Radioimmunodetection of cervical carcinoma xenografts with (111)In-labeled MAb Cx-99 detected by a hand-held gamma detector.

PURPOSE: To establish a radioimmunodetection (RAID) system for localization of cervical cancer by labeling 111-indium ((111)In) to a monoclonal antibody against cytokeratin 19 (MAb Cx-99), and detecting it with a hand-held gamma detector in an animal model. METHODS: MAb Cx-99 was labeled with 111-Indium by the DTPA chelating method. From the second day to the seventh day after injection of this immunoconjugate into athymic nude mice bearing cervical cancer cell line CC7T xenografts, the biodistribution ratios of tumor and non-tumor radioactivity were detected by a hand-held gamma detector. Data were also correlated with the data detected by the conventional gamma counter. RESULTS: The labeling efficiency of this (111)In-labeled MAb Cx-99 and (111)In-labeled MOPC was 91.6% and 95.5%, respectively. After injection, the liver, kidney and lung were initially noticed to have high radioactivity, but the localization of tumor/tissue ratios increased progressively as time passed, indicating the effect of delayed detection for distinguishing tumor from non-tumor tissues. Except for the spleen, the range of tumor/tissue ratios was 1.18-32.7 and 1.14-39.35 for the fourth day and the seventh day, respectively. The tumor/spleen ratio remained low until the seventh day after injection, thus indicating that the spleen might have a different excretion rate. CONCLUSION: This study indicated the feasibility of a hand-held detection system in the localization of cervical cancer after injection of (111)In-labeled MAb Cx-99. The effect of delayed detection was obvious by the decreasing high bindings in the liver, spleen and kidney, with the applicable detection time being four to seven days after injection.

Frequent gain of copy number on the long arm of chromosome 3 in human cervical adenocarcinoma.

We analyzed genomic aberrations in 20 cervical adenocarcinomas by comparative genomic hybridization (CGH). Most tissue samples (85%) showed DNA copy number changes; gains were more common than losses. The most consistent region of chromosomal gain was mapped to chromosome arm 3q, found in 70% of the cases, with a minimal common region of 3q28-ter. Other recurrent amplifications of genetic material were detected on 17q (45%), 1p (30%), 1q (25%), and 11q (20%). High-level copy number increases were found in chromosomal regions 3q27-ter and 9pter-13. DNA losses were seldom observed, occurring primarily in underrepresented regions of chromosome arms 4q, 13q, and 18q. The presence of high-risk human papilloma virus genomes in the cervical adenocarcinoma samples was detected in 90% of the cases. However, there was no correlation between human papilloma virus type and the pattern of genomic changes. This study is the first report of CGH analysis in human cervical adenocarcinoma. Among the major genomic alterations, our results demonstrate the importance of DNA copy increases of chromosome arm 3q in the development of cervical adenocarcinoma and identify other amplified chromosomal regions that are also associated with cervical carcinogenesis.

BRCA1 mutations in Taiwanese with epithelial ovarian carcinoma and sporadic primary serous peritoneal carcinoma.

BACKGROUND: Germline BRCA1 mutations of sporadic ovarian cancers are presumed to be rare events, except among specific populations. To date, the status of germline BRCA1 mutations in Taiwanese with primary epithelial ovarian carcinoma (PEOC) is still unknown. In this study, we tried to answer part of this question. METHODS: Sixty-four patients documented with PEOC, four patients with family history of breast and/or ovary cancer syndrome and five patients with sporadic primary serous peritoneal carcinoma (PSPC) were enrolled in this retrospective study from January 1994 through June 1999. At the same time, 50 normal healthy Taiwanese without family history were enrolled in this study. Germline DNA from these patients was screened for mutations in the BRCA1 gene using polymerase chain reaction-based single-stranded conformation polymorphism analysis (PCR-SSCP). Shifting DNA bands were sequenced. RESULTS: One of the 64 patients with PEOC (1.6%) exhibited germline BRCA1 heterozygous mutation which was exon11 single-base substitution at nucleotide1047 (CAG to TAG). One of the five patients with PSPC (20%) exhibited an exon11 single-base substitution at nucleotide 914 (TCT to TCC) with resultant silent mutation. One of the normal healthy Taiwanese (2%) was found to have an exon 2 single-base substitution at nucleotide 152 (A-->C) which was also a silent mutation. No mutations of BRCA1 were detected in four patients with a family history of breast and/or ovarian cancer. CONCLUSIONS: Based on this study, it was very difficult to obtain precise data to prove the value of applying genetic testing of BRCA1 mutations in Taiwanese patients with sporadic epithelial ovarian cancers or sporadic PSPC and even with a family history of breast and/or ovarian cancer because of its rare event and because of the too small number of cases available in this study.

Optimal debulking surgery is an independent prognostic factor in patients with FIGO IIIC primary epithelial ovarian carcinoma.

BACKGROUND: Ovarian cancer is a well-known disease with a poor prognosis. Due to the relatively small number of cases in Taiwan, the outcome and prognostic factors of patients with primary epithelial ovarian carcinoma are unknown. METHODS: We retrospectively studied patients with proven surgical and pathologic (Federation Internationale de Gynecologie et d'Obstetrique) FIGO IIIC primary epithelial ovarian carcinoma. All patients underwent standard staging surgery, including washing cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, retroperitoneal lymphadenectomy, infracolic omentectomy and excisional biopsy of all suspicious lesions followed by adjuvant chemotherapy with four to 12 courses of cyclophosphamide, epirubicin and cisplatin (CEP) or cyclophosphamide, adriamycin and cisplatin (CAP) intravenously, every three weeks. To avoid the coeffects of chemotherapy and surgical procedures upon the outcome, patients who received paclitaxel-based regimens or underwent incomplete surgery were excluded. Ninety-eight patients from 1990 to 1996 were identified. RESULTS: The mean follow-up time was 28.7 months, ranging from 5.4 months to 105.9 months. The cumulative five-year disease-free survival rate for all patients was 31.6%. Optimal debulking surgery was completed in 41.8% of patients, which contributed to long-term patient survival (54% vs 16%, p < 0.0001), compared to patients without optimal debulking surgery. Optimal debulking surgery was the only statistically significant independent prognostic factor for five-year disease-free survival using multivariate analysis. CONCLUSIONS: To improve survival of patients with FIGO stage IIIC epithelial ovarian carcinoma, optimal debulking surgery should be performed as the initial form of surgical intervention.