cells, normal tissues, and malignant lesions has been hampered by the lack or limited availability of constitutive proteasome and immunoproteasome subunit-specific monoclonal antibodies (mAbs), which are suitable for immunohistochemical staining. To overcome this limitation, we generated human delta (Y), MB1 (X), Z, LMP2, LMP7, and LMP10-specific mAb-secreting hybridomas from BALB/c mice immunized with peptides and recombinant fusion proteins. The mAbs SY-5, SJJ-3, NB-1, SY-1, HB-2, and TO-7 were shown to be specific for delta (Y), MB1 (X), Z, LMP2, LMP7, and LMP10, respectively, as they react specifically with the corresponding molecules when tested with a human B lymphoid LG2 cell lysate in Western blotting and with the peptide derived from each molecule in enzyme-linked immunosorbent assay. The reactivity of the six mAbs with the corresponding intracellular antigens resulted in intracellular staining when the mAbs were tested with microwave-treated and saponin-permeabilized cells in indirect immunofluorescence and with formalin-fixed, paraffin-embedded tissue sections in immunohistochemical reactions. These results suggest that the constitutive proteasome and immunoproteasome subunit-specific mAbs we have developed are useful probes to characterize the expression of proteasome subunits in normal tissues and in pathological lesions.

Elective vs. conservative management of ovarian tumors in pregnancy.

OBJECTIVES: To determine optimal management of the ovarian tumors in pregnancy. METHODS: This study included 89 cases of the ovarian tumor in pregnancy that required surgery at Holy Family hospital of the Catholic University from January, 1990 to December, 2001. Among 89 cases, 36 and 53 were emergency and elective surgery, respectively. Student's t-test and the chi(2)-test were used for statistical analysis and a P-value of <0.05 was considered statistically significant. RESULTS: The most common size of torsion of ovarian tumors during pregnancy was 6-10 cm and the incidence was the most frequent during the first trimester of pregnancy. The incidence of preterm delivery (<37 weeks) was higher in emergency surgery, but there was no difference in the gestational age at delivery, also no difference in the birth weight or the method of delivery. CONCLUSIONS: Although surgery for ovarian tumors in pregnancy is delayed until the onset of symptoms, adverse pregnancy outcome is not worsened when compared with that after elective surgery. We propose that conservative management would be used in optimal management of pregnant women with ovarian tumors.

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers.

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

Protein kinase C modulates telomerase activity in human cervical cancer cells.

Telomerase, a ribonucleoprotein reverse transcriptase that extends telomeres of eukaryotic chromosomes is repressed in normal somatic cells but is activated during development and neoplasia. The regulation mechanism of telomerase activity in cancer cells is not clearly known. In this report, a possible affect of PKC on telomerase activity was examined using HeLa and CUMC-6 cervical cancer cell lines. Exposure of cells to PKC inhibitor, bisindolylmaleimide I and Gö6976, and high levels of PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA) resulted in the inhibition of PKC activity in both cells. Telomerase activities were also inhibited by bisindolyl-maleimide I and Gö6976, respectively, in a time-dependent manner. As PKC activity changes in TPA-treated cervical cancer cells, telomerase activities were increased at low dose of TPA and decreased at high dose. The expression levels of human telomerase subunits, human telomerase RNA (hTR) were not influenced by PKC modulating drugs. In contrast, the expression of full-length human telomerase reverse transcriptase (hTERT) was decreased after exposure to bisindolylmaleimide I and Gö6976 in a time-dependent manner. hTERT expression was not affected by low dose of TPA. In contrast, high dose of TPA inhibited hTERT expression level. But the expression patterns of beta-deletion transcript of hTERT after 72 h of treatment with PKC inhibitors or high dose of TPA exposure were not discernable as compared with those of full-length hTERT transcripts to PKC modulating drugs. These results suggest that PKC-modulating drugs altered telomerase activities by affecting full-length hTERT expression profile in human cervical cancers.

AAC-11 overexpression induces invasion and protects cervical cancer cells from apoptosis.

To identify the genes involved in cervical carcinogenesis, we applied the mRNA differential display (DD) method to analyze normal cervical tissue, cervical cancer, metastatic lymph node, and cervical cancer cell line. We cloned a 491-bp cDNA fragment, CC231, which was present in metastatic tissue and cervical cancer cell line, but absent in normal cervical and cervical cancer tissues. The 491 bp cDNA fragment has 98% homology to the previously published sequence, AAC-11 (antiapoptosis clone 11). The levels of AAC-11 mRNA expressions in nine normal cervical and nine primary cervical cancer tissues were low. Its expression was higher in three metastatic tissues and five cervical cancer cell lines (HeLa, CaSki, SiHa, CUMC-3, and CUMC-6). Invasion of matrigel and adhesion to laminin by AAC-11 transfected CUMC-6 cells were increased by approximately 2-fold and 4-fold, respectively. Northern blot analysis showed that matrix metalloproteinase (MMP)-2 and membrane type 1 MMP (MT1-MMP) genes were found to be expressed in high levels in AAC-11-transfected cancer cells. But MMP-2 and MT1-MMP were not expressed in cells transfected with vector alone or wild-type cells. AAC-11-transfected cells expressed an elevated level of MMP-2 protein as assessed by immunoblotting. On the contrary, tissue inhibitor of MMP (TIMP-2) expression was detectable in cells transfected with vector alone or wild-type cells, respectively. Its expression was undetectable in AAC-11 transfected cells. In cervical cancer cells transfected with AAC-11, the expression of beta-catenin was up-regulated. These suggest that overexpressions of MMP-2 and MT1-MMP, loss of TIMP-2 expression, and up-regulation of beta-catenin by AAC-11 transfection may contribute to the development of cervical cancer invasion. AAC-11 gene transfection increased cervical cancer cell colonization. The effect of AAC-11 on cultured cervical cancer cells was associated with antiapoptotic process. Approximately 50% of the AAC-11 transfected cells in serum-free medium died after 2 weeks, compared to 1 week for vector alone or wild-type cells. These results suggest that AAC-11 may serve as a candidate metastasis-related and apoptosis-inhibiting gene in human cervical cancer.

Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human cervical cancers.

OBJECTIVE: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a classical glycolytic protein. A higher level of GAPDH mRNA was found in lung, pancreas, and prostate cancers, but in cervical carcinoma there have not been any reports about the level of GAPDH gene expression. So, we tried to investigate the GAPDH gene expression patterns in cervical carcinomas compared to normal cervical tissues, and the relationships between the expression levels of this gene and conventional clinicopathological parameters were evaluated. MATERIALS AND METHODS: In this study, 25 normal exocervical tissues, 35 primary untreated cervical cancer tissues, 2 cervical cancer cell lines, and 2 post-nude-mouse-derived cervical cancer cell lines were subjected to Northern blot analyses for GAPDH gene expression. RESULTS: Northern blot analyses revealed that the levels of GAPDH gene expression were elevated in 34 of 35 (97%) cervical carcinoma tissues and all of the 4 cervical cancer cell lines compared to normal cervical tissues. The levels of GAPDH gene expression were more prominent in rapidly proliferating cervical carcinoma cells. The levels of the GAPDH gene expressions in cervical cancer tissues were not associated with conventional clinicopathological parameters including clinical stage, histological type, and degree of differentiation. CONCLUSION: These results suggest that increased GAPDH gene expression is characteristic of human cervical carcinomas and that rapidly proliferating carcinoma cells express more enhanced GAPDH gene. Future gene therapy using antisense oligodeoxynucleotide directed against GAPDH mRNA might be another therapeutic tool for human uterine cervical carcinoma.