Mutational Analysis of KRAS, BRAF, and TP53 Genes of Ovarian Serous Carcinomas in Korean Women

PURPOSE: To assess the prevalence of KRAS, BRAF, and TP53 mutations in cases of low-grade and high-grade serous carcinomas and to evaluate the clinical outcomes of these morphologically distinct carcinomas. MATERIALS AND METHODS: Patients with primary invasive serous carcinomas were classified according to the universal grading system. Grade 2 serous tumors were excluded. A total of 100 patients were included for clinical evaluation. Thirty-seven patients, including 20 with low-grade and 17 with high-grade carcinomas, were selected for mutational analysis. RESULTS: The low-grade carcinoma group was characterized by young age and premenopausal period compared with the high-grade carcinoma group, but there were no statistically significant differences in stage, metastasis of lymph node and residual disease. There were no statistically significant differences in survival rates, however, the low-grade carcinoma group showed a trend for improved progression-free survival compared with the high-grade carcinoma group of early stage (p = 0.064). Mutations in KRAS and BRAF were found in 6 (30%) and 2 (10%) patients in the low-grade carcinoma group, respectively, however, they were not found in the high-grade carcinoma group. KRAS and BRAF mutations were mutually exclusive, and both mutations were observed in 40% (8/20). The frequency of TP53 mutations in low-grade and high-grade carcinoma groups were found in 20% (4/20) and 70.6% (12/17), respectively (p = 0.009). CONCLUSION: Low-grade serous carcinoma shows mutation pattern different from that with high-grade carcinoma. As there were no significant differences in stage distribution and survival, especially in advanced stage, we suggest that more studies are needed to segregate these patients into distinct disease entities.

Comparative study of neoadjuvant chemotherapy before radical hysterectomy and radical surgery alone in stage IB2-IIA bulky cervical cancer / 부인종양

OBJECTIVE: To compare the efficacy of neoadjuvant chemotherapy with paclitaxel plus platinum followed by radical hysterectomy with radical surgery alone in patients with stage IB2-IIA bulky cervical cancer. METHODS: From November 1999 to September 2007, stage IB2-IIA cervical cancers with tumor diameter >4 cm, as measured by MRI, were managed with two cycles of preoperative paclitaxel and platinum. As a control group, we selected 35 patients treated with radical surgery alone. RESULTS: There were no significant between group differences in age, tumor size, FIGO stage, level of SCC Ag, histopathologic type and grade. Operating time, estimated blood loss, the number of lymph nodes yielded and the rate of complications were similar in the two groups. In surgical specimens, lymph-vascular space invasion (LVSI), nodal metastasis and parametrial involvement did not differ significantly between the two groups. In the neoadjuvant group, pathologic tumor size was significantly smaller and fewer patients had deep cervical invasion. Radiotherapy, alone and in the form of concurrent chemoradiation, was administered to more patients treated with radical surgery alone (82.9% vs. 52.9%, p=0.006). No recurrence was observed in patients who could avoid adjuvant radiotherapy owing to improved risk factors after neoadjuvant chemotherapy. There were no significant differences in 5-year disease free and overall survival. CONCLUSION: As neoadjuvant chemotherapy would improve pathologic prognostic factors, adjuvant radiotherapy can be avoided, without worsening the prognosis, in patients with locally advanced bulky cervical cancer. Neoadjuvant chemotherapy would be improving the quality of life after radical hysterectomy in patients with bulky cervical cancer.

Treatment efficacy of high dose progestin in young women with early stage of endometrial carcinoma / 대한산부인과학회지

OBJECTIVE: The aim of this study is to investigate the effectiveness of high dose progestins in young patients with early stage of endometrial cancer. METHODS: Between April 1998 and December 2005, 10 women with early stage of endometrial carcinoma were treated with high dose progestins as primary therapy for the purpose of saving fertility. RESULTS: They took 80~160 mg of megestrol acetate or 500~1,000 mg of medroxyprogesterone acetate per day, and then followed up with the endometrial curettages. Seven patients (70.0%) responded to the treatment. Three patients didn't respond and so underwent hysterectomy as definite treatment. Four patients were able to become pregnant after completing treatment. No patients died of their disease. CONCLUSION: The majority of patients with well-differentiated endometrial adenocarcinoma who underwent conservative treatment with a progestational agent responded to the treatment. High-dose progestin therapy can be used as primary therapy in selected young women with early stage of endometrial carcinoma.

