Masafumi Koshiyama

Immunohistochemical analysis of distribution of estrogen receptors and progesterone receptors in the postmenopausal endometrium

Objective. To examine the expression of sex steroid receptors (ER: estrogen receptor; PR: progesterone receptor) in the postmenopausal endometrium (PMEM) and the relationship to clinical data for studying its characters.

Expression of multidrug resistance-associated protein in endometrial carcinomas: correlation with clinicopathology and prognosis.

The objective of the study reported here was to investigate the expression of multidrug resistance-associated protein (MRP) in endometrial carcinomas and to evaluate the relationship between its expression and clinical data. Using immunohistochemistry, we examined MRP expression in 15 normal endometria, 10 cases of endometrial hyperplasia, and 64 cases of endometrial carcinoma. The normal endometrial glands were weakly immunopositive throughout the menstrual cycle. In addition, we found a progressive increase in the MRP expression of the endometrial hyperplasias. Of the 64 cases of endometrial carcinoma, 62 (97%) expressed MRP. Of these 62 cases, 34 (55%) showed strong immunostaining (>/=50%) and 28 (45%) showed weak immunostaining (<50%). In particular, the intensity of the immunostaining was very strong in 25 (71%) of the 35 grade 1 carcinomas. There was a significant difference in MRP expression between the grade 1 carcinomas and the more poorly differentiated carcinomas (grade 2 or grade 3) (P <.01), especially at stages 1a and 1b (P <.001). However, beyond stage 1c, there was no significant difference in MRP immunoreactivity between the histologic differentiations. Furthermore, beyond stage 1c, those patients with strongly MRP-positive carcinomas had a relatively poorer survival rate than those with weakly MRP-positive carcinomas (P <.05). We concluded that MRP immunoreactivity was already present in normal endometrium and showed a progressive increase from endometrial hyperplasia to well-differentiated carcinoma. Beyond stage 1c, strongly MRP-positive carcinoma indicated a poorer survival rate.

Ovarian actinomycosis complicated by diabetes mellitus simulating an advanced ovarