Proliferative activity in ectopic trophoblastic tissue.

Clinical observations have shown that tubal pregnancies develop individually different biological activities such as different growth rates, levels of beta human chorionic gonadotrophin (beta-HCG), or rates of tubal wall destruction. In the present study, we evaluated the proliferative activity of ectopic cytotrophoblastic tissue using immunocytochemistry with antibodies to Ki-67 (clone MIB-1). The rates of proliferation obtained were related to the maternal serum beta-HCG values. Reference data were obtained from placentas of intact intrauterine pregnancies (group I, n = 14). The proliferative activity of this tissue was compared to that of cytotrophoblastic tissue of tubal pregnancies (group II, n = 27). Ki-67-immunostained as well as non-stained cytotrophoblastic nuclei of the villi and the trophoblastic columns were counted separately, and results were expressed as percentage of positive cells. Serum beta-HCG values were determined twice, 48 h and immediately before operation. The cytotrophoblastic cells of intact intrauterine pregnancies (group I) showed uniform and high proliferative activities (80% on average in villi, 84% on average in columns). The average Ki-67 proliferation rate was significantly lower (P < 0.001) in trophoblastic tissue of tubal pregnancies (group II; 42% on average in villi, 61% on average in columns). Within the group of tubal pregnancies, higher intragroup differences were observed. The number of Ki-67-labelled cells was independent of the absolute preoperative serum beta-HCG values in both groups, yet they were clearly related to the relative increase of beta-HCG in maternal serum. At higher proliferation rates, there was a significant, growing increase of beta-HCG values (P < 0.01). We have found immunohistochemical evidence to support the previous clinical speculations that tubal pregnancies develop more heterogeneously and more slowly than intact intrauterine pregnancies. The development of the beta-HCG concentrations may be taken as an indirect parameter, reflecting proliferative activity of the trophoblast.