Flowcytometry and immunhistochemistry for determination tumour heterogeneity in ovarian cancer

Das Ovarialkarzinom ist unter den bösartigen Genitaltumoren der Frau der dritthäufigste mit etwa 15 - 28 %, die Mortalität liegt mit 47 % jedoch deutlich höher. Die 5-Jahres-Überlebens-rate liegt bei nur 5-15 %. Charakteristisch für das Ovarialkarzinom ist seine biologische Heterogenität. In dieser Arbeit sollte die Häufigkeit einer intratumoralen DNA-Heterogenität beim Ovarialkarzinoms untersucht werden. Mittels flowzytometrischer Bestimmung der Ploidie und immunhistochemischer Analyse des Her2-Rezeptorstatus wurde außerdem der Einfluss einer Aneuploidie und / oder einer Her2-Überexpression auf die Gesamtüberlebenszeit bzw. das rezidivfreie Intervall untersucht. Es wurden retrospektiv insgesamt 81 Fälle epithelialer Ovarialkarzinome mittels Flowzytometrie (FCM) untersucht. Es konnten insgesamt 31 Fälle als diploid und 50 als aneuploid klassifiziert werden. In mehr als der Hälfte aller untersuchten Fälle zeigte sich eine intratumorale DNA-Heterogenität. Es konnte keine statistische Signifikanz zwischen Ploidie und Gesamtüberlebenszeit bzw. rezidivfreiem Intervall nachgewiesen werden. Bei 42 Patientinnen wurde außerdem eine Her2-Bestimmung durchgeführt. In 52,4 % der Fälle konnte eine vermehrte Her2-Überexpression nachgewiesen werden. In dieser Gruppe war das mediane rezidivfreie Intervall verkürzt im Vergleich zur Gruppe der Patientinnen, bei denen keine Her2-Überexpression gefunden wurde. Es zeigte sich jedoch nur ein geringfügiger Unterschied in der medianen Gesamtüberlebenszeit beider Gruppen. Ein statistisch signifikanter Unterschied war nicht nachzuweisen. Allerdings konnte insgesamt tendenziell ein ungünstigerer klinischer Verlauf der Erkrankung bei Patientinnen festgestellt werden, bei denen eine Her2-Überexpression nachgewiesen wurde. Die Bestimmung des Her2-Rezeptorstatus scheint somit eine sinnvolle Ergänzung zu den bereits etablierten Prognosefaktoren darzustellen.Ovarian cancer comes third in women malignant genital tumours, it is about 15 -28%, with 47% mortality is plain higher. The 5-year-survival-rate is about 5-15%. Characteristic for ovarian cancer is its heterogeneity. In this report the frequency of intratumorale DNA-heterogeneity in ovarian cancer was examined. By flowcytometry and immunhistochemical investigation of the her2-receptor the influence of aneuploidy and / or her2-overexpression at overall-survival or relapse-free time respectively was examined. Retrospectively a total number of 81 cases of epithelial ovarian cancer were investigated by flowcytometry (FCM). 31 of the 81 investigated cases were classified as diploid, 51 were classified as aneuploid. In more than half of the investigated cases intratumorale DNA-heterogeneity was found. There is no statistical significance between ploidy and overall-survival and relapse-free time respectively. Additionally in 42 patients there was carried out an examination of the her2-receptor status. In 52,4% of the cases an overexpression of the her2-receptor could be proved. In this group the median relaps-free time was shortened in contrast to the group of patients where no her2 overexpression was found. However there is only a small difference in median overall survival time between both groups. Statistically significant difference could not be proved. Though there is in conclusion a more unfavourable progress of the disease in patient where an overexpression of her2-receptor was found. Thus the examination of the her2-receptor status seems to be a useful complementary examination to the already established prognostic factors

Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase

OBJECTIVE: To analyze if oocytes can be obtained in all patients before cancer treatment within 2 weeks by initiating ovarian stimulation during the follicular or luteal phase. DESIGN: Prospective controlled multicenter trial. SETTING: Four university-based centers. PATIENT(S): Forty cancer patients before chemotherapy. INTERVENTION(S): Twenty-eight patients were stimulated with gonadotropins in the follicular phase (group I). In 12 patients (group II), ovarian stimulation was initiated in the luteal phase, and these received GnRH antagonists and recombinant FSH. In 14 patients, 143 oocytes were further processed for fertilization by intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Number of oocytes aspirated after ovarian stimulation, cumulative FSH/hMG dosage, viability and maturity of oocytes, and fertilization rate by ICSI. RESULT(S): Patients in group I (age 27.6 +/- 4.9 yrs) were stimulated on average for 10.6 days, and patients in group II (age 31.2 +/- 5.7 yrs) for 11.4 days. Total amount of FSH was on average 2,255 IU (I) and 2,720 IU (II) per patient. Average and median numbers of aspirated oocytes were, respectively, 13.1 and 11.5 (I) versus 10.0 and 8.5 (II); 83.7% (I) and 80.4% (II) of the oocytes were mature and viable and could be treated by ICSI. Fertilization rate was 61.0% (I) versus 75.6% (II). CONCLUSION(S): This pilot study suggests that oocytes can be obtained before cancer treatment efficiently irrespective of the phase of the menstrual cycle

Improving fertility preservation in cancer: ovarian tissue cryobanking followed by ovarian stimulation can be efficiently combined

This pilot study evaluated whether combination of partial removal of ovarian tissue for cryobanking followed by ovarian stimulation and cryopreservation of oocytes can improve the efficacy of fertility preservation without further delaying cancer treatment. Initial partial removal of ovarian tissue did not substantially affect the average number and quality of retrieved oocytes after ovarian stimulation in this study