BRCA1 germline mutations and polymorphisms in a clinic-based series of ovarian cancer cases: a Gynecologic Oncology Group study.

OBJECTIVE: The aims of this study were to determine the frequency of BRCA1 gene alterations in an unselected, clinic-based series of ovarian cancer cases; to evaluate the usefulness of family history in predicting the likelihood of a disease-causing mutation; and to document the occurrence of polymorphic variants in BRCA1 and to determine their distribution among families accordingly to history of breast and/or ovarian cancer. METHOD: Two hundred fifty-eight women with primary epithelial ovarian cancer, entered onto a nonclinical protocol of the Gynecologic Oncology Group, were analyzed for BRCA1 germline alterations by single-strand conformation polymorphism analysis. RESULTS: Protein-truncating mutations in BRCA1 were identified in 12 patients (4.6%). The median age of cancer diagnosis in BRCA1 mutation carriers was 47 years compared to 57 years in patients without mutations (P = 0.02). All but 1 of the patients with BRCA1 mutations reported a family history of breast and/or ovarian cancer and 8 had a first-degree relative with cancer. Twelve mutations of unknown significance were also identified. An association was also noted between the presence of common polymorphisms in BRCA1 and family history of cancer. Polymorphisms were present at higher frequency among women without a family history of cancer compared to women with positive family histories, suggesting they are associated with reduced risk. CONCLUSION: In a clinic-based series of ovarian cancer patients, germline BRCA1 mutations were detected in 12 of 258 (4.6%) patients. A strong correlation was noted between the presence of mutations and family history of breast and/or ovarian cancer, indicating that these women are most likely to benefit from genetic susceptibility testing.

BRCA1-related and sporadic ovarian cancer in the same family: implications for genetic testing.

OBJECTIVE: The aim of this study was to present a family with both BRCA1-related and sporadic ovarian cancer and address current difficulties in genetic testing. METHODS: BRCA1 mutation detection was performed on a family having four confirmed cases of ovarian cancer, two cases of breast cancer, and one case each of colon, stomach, and prostate cancer. The incidence and types of cancer were consistent with a BRCA1 mutation although previous linkage analysis had excluded this family as being due to BRCA1. RESULTS: A protein-truncating mutation in BRCA1, denoted 2799delAA, was identified in the germline DNA of each of the women affected with breast and ovarian cancer in this family except the proband, who was diagnosed with ovarian cancer at age 65. CONCLUSIONS: In an earlier study, which sought to determine the proportion of site-specific ovarian cancer due to BRCA1, the family described in this report was wrongly identified as not being due to BRCA1 when, in fact, all but one of the breast and ovarian cancer cases carry a deleterious BRCA1 mutation. Our analysis suggests that the proband, who was the first of the women in this family to seek genetic counseling, developed ovarian cancer by chance and not as the result of an inherited mutation. We describe the results of our analysis in light of current issues that face clinicians who may be involved in genetic testing for breast and ovarian cancer predisposition.

Ovarian steroid cell tumors, not otherwise specified: a case report and literature review.

Steroid cell tumors, not otherwise specified, are rare ovarian sex cord-stromal tumors with malignant potential. The majority of these tumors produce steroids with testosterone being the most common. A case of a 46-year-old woman who presented with sudden onset of virilization and a pelvic mass is reported. Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed.

Evaluating sex chromosome content of sorted human sperm samples with use of dual-color fluorescence in situ hybridization.

