OBJECTIVE: To determine whether annual screening reduces ovarian cancer mortality in women with a family history of breast or ovarian cancer. METHODS: Data was obtained from the Prostate, Lung, Colorectal, and Ovarian cancer trial, a randomized multi-center trial conducted to determine if screening could reduce mortality in these cancers. The trial enrolled 78,216 women, randomized into either a screening arm with annual serum cancer antigen 125 and pelvic ultrasounds, or usual care arm. This study identified a subgroup that reported a first degree relative with breast or ovarian cancer. Analysis was performed to compare overall mortality and disease specific mortality in the screening versus usual care arm. In patients diagnosed with ovarian cancer, stage distribution, and survival were analyzed as a secondary endpoint. RESULTS: There was no significant difference in overall mortality or disease specific mortality between the two arms. Ovarian cancer was diagnosed in 48 patients in the screening arm and 44 patients in the usual care arm. Screened patients were more likely to be diagnosed at an earlier stage than usual care patients. Patients in the screening arm diagnosed with ovarian cancer experienced a significantly improved survival compared to patients in the usual care arm; relative risk 0.66 (95% CI, 0.47 to 0.93). CONCLUSION: Screening did not appear to decrease ovarian cancer mortality in participants with a family history of breast or ovarian cancer. Secondary endpoints, however, showed notable differences. Significantly fewer patients were diagnosed with advanced stage disease in the screening arm; and survival was significantly improved. Further investigation is warranted to assess screening efficacy in women at increased risk.
Aged ; Breast Neoplasms/*genetics ; *Early Detection of Cancer ; Female ; Humans ; Menopause ; Middle Aged ; Ovarian Neoplasms/diagnosis/*genetics

OBJECTIVE: To determine whether annual screening reduces ovarian cancer mortality in women with a family history of breast or ovarian cancer. METHODS: Data was obtained from the Prostate, Lung, Colorectal, and Ovarian cancer trial, a randomized multi-center trial conducted to determine if screening could reduce mortality in these cancers. The trial enrolled 78,216 women, randomized into either a screening arm with annual serum cancer antigen 125 and pelvic ultrasounds, or usual care arm. This study identified a subgroup that reported a first degree relative with breast or ovarian cancer. Analysis was performed to compare overall mortality and disease specific mortality in the screening versus usual care arm. In patients diagnosed with ovarian cancer, stage distribution, and survival were analyzed as a secondary endpoint. RESULTS: There was no significant difference in overall mortality or disease specific mortality between the two arms. Ovarian cancer was diagnosed in 48 patients in the screening arm and 44 patients in the usual care arm. Screened patients were more likely to be diagnosed at an earlier stage than usual care patients. Patients in the screening arm diagnosed with ovarian cancer experienced a significantly improved survival compared to patients in the usual care arm; relative risk 0.66 (95% CI, 0.47 to 0.93). CONCLUSION: Screening did not appear to decrease ovarian cancer mortality in participants with a family history of breast or ovarian cancer. Secondary endpoints, however, showed notable differences. Significantly fewer patients were diagnosed with advanced stage disease in the screening arm; and survival was significantly improved. Further investigation is warranted to assess screening efficacy in women at increased risk.
Aged ; Breast Neoplasms/*genetics ; *Early Detection of Cancer ; Female ; Humans ; Menopause ; Middle Aged ; Ovarian Neoplasms/diagnosis/*genetics

Adolescent ; Adult ; Biomarkers, Tumor ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; genetics ; pathology ; Octamer Transcription Factor-3 ; genetics ; Ovarian Neoplasms ; diagnosis ; genetics ; pathology ; Testicular Neoplasms ; diagnosis ; genetics ; pathology

OBJECTIVETo study the diagnostic value of HNF-1β and Napsin A for ovarian clear cell carcinomas, serous carcinomas, endometrioid adenocarcinomas and metastatic Krukenberg tumors.

METHODSImmunohistochemical EnVision method was used to detect the expression of HNF-1β and Napsin A in 38 cases of ovarian clear cell carcinoma, 30 cases of high-grade serous carcinoma, 22 cases of endometrioid adenocarcinoma and 16 cases of metastatic Krukenberg tumor. Expression of HNF-1β and Napsin A were compared, and sensitivity and specificity of clear cell carcinoma of the ovary were analysed.

RESULTSThe positive rate of HNF-1β in the ovarian clear cell carcinoma was 100%(38/38), higher than those in high-grade serous carcinoma and endometrioid adenocarcinoma (P<0.05), although significant difference was not observed from that of metastatic Krukenberg tumor (P>0.05). Napsin A expressed in 97.4% (37/38) of ovarian clear cell carcinoma, 6.7% (2/30) of high-grade serous carcinoma, 22.7% (5/22) of endometrioid adenocarcinoma. Napsin A expression in clear cell carcinoma was higher than those in high-grade serous carcinoma and endometrioid adenocarcinoma (P<0.01), and no expression of Napsin A was seen in metastatic Krukenberg tumor (P>0.05). The sensitivity and specificity of HNF-1β in the diagnosis of ovarian clear cell carcinoma were 100% and 52.9%, those of Napsin A were 97.4% and 91.2%, those of both HNF-1β and Napsin A were 97.4% and 91.2%, respectively. The sensitivity and specificity of HNF-1β or Napsin A in the diagnosis of ovarian clear cell carcinoma were 100% and 52.9%, respectively.

