Jacobus Pfisterer

Overrepresentation of 3q and 8q material and loss of 18q material are recurrent findings in advanced human ovarian cancer

In order to define the ability of comparative genomic hybridization (CGH) to detect and map genetic imbalances, we investigated 47 malignant ovarian tumors and 2 ovarian tumors of low malignant potential. The most common genetic changes in order of frequency included DNA gains of chromosome arms 8q (53%), 3q (51%), 20q (43%), 1p (32%), 19q (30%), 1q (28%), 12p (28%), 6p (21%), and 2q (19%). The smallest regions of overrepresentation could be defined in 3q26‐qter, 8q23‐qter, 1p35‐pter, 12p12, and 6p21‐22, respectively. Losses were detected on 18q (23%), chromosome 4 (23%), 13q (17%), and 16q (17%) with the smallest underrepresented regions on 18q22‐qter, 13q21, and 16q23‐qter. Also, losses of the X chromosome (19%) were detected, correlating with higher ages of the patients. Therefore, some of these X chromosome losses might be due to a well‐known aging phenomenon and in these cases will be more preferably lost during cell division and tumor progression. Our findings show that ovarian carcinomas reveal consistent chromosomal abnormalities. Further detailed studies of these regions with specific molecular genetic techniques may lead to the identification of oncogenes and/or tumor suppressor genes playing an important role in the tumorigenesis of ovarian carcinomas. Genes Chromosom Cancer 16:46–54 (1996).

Steroid receptors in ovarian carcinoma: Immunohistochemical determination may lead to new aspects

87 nonpretreated stage III/IV ovarian common epithelial carcinomas were studied for estrogen receptor (ER) and progesterone receptor (PR) content by both immunohistochemistry (IHC) and biochemical (DCC) analysis. While the DCC assay showed tumors to be receptor-positive in 62% (ER) and 66% (PR), receptor-positive malignant epithelial cells were only detected in 38% (ER) and 31% (PR) by IHC. There was only a low correlation between the semiquantitative results of ER and PR IHC and the corresponding values of DCC receptor determination. The finding of steroid receptor-positive stromal cells without any evidence of hormone receptor-positive epithelial tumor cells offers a possible explanation for discrepant results in numerous cases with obviously false positive results of DCC analysis. Since the considerable heterogeneity of steroid receptor expression present in many ovarian neoplasms can only be detected by IHC, it seems to be the appropriate method of ER and PR determination. Most patients were treated by both radical cytoreductive surgery (n = 76) and a platinum-based chemotherapy (n = 79). ER was not shown to be of significant prognostic value. However, survival was significantly better in patients with PR positive tumors (IHC and DCC) on univariate analysis. Residual tumor after primary surgery was the only remaining significant prognostic factor after multivariate analysis. Further studies are needed to clarify the biological function of steroid receptor-positive stromal cells in ovarian carcinomas.

Therapeutic strategies in cervical pregnancy

Cervical pregnancy is a rare condition associated with a high maternal morbidity rate. Standard recommendations for the management of this ectopic pregnancy are not available. This paper presents a case report and reviews the respective literature. In many cases hysterectomy was the ultimate solution. In order to avoid hysterectomy chemotherapy using methotrexate has been suggested. Local injections of prostaglandins or vasopressin have also been proposed. Based on data collected from the literature and our own experience it is concluded that the management of cervical pregnancy requires individualized therapeutic strategies to minimize the rate of hysterectomies.

CA-125 can be part of the tumour evaluation criteria in ovarian cancer trials: experience of the GCIG CALYPSO trial

Background:CA-125 as a tumour progression criterion in relapsing ovarian cancer (ROC) trials remains controversial. CALYPSO is a large randomised trial incorporating CA-125 (GCIG criteria) and symptomatic deterioration in addition to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (radiological) to determine progression.Methods:In all, 976 patients with platinum-sensitive ROC were randomised to carboplatin–paclitaxel (C-P) or carboplatin-pegylated liposomal doxorubicin (C-PLD). CT-scan and CA-125 were performed every 3 months until progression.Results:In all, 832 patients (85%) progressed, with 60% experiencing a first radiological progression, 10% symptomatic progression, and 28% CA-125 progression without evidence of radiological or symptomatic progression. The benefit of C-PLD vs C-P in progression-free survival was not influenced by type of first progression (hazard ratio 0.85 (95% confidence interval (CI): 0.66–1.10) and 0.84 (95% CI: 0.72–0.98) for CA-125 and RECIST, respectively). In patients with CA-125 first progression who subsequently progressed radiologically, a delay of 2.3 months was observed between the two progression types. After CA-125 first progression, median time to new treatment was 2.0 months. In all, 81%of the patients with CA-125 or radiological first progression and 60% with symptomatic first progression received subsequent treatment.Conclusion:CA-125 and radiological tests performed similarly in determining progression with C-PLD or C-P. Additional follow-up with CA-125 measurements was not associated with overtreatment.

