Identification of Target Genes in the Endometrial Carcinomas with Microsatellite Mutator Phenotype / 대한산부인과학회지

OBJECTIVE: Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability and microsatellite instability (MSI), exist in the endometrial carcinomas. Tumors with microsatellite mutator phenotype (MMP) are caused by defects in DNA mismatch repair genes. MMP tumors are believed to progress by accumulating frameshift mutations in coding microsatellite sequences of various cancer related genes including tumor suppressor genes, apoptosis related genes and DNA repair genes. Thus, the identification of the specific target genes in the MMP endometrial carcinomas is important for the elucidation of molecular pathogenesis of endometrial carcinomas. METHODS: We classified the MMP endometrial carcinomas and evaluated the frameshift mutations of the 11 genes containing coding microsatellite sequences by using 34 endometrial carcinomas and 4 MMP endometrial carcinoma cell lines. RESULTS: MSI was found in 6 of 34 endometrial carcinomas. In the endometrial carcinoma tissues, frequent mutations were found in TAF1B (68%), HT001 (50%), SLC23A1 (50%) and ACVR II (50%) in the MMP endometrial carcinoma tissues. The other 7 genes were infrequently mutated. Mutations of these target genes were more frequent in MMP endometrial carcinoma cell lines. CONCLUSION: we identified specific target genes in MMP endometrial carcinomas. These data demonstrate the mechanism of tumor progression in the MMP endometrial carcinomas.

Adjuvant therapy in cervical cancer patients with high risk factors

Neoadjuvant and adjuvant chemotherapies are used adjunctively with surgery or radiation and are among the treatment options that are now employed for reducing treatment failure in early-stage cervical cancers with high-risk prognostic factors. Adjuvant therapies have been reported to significantly improve survival than would otherwise be possible with surgery or radiotherapy alone. However, for advanced cervical cancers, sequential or concurrent chemo-radiotherapy does not appear to significantly increase survival. The combination of radiotherapy with IFN-a2a and RA in the treatment of patients with locally advanced cervical cancer showed high response rates, however this should be confirmed in larger studies. Recent reports show that postoperative adjuvant radiotherapy has no benefit in survival, but that postoperative adjuvant chemotherapy has improved survival. Toxicities and the optimum number of cycles of neoadjuvant and adjuvant chemotherapy, as well as biologic therapy, will follow along with individualized treatment based on high-risk prognostic factors. Although more comprehensive studies and longer follow up will be required for complete evaluation of these adjuvant therapies, preliminary results are promising.

Cell-mediated immunity in patients with invasive carcinoma of the cervix

Multiple in vitro immune parameters were investigated in thirty-four untreated patients with invasive carcinoma of the cervix and in twenty-five controls. The parameters measured were percentages and absolute counts of T and B cells, percentage of T cell subsets, lymphocyte response to phytohemagglutinin (PHA) and concanavalin A (Con A), natural killer (NK) activity, antibody-dependent cellular cytotoxicity (ADCC), and interleukin 2 (IL-2) activity. Patients with invasive cervical carcinoma, as compared with controls, showed a decrease in the percentage and count of T cells, a decrease in the percentage of helper-inducer (CD4+) T cells, decreased CD4+/CD8+ ratio, depressed lymphocyte response to PHA and Con A, and depressed NK and ADCC activities. There were no significant differences in these immune parameters between early and advanced tumor stages. The levels of total lymphocytes, monocytes, suppressor-effector (CD8+) T cells, and B cells were similar to those of the controls. IL-2 productivity in patients was lower than that in controls. In patients with invasive cervical carcinoma, a decrease in the percentage of CD4+ cells was associated with depressed PHA response and decreased IL-2 productivity was correlated with the reduced percentage of CD4+ cells and decreased NK activity. This study shows a significant defect in an important immune surveillance mechanism in patients with invasive carcinoma of the cervix and suggests that impaired IL-2 activity production may be related to quantitative and qualitative alterations in lymphocyte subpopulations which play a major role in immune surveillance against cervical cancer.

Flow Cytometric Analysis of DNA Content in Cervical Neoplasia Patients Infected with Human Papillomavirus Types 16 and 18 / 대한부인종양콜포스코피학회잡지

To investigate the role of human pepillomavirus(HPV) infection on DNA content of cervical cancers, thirty-seven cases af ceryical squamous carcinoma were studied with the method of flow cytometry for deoxyribonucleic acid(DMA) content and Southern blot hybridizalion for typing of HPV type 1.6 or type 18 DWA in cornbination with other elinical pnrameters. There were 18 dipleid cases(48.6%) and 19 aneuploid(51.4%). The mean age of the patients with diplaid and aneuploid tumars was 51.6 years and 53.6 years, respectively, No significant age difference was found between diploid and aneuploid groups. Six of 13(46.2%) carcinnma in eiiu and 13 of 24(54.2%) invasive cervical carcinoma were aneuploid, and t,he proportinn of aneuploid tumors was not significantly different between the two groups. Six of 10 tumors(60.0%) in stage I, 5 of 11 tumors(45.5%) in stage II, 2 of 3 tumors(66.7%) in stage III were aneuploid. The frequency was not significantly different according to the clinical stage, Aneuploidy was present in 50.0% of HPV 16 positive lesion, 66.7% of HPV 18 positive lesion, and 41.7% of HPV 16 and 18 negative lesion. There was no statistically difference in the incidenee of aneuploidy when all HPV lesions were compared. Of 25 patients with HFV 16 or l8 positive lesion, aneuploidy was demonstrated in the specimen of four of eight patients with careinoma in situ and nine of 17 with invasive cervical carcinoma. In suromary, we found thst the ineidere of DNA aneuploidy was somewhat higher when HPV 18 positive lesion was compared to HPV 16 and 18 negative lesion but the difference was not statistically significant.

Prognostic Significance of Human Papillomavirus Types 16 and 18 in Invasive Cervical Cancer / 대한부인종양콜포스코피학회잡지

Thirty-nine cases of invasive cervical cancer with human papillomavirus(HPV) DNA sequences were analyzed to detennine if HPV type 16 or 18 clinical or prognostic significance. HPV type was determined by Southern blotl hybridization. HPV 16 was detected in 12 cases, and HPV 18 in 5 cases. Sixty percent of HPV 18 tumors were grade III (3 of 5), whereas 8.3% (1 of 12) of HPV 16 tumors and 5.6% (1 of 18) of HPV 16/18 negative tumors were grade III. Age, clinieal stage, histologic cell type, lesion size, and liyrriph node metestasis in relation to HPV type were not statistically significant. The mean age of HPV 1~6 group was 50 years, compared to 47 years for the HPV 18 group. Of 30 squamous carcinomas, HPV 16 was detected in 12 cases(40.0%), and HPV 18 in 4 cases (13.3%). Of 4 adenosquamous and adenocarcinomas, HPV 16 was detected in 0 case(0.0%), and HPV 18 in 1 case(25.0%). Among stge IB-IIA caners, lymph node metastasis was associated with 20% of HP-V 16 cases(2 of 10) as cotinparxl with 25% of HPV 18 cases(1 of 4) and 7.7% Of HPV 16/18 negative cases (1 of 13). It is suggested that HPV type 18 might be associated with worse prognostic factos of invasive cervical cancer than HPV type 16.

Epithelial Ovarian Carcinoma: Analysis of Prognostic Factors

One hundred and two patients with epithelial ovarian carcinomas treated at Yonsei University College of Medicine from January 1966 through December 1985 were retrospectively reviewed. Stage and tumor grade were found to be highly significant prognostic factors. Other important prognostic factors included residual tumor volume and transcapsular extension. Age and the presence of ascites were prognostic factors of marginal importance. The present study proposes that accurate surgical staging is mandatory at initial surgery and that tumor grading should be included in the FlGO classification of epithelial ovarian cancers. Improved surgical management to reduce the residual tumor volume is important for advanced tumor stage. In early tumor stages, more effective treatment should be reserved for patients with transcapsular extension. Prospective investigation is necessary for further subset analysis.

Bladder dysfunction after radical abdominal hysterectomy

No abstract available.

Analysis of risk factors for postmolar trophoblastic disease: categorization of risk factors and effect of prophylactic chemotherapy

Early identification of high risk molar pregnancy is important in preventing the development of subsequent postmolar trophoblastic disease (PMTD). In the present study, evaluation of risk factors of developing PMTD, and indications for initiating prophylactic chemotherapy, and investigation of the effects of prophylactic chemotherapy were undertaken. One hundred and forty complete molar pregnancies treated at Yonsei University College of Medicine were retrospectively analyzed. Thirty-six cases of PMTD developed in these molar pregnancies during follow-up. Risk factors for PMTD were ranked according to frequency with which they were associated with PMTD. The patients with no risk factors were classified in the low-risk group, with one or two in the medium-risk group, and with three or more in the high-risk group. Prophylactic chemotherapy was administered to 14 of 52 low-risk, to 21 of 46 medium-risk, and to 17 of 42 high-risk patients. Among the high-risk patients, the time required for remission was significantly shorter in the group with prophylactic chemotherapy (13.5 weeks) than in the group without prophylactic chemotherapy (22.4 weeks). There were no differences in the duration until remission among the low- and medium-risk patients. Of the 52 patients who received prophylactic chemotherapy, 8 (15.4%) developed PMTD. Among the high-risk patients the occurrence of PMTD was significantly lower in the prophylactic chemotherapy group. Among the low-risk and medium-risk patients, there were no differences in the occurrence of PMTD between the chemoprophylaxis treated and untreated groups. Our results strongly support the use of prophylactic chemotherapy for patients that were designed under our high risk criteria. Prophylactic chemotherapy helps to prevent or reduce the risk of developing PMTD, and shorten the time required for complete remission in high-risk patients.

Interferon-alpha2a, 13-cis-retinoic Acid and Radiotherapy for Locally Advanced Squamous Carcinoma of the uterine Cervix: Preliminary Study / 대한부인종양콜포스코피학회잡지

Locally advanced cancer of the uterine cervix is a major cause of death worldwide. Standard treatment with rdiolherepy for locally advanced cancer of the uterine cnvix has a response rate of less than 50%. Resently concurrent chcmoradirothcrpay has been introduced but with some contvovesy. Interferon and retinoic acid are inducible proteins which posses many hiologic activities such as, antiproliferative, immunomodulatory and antineoplastic properties. Combination of interferon and retinoic acid has produced high response rates especially for patients with squamous cell carcinoma . And they may potentiate the radiation cytotoxicity as adiosensitizer. This study was underaken to assess the clinical efficacy of combination regimen with interferon-alpha2a, 13-cis-retinoic acid and radiotherapy from Dec. 1988 to Dex. 1994 at Severance hospital Yonsei uniersity. Twenty seven patients of locally advanced squamous cell carcionma of the uterine cervix enrolled in this study are evaluated for response and toxicity. The results were as follow: 1. Preliminary results of interferon-alpha2a 13-cis-retinoic acid and radiotherapy are 46.7% of response rate(33.3% complete response)and those of concurrent chemoradiotherapy are 41.7% of response rate(46.7% complete response). 2. Major toxicity of interferon-alpha2a, 13-cis-retinoic acid and radiotherapy is fever(60.0%), and only case of grade 2 anemia and one case of grade 1 AST/ALT elevation was noted. There was no grade 3 or 4 toxicity. Systemic interferon-alpha2a, 13-cis-retinoc acid and radiotherapy is highly active, well tolerated therapy for locally advanced cervical cancer.

Interferon-alpha2a, 13-cis-retinoic Acid and Radiotherapy for Locally Advanced Squamous Carcinoma of the uterine Cervix: Preliminary Study / 대한부인종양콜포스코피학회잡지

Locally advanced cancer of the uterine cervix is a major cause of death worldwide. Standard treatment with rdiolherepy for locally advanced cancer of the uterine cnvix has a response rate of less than 50%. Resently concurrent chcmoradirothcrpay has been introduced but with some contvovesy. Interferon and retinoic acid are inducible proteins which posses many hiologic activities such as, antiproliferative, immunomodulatory and antineoplastic properties. Combination of interferon and retinoic acid has produced high response rates especially for patients with squamous cell carcinoma . And they may potentiate the radiation cytotoxicity as adiosensitizer. This study was underaken to assess the clinical efficacy of combination regimen with interferon-alpha2a, 13-cis-retinoic acid and radiotherapy from Dec. 1988 to Dex. 1994 at Severance hospital Yonsei uniersity. Twenty seven patients of locally advanced squamous cell carcionma of the uterine cervix enrolled in this study are evaluated for response and toxicity. The results were as follow: 1. Preliminary results of interferon-alpha2a 13-cis-retinoic acid and radiotherapy are 46.7% of response rate(33.3% complete response)and those of concurrent chemoradiotherapy are 41.7% of response rate(46.7% complete response). 2. Major toxicity of interferon-alpha2a, 13-cis-retinoic acid and radiotherapy is fever(60.0%), and only case of grade 2 anemia and one case of grade 1 AST/ALT elevation was noted. There was no grade 3 or 4 toxicity. Systemic interferon-alpha2a, 13-cis-retinoc acid and radiotherapy is highly active, well tolerated therapy for locally advanced cervical cancer.

The analysis of risk factors influencing lymph node metastasis in invasive carcinoma of the cervix / 대한산부인과학회잡지

No abstract available.

Cell-mediated immune status in cervical carcinoma patients infected with human papillomavirus types 16 and 18 / 대한산부인과학회잡지

No abstract available.

Cervical stump cancer / 대한산부인과학회잡지

No abstract available.

Serum levels of circulating immune complexes in patients with cancer of uterine cervix / 대한산부인과학회잡지

No abstract available.

The effects of wild type p53 tumor suppressor gene expression on the normal human cervical epithelial cells or human epidermal keratinocytes transformed with human papillomavirus type 16 DNA

The inactivation of p53 and p105RB by viral proteins or by mutations plays a key role in the oncogenesis of cervical carcinoma. The E6 and E7 proteins of HPV type 16 can bind to p53 and p105RB tumor suppressor gene products, respectively. In the present study, we tested a simple in vivo model that could explain the interactions between HPV E6 oncoprotein and p53 tumor suppressor protein. Our results showed that the life span of normal cervical epithelial cells was increased up to 4.5 times when transfected with expression vector containing E6/E7 ORF of HPV type 16. However, these cells did not divide after second crisis. Therefore, we employed an established human epidermal keratinocytes, RHEK-1. When transfected with an expression vector containing E6 ORF of HPV type 16, RHEK-1 cells showed anchorage independent growth character. When RHEK-E6 cells were transfected with wild type p53 expression vector, the growth rate of the RHEK-E6 cells was diminished. After 48 hours of transfection, many cells showed apoptotic signal but no more apoptotic signal was observed thereafter. These results suggested that the overexpression of the wild type p53 could overcome the dysfunction of the p53 on the cell cycle regulation imposed by E6 protein although not being of physiological condition.

Clinical significance of second look laparotomy in ovarian cancer patients / 대한산부인과학회잡지

No abstract available.

Prognostic evaluation of regional lymph node morphology in uterine cervical cancer / 대한산부인과학회잡지

No abstract available.