CONCLUSIONSHNF-1β is a more sensitive marker for the diagnosis of ovarian clear cell carcinoma, whereas Napsin A is a more specific marker. The combined detection of HNF-1β and Napsin A may be helpful for the diagnosis of clear cell carcinoma of the ovary.

Adenocarcinoma, Clear Cell ; diagnosis ; Aspartic Acid Endopeptidases ; genetics ; Biomarkers, Tumor ; genetics ; Carcinoma, Endometrioid ; diagnosis ; Cystadenocarcinoma, Serous ; diagnosis ; Female ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; Humans ; Immunohistochemistry ; Krukenberg Tumor ; diagnosis ; Ovarian Neoplasms ; diagnosis ; Sensitivity and Specificity

PURPOSE: Recent discovery of BRCA1 and BRCA2 genes has made it possible to perform presymptomatic diagnosis in hereditary breast/ovarian cancer families. We have previously reported germline mutations of the BRCA1 gene in Korean hereditary breast/ovarian cancer families. In that study two out of 13 families were found to have germline mutations in BRCA1 gene. One was a nonsense mutation in codon 1815, and the other was a frameshift mutation due to 2 base-pair deletion in codon 1701 of BRCA1 gene. This study was intended to identify germline mutations of the BRCA2 gene in Korean breast/ovarian cancer families. MATERIALS AND METHODS: Peripheral blood DNA was obtained from 10 breast cancer patients registered at the Korean Hereditary Tumor Registry with positive family history of breast and/or ovarian cancer. Exons 11 and 27 of the BRCA2 gene(together accounting for 50% of the coding region of the BRCA2 gene) were amplified by polymerase chain reaction(PCR) and screened for mutations by in vitro transcription/translation method. For confirmation of the mutations, automatic sequencing of the PCR products displaying abnormal truncated protein bands was perfomed. RESULT: We identified an abnormal truncated protein in the exon 11 of the BRCA2 gene from a member of hereditary breast cancer family, SNU-B4. Sequencing analysis revealed a 4 bp deletion in codons 1248-49 of the exon 11, resulting in frameshift that led to premature stop codon and truncation of the protein product. CONCLUSION: We have identified a germline mutation from a Korean hereditary breast cancer family. So far only one case of the same mutation has been registered in Database of BRCA2 mutation (BIC) by a commercial genetic diagnosis company, Myriad Genetics, Inc. Identification of the germline mutation in BRCA2 gene should aid in the accurate presymptomatic diagnosis of the at-risk members in this family.
Breast Neoplasms ; Breast* ; Clinical Coding ; Codon ; Codon, Nonsense ; Diagnosis ; DNA ; Exons ; Frameshift Mutation ; Genes, BRCA1 ; Genes, BRCA2* ; Genetics ; Germ-Line Mutation* ; Humans ; Ovarian Neoplasms* ; Polymerase Chain Reaction

Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we assessed the clinicopathological significance of key double-strand DNA break (DSB) repair genes, including BRCA1, BRCA2, BARD1, ATM, RAD51 and NBS1 in EOC cell lines and paraffin-embedded tissue sections from 140 EOC patients treated with cytoreductive surgery, followed by platinum-based chemotherapy. These samples were analyzed for the clinicopathological impact of DSB genes by western blot analysis, immunohistochemistry and quantitative real-time PCR. Of the DSB repair genes, BRCA1, ATM and NBS1, which are involved in the homologous recombination-mediated repair pathway, were related to aggressive parameters in EOC. When survival analysis was performed, NBS1 expression exhibited an association with EOC recurrence. Specifically, increased NBS1 expression was found in 107 out of 140 cases (76.0%) and correlated with advanced stage (P=0.001), high grade (P=0.001) and serous histology (P=0.008). The median recurrence-free survival in patients with positive and negative expression of NBS1 was 30 and 78 months, respectively (P=0.0068). In multivariate analysis, NBS1 was an independent prognostic factor for the recurrence of EOC. Together, these results suggest that NBS1 is a marker of poor prognosis for the recurrence of EOC and is associated with aggressive clinicopathological parameters.
Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Cell Cycle Proteins/analysis/*genetics ; Cell Line, Tumor ; *DNA Breaks, Double-Stranded ; *DNA Repair ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Glandular and Epithelial/diagnosis/*genetics/*pathology ; Nuclear Proteins/analysis/*genetics ; Ovarian Neoplasms/diagnosis/*genetics/*pathology ; Ovary/metabolism/*pathology ; Prognosis ; Real-Time Polymerase Chain Reaction ; Young Adult