Clinical Usefulness of Cytokeratin 7 and 20 Expression in Metastatic Ovarian Tumors / 대한산부인과학회지

OBJECTIVE: To investigate the pattern of Cytokeratin (CK) 7 and 20 expression and evaluate its clinical usefulness in the differential diagnosis of metastatic ovarian carcinoma. METHODS: One hundred eighty nine cases pathologically diagnosed as having metastatic ovarian carcinoma were reviewed from January 1990 to December 2003 at Asan Medical Center. Immunohistochemistry for CK7 and CK20 was performed in 92 cases. RESULTS: One hundred seventy five cases were originated from non-gynecologic organs. The most common primary site was stomach (88 patients) followed by colon (53 patients). Fourteen cases were originated from gynecologic organs, such as uterine cervix, endometrium, and fallopian tube. 82.5% (33/40) of the stomach cancers was CK7 positive, whereas only 23.5% (8/34) of the colorectal cancers was CK7 positive. 82.5% (33/40) of the stomach cancers and 100% (34/34) of the colorectal cancers was CK20 positive. CK7+/CK20+ pattern was the most frequent in stomach cancer (70.0%, 28/40). In colorectal cancer, CK7-/CK20+ pattern had the largest portion (76.5%, 26/34) and there was no CK7+/CK20- pattern in contrast to primary ovarian carcinoma. CONCLUSION: CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary and expression pattern of CK is one of the useful methods to differentiate primary ovary cancers from metastatic ovarian carcinomas from colon, especially in left side colon cancer.

Influence of Activin and Follistatin on Expression of Insulin-like Growth Factor (IGF)-I, II, Insulin-like Growth Factor Binding Protein (IGFBP)-1, 2, and 3 mRNA in Cultured Mouse Granulosa Cells / 대한산부인과학회잡지

OBJECTIVE: To investigate the influence of activin and follistatin on the expression of IGF (insulin-like growth factor)-I, II, IGFBP (insulin-like growth factor binding protein)-1, 2, and 3 mRNA in cultured mouse granulosa cells MATERIALS AND METHODS: The granulosa cells were obtained from the mouse and cultured for 6 days with 10 ng/ml of activin, 10 ng/ml of follistatin, and 10 ng/ml of activin with 10 ng/m of follistatin, respectively. The cells not treated with activin or follistatin served as control. Reverse transcription-polymerase chain reaction (RT-PCR) has been used to examine the expression of IGF-I, II, IGFBP-1, 2, and 3 mRNA. Results were analyzed with Kolmogorov-Smirnov test and analysis of variance (ANOVA) and statistical significance was defined as p<0.05. RESULTS: The expression of IGF-I and II mRNA were not different significantly. However, the expression of IGFBP-3 mRNA was significantly increased in the follistatin group compared to the control group (p<0.05) and significantly decreased in the activin with follistatin group compared to the control group (p<0.05). The expression of IGFBP-1 mRNA was seemed to be increased in the activin group and decreased in the follistatin group compared to the control group, respectively (p=0.07, p=0.07). The expression of IGFBP-2 and 3 mRNA were seemed to be decreased in the activin group compared to the control group (p=0.06, p=0.07, respectively). CONCLUSION: Activin and follistatin might play a role as regulators of mouse ovarian physiology by modulating the IGF system, especially IGFBPs.

A Case of Refractory Choriocarcinoma that Showed Complete Remission with Paclitaxel / 대한산부인과학회잡지

High-risk gestational choriocarcinoma in patients who have failed primary chemotherapy is known to have a very poor prognosis. About 25% of high-risk metastatic choriocarcinoma become refractory to EMACO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) and fail to achieve a complete remission. Currently, there is no standard salvage chemotherapeutic regimen for EMACO refractory choriocarcinoma. Paclitaxel, a taxane analog extracted from the bark of the western yew, has shown antitumor activity in a variety of cancers. However, there has been few case reports that described the effectiveness of paclitaxel to choriocarcinoma. We describe a 41-year old woman with refractory choriocarcinoma, who demonstrated dramatic response to paclitaxel treatment with a brief review of literature.