Granulosa cell tumors (GCTs) of the ovary account for 2 to 5 of ovarian malignancies. We present two patients with malignant ovarian adult GCT. In one patient, a combination of bleomycin, etoposide, and cisplatin was effective after initial surgery for malignant GCT. In the other, an aromatase inhibitor was effective for recurrent malignant GCT. We also review the literature for further management of this tumor. Because GCT of the ovary is rare, it will be necessary to elucidate the clinical phenotype and establish treatment protocols by accumulating and analyzing more patients.

Background

Early life-stage exposure to estrogen increases the risk of breast cancer. The objective of this study was to investigate the age at menarche and time to onset of regular menstrual cycles for Japanese women born between 1930 and 1985.

Methods

A cross-sectional study was designed using data from the baseline survey of the Japan Nurses’ Health Study. The data from 48,104 female nurses were analyzed. To view trends in age at menarche, the distribution of age at menarche was calculated for each birth year cohort. The distribution of time to onset of regular menstrual cycles was calculated for each birth year cohort. To estimate whether high-risk group of the estrogenic dependent disorders increase with succeeding generations, we defined the women who experienced menarche at ten years old or younger and started a regular cycle within one year as early age onset of ovulatory cycles.

Results

Average ages at menarche were as follows: 13.8 years for those born in the 1930s (n = 113), 13.3 years for the 1940s (n = 4,751), 12.8 years for the 1950s (n = 15,844), 12.3 years for the 1960s (n = 20,547), 12.2 years for the 1970s (n = 6,568), and 12.2 years for the 1980s (n = 281). The proportion of women who experienced the onset of regular menstrual cycles 1 year after menarche was 29.3% for those born in the 1930s, but decreased to 11.9% for the 1980s. On the other hand, the proportion of women who did not have regular menstrual cycles was 10.4% for those born in the 1930s, but rose to 19.8% in 1980s. The proportion of women who experienced menarche at 10 years old and started regular menstrual cycles within one year increased over time: the percentage was 0.0%, 0.4%, 0.6%, 1.1%, 1.3%, and 2.1% for the women born in 1930s, 1940s, 1950s, 1960s, 1970s, and 1980s, respectively.

Conclusions

The age at menarche of Japanese women born between 1930 and 1985 decreased, but the onset of regular menstrual cycling is delayed; so that the distribution of the start time of ovulatory cycles may have spread for younger generations. Those suggest that the high-risk group of estrogenic dependent diseases among Japanese women may increase in the near future.

Background

The present study investigated tumor proliferation in a tumor model using murine ovarian cancer cells with increased carbonyl reductase (CR) expression.

Methods

CR cDNA was transfected into murine T-Ag-MOSE ovarian cancer cells by lipofection. CR-transfected cells (CR induction group) or empty vector-treated cells (control group) were injected into the backs of 8-week-old nude mice at a concentration of 0.5 × 106 per 0.2 mL. Subsequent tumor proliferation in both groups was observed for 5 weeks.

Results

The control group showed an increase in tumor volume during the 5 weeks of observation. However, tumor volume in the CR induction group increased up to the second week but then decreased continuously until the fifth week of observation. The tumor growth curves for the two groups showed a significant difference (Mann-Whitney U test, P < 0.001). Histological and biochemical experiments were performed using tumor tissues isolated in the third week. Necrosis and inflammatory cell infiltration were noted for tumors in the CR induction group. Also, the number of apoptotic cells was significantly increased in the CR induction group compared with the control group (P < 0.001). Milk fat globule EGF factor 8, an “eat-me” signal for phagocytes such as macrophages, was expressed extensively in the tumor cytoplasm and interstitial cells of the CR induction group, and engulfment of apoptotic cells by macrophages was observed. Vascular endothelial growth factor expression in tumors was notably decreased in the CR induction group compared with the control group.

Conclusion

Increased necrosis due to engulfing of apoptotic cells by phagocytes attracted by increased milk fat globule EGF factor 8 was considered to be the mechanism of spontaneous tumor regression in the CR induction group.