Colposcopy Directed Cone Biopsy and Endocervical Curettage as Management of Carcinoma in Situ of the Uterine Cervix / 대한산부인과학회잡지

OBJECTIVE: The goal of this study was to evaluate the prognostic factors in relation with residual cervical intraepithelial neoplasia (CIN) in hysterectomized specimen of the patients diagnosed as carcinoma in situ of the uterine cervix (CIS) and underwent cone knife biopsies first. Also we investigated if colposcopically directed wide cone knife biopsy with endocervical curettage followed by electrocauterization could substitute for traditional hysterectomy as a conservative management of CIS. METHODS: Data were collected retrospectively from 169 patients who were diagnosed as CIS after colposcopy directed conization in Yonsei University Hospital from Jan 1997 to Dec 2001. The patients were divided into two groups, those who underwent colposcopically directed cone biopsy only (Group A) and those who received colposcopically directed cone biopsy and extrafascial abdominal hysterectomy (Group B). Pap smear, pelvic examination and punch biopsy of the uterine cervix according to symptoms and physical findings of the patients were performed for follow-up. Patient characteristics, histologic results and follow-up outcomes were compared using student t-test, x2 test, and logistic regression analysis. RESULTS: Among 169 patients, 82 (study group) received no further treatment while 87 (control group) were hysterectomized. 58 of control group showed residual CIN in colposcopically directed cone biopsy and 12 from these patients, residual CIN were found in hysterectomized specimen. Positive endocervical margin on conization was found as a significant predictor for residual disease after conization. Abnormal Pap smear results were reported in 10 patients of study group only, of whom 2 cases of CIN I, 8 cases cervicitis. CONCLUSION: The residual CIN in endocervical margin can predict whether hysterectomized specimen might contain residual CIN and no difference in life threatening prognosis existed between the patients received colposcopically directed cone biopsy only and hysteretomy, regardless of the residual CIN in cone biopsy margin. Based on these results, it is reasonable to choose expectant management over hysterectomy for treating CIS patients with marginal involvement.

Comparative Cytogenetic and Clinicopathologic Studies on Gestational Trophoblastic Neoplasia, especially Hydatidiform Mole

Hydatidiform mole has been known for its potential for malignant transformation and for its various chromosomal karyotypes. However, the relationship between histologic grading of hydatidiform mole and its future malignant transformation is still controversial. This study was undertaken to determine the cytogentic aspects of gestational trophoblastic neoplasia, especially of hydatidiform mole with respect to its malignant transformation. Cytogenetic studies were performed in 34 cases of hydatidiform mole, 2 cases of invasive mole, and 2 cases of choriocarcinoma. The results were analyzed comparatively using clinical histopathological and endocrinological (human chorionic gonadotropin titer) data. Among the 34 cases of hydatidiform mole studied, 26 cases were complete moles and the remaining 8 were partial moles with karyotypes being diploid (46, XX, 24, 46, XY, 2), and triploid (69, XXY) respectively. Two cases of XX mole among 26 complete hydatidiform moles developed distant metastasis during the follow-ups, suggesting transformation into choriocarcinoma; both cases showed 46, XX in karyotype and Grade III in histologic grading. Not one case of triploid partial hydatidiform mole transformed into malignancy. The karyotypes of the two cases each of invasive mole and choriocarcinoma were from neardiploid to hypotetraploid, and aneuploid cells were predominant in choriocarcinoma.

Two Cases of Surgical Intervention in Persistent Localized Choriocarcinoma / 대한산부인과학회잡지

Gestational trophoblastic tumors including choriocarcinoma bave become one of the most curable human malignancies with an overall cure rate exceeding 90%. Although systemic chemotherapy is the initial treatment for chorio- carcinoma, some patients with chemotherapy-resistant choriocarcinorna can be treated by integration of cbemotherapy, surgery and radio- therapy. We report two cases of persistent localized choriocarcinoma which was treated by surgical intervention.