OBJECTIVE: Although most methods for selecting the sex of offspring by sorting spermatozoa are ineffective at shifting the ratio of Y- to X-containing cells, some commercial sources continue to offer such services. Our objective was to evaluate commercially "sorted" samples with use of dual-color fluorescence in situ hybridization and to identify variations in assessment by comparing motile and total sperm populations, donors, observers, and fluorescence in situ hybridization probes. STUDY DESIGN: Cryopreserved sperm from seven anonymous donors were processed as for insemination. Sperm cells from each total sample or motile subfraction were prepared for fluorescence in situ hybridization by incubation with disulfide-reducing agents to expand sperm nuclei. Two sets of X and Y chromosome-specific, fluorophore-labeled deoxyribonucleic acid probes were used. At least 400 nuclei from each preparation were classified independently by three blinded observers. Hybridization efficiency, aneuploidy, and sex chromosome content were evaluated in subsets of five unsorted, five female-oriented, and five male-oriented samples. Total and motile subfractions were compared with eight samples. Fluorescence in situ hybridization probes were compared in five paired unsorted samples. RESULTS: No differences were detected between washed samples and paired motile subfractions. No differences in hybridization and aneuploidy were detected between groups of sorted samples. The Y/X ratio was significantly different between the sorted groups. However, male-oriented samples had a lower Y/X ratio than female-oriented samples did. Observer and probe choice accounted for small but significant variations that did not alter conclusions about the X/Y ratio for sorted samples. CONCLUSION: In a series of 10 sorted samples from one commercial source, dual-color fluorescence in situ hybridization demonstrated a small but significant shift in the sex chromosome ratios among samples. However, this shift was opposite to that expected by the orientation of the sorted samples.

Laparoscopy during pregnancy. A survey of laparoendoscopic surgeons.

OBJECTIVE: The purpose of this study was to survey the Society of Laparoendoscopic Surgeons (SLS) for their experience with laparoscopy during pregnancy and to develop a database on the safety and complications of laparoscopy in pregnancy. STUDY DESIGN: A survey questionnaire was mailed to 16,329 laparoscopic surgeons from the SLS mailing database. Seven questions were asked: number of laparoscopic procedures in pregnancy, type of operation, gestational age, intraoperative and postoperative complications, insufflation agent and insufflation pressure. Only surgeons who had performed laparoscopic procedures in pregnancy were asked to return surveys. RESULTS: One hundred ninety-two (1.2%) surveys were returned. Complete information was available on 413 laparoscopic cases. There were five intraoperative complications, including inadvertent placement of a Veress needle into a pregnant uterus. There were 10 postoperative complications. CONCLUSION: This is the first report to specifically address the safety and complications of laparoscopy in pregnancy. This study suggests that laparoscopy may be safe during pregnancy; however, it was limited by the biases of surveys and retrospective studies.

Erythema nodosum associated with streptococcal infection in pregnancy.

BACKGROUND: Erythema nodosum (EN) is a condition characterized by the presence of painful erythematous nodules on the pretibial aspects of the lower extremities. EN is thought to be a local inflammatory, immune-mediated reaction to a number of systemic antigenic stimuli. This condition is noted most often in women between menarche and menopause and is associated with certain drugs, infections, and pregnancy. However, no reports in the literature describe EN as a result of streptococcal infection during pregnancy. CASE: A 21-year-old, white woman, G(3)P(0020), presented at 13 weeks gestation with a 2-week history of erythematous, tender lesions on the pretibial aspects of both legs consistent with EN. The patient reported having had a "flu-like" illness at the same time the lesions developed. The "flu" symptoms resolved within 10 days without medical intervention, but the lesions on her legs persisted. An initial antistreptolysin-O (ASO) titer was elevated at 960 Todd units (normal values: preschool and adults <85; school-age and young adults <170). Six days later, she presented to the emergency department with complaints consistent with a urinary-tract infection. She was empirically treated with a 10-day course of amoxicillin, 500 mg t.i.d. Although the patient was treated with amoxicillin for a presumed urinary-tract infection (which was culture-negative), the lesions resolved after her completion of the antibiotics. Twelve weeks later, a repeat ASO was within normal limits. The EN lesions did not recur. CONCLUSION: Although many etiologic factors are identified as causes of EN, the condition is usually self-limiting, requiring only minimal supportive measures until it resolves. A careful history should be obtained and a physical examination performed to exclude other causes. If a recent streptococcal infection is identified or presumed, a 10- to 14-day course of antibiotics is warranted.