Estrogen and progesterone receptors in ovarian neoplasms: discrepant results of immunohistochemical and biochemical methods

Ninety-five ovarian neoplasms were studied for ER and PR content by immunohistochemistry, and the results were compared to those of biochemical ER and PR determination in 89 cases. While there was no difference between the results of both methods of hormone receptor determination in the few non-epithelial tumors studied, there was only a low correlation between the semi-quantitative results of ER and PR immunohistochemistry, and the corresponding values of biochemical steroid receptor determination in 77 common epithelial carcinomas of the ovary. In a majority of cases with discordant results between both methods, tumors were hormone receptor positive by DCC analysis but negative by immunohistochemistry. The finding of ER or PR positive stromal cells without any evidence of hormone receptor positive epithelial tumor cells in such tumors offers a possible explanation for the apparent discrepancy. Ovarian carcinomas containing ER or PR positive epithelial tumor cells may constitute a smaller subgroup of all tumors thought to be hormone receptor positive when only results of biochemical methods of steroid receptor determination were available.

Phase II study of pirarubicin combined with cisplatin in recurrent ovarian cancer

Although 50%–80% of patients with advanced ovarian cancer demonstrate an objective response after platinum-based chemotherapy, a majority of these patients will ultimately experience a relapse of their disease. Effective second-line treatment for these patients is of the utmost importance. We performed a phase II study with cisplatin and pirarubicin (each drug 50 mg/m2 i.v. every 28 days) in 17 patients with relapsed or persistent ovarian carcinoma. All patients had received platinum-containing primary chemotherapy. Overall survival from the time of diagnosis was 38.3 months (45.3 months in relapsed ovarian carcinoma and 28.3 months in ovarian carcinoma persisting after primary chemotherapy). Survival from entrance into the study was 13.0 months (14.2 months in relapsed disease and 11.2 months in refractory disease). Time to progression was 10.3 months. An objective response was observed in 4 patients and another 3 patients had stable disease. Major toxicity consisted of emesis (grade III/IV in 60/64 courses) and myelosuppression WHO grade III/IV in 15 courses. Neurotoxicity occurred in 3 patients and nephrotoxicity in 1 patient. Alopecia occurred in 12 patients. Tachycardia and other low-grade heart toxicities were observed after 5 courses. Dose reduction was necessary because of severe myelosuppression in 4 courses and because of nephrotoxicity in 1 course. Delay of subsequent chemotherapy courses for more than 7 days was necessary after 13 courses and was always due to myelosuppression. The dose-limiting toxicity of combination chemotherapy with cisplatin and pirarubicin is myelosuppression. Response and survival rates are superior in patients with relapsed disease compared to patients with resistent ovarian carcinoma.

Co-cultivation of ovarian carcinoma cells with dermal fibroblasts induces fibroblast expression of sex steroid receptor transcripts and protein

We have previously reported that stromal fibroblasts of ovarian carcinoma specimens may express estrogen (ER) and progesterone receptors (PR) when the malignant epithelial cells do not, and even when the specimens have been obtained from such non-Müllerian structures as the omentum whose fibroblasts normally express neither ER nor PR. In an attempt to investigate whether our observations of the expression of ER and PR in fibroblasts surrounding metastatic invasive epithelial ovarian carcinoma cells might result from an interaction involving malignant epithelial cells and stromal fibroblasts, we co-cultivated in vitro BG1 ovarian carcinoma cells with sex steroid receptor-negative dermal fibroblasts to determine whether carcinoma cells might induce the latter to express ER or PR protein and transcripts at levels detectable by standard immunocytochemical (ICC) and in situ hybridization (ISH) techniques. We report the in vitro induction of ER and PR transcripts and protein in previously steroid receptor-negative skin fibroblasts after co-cultivation with BG1 ovarian adenocarcinoma cells. Such observations suggest that a juxtacrine mechanism is responsible for the observed phenomenon, possibly involving ER- and PR-inducing factors (ER-IF and PR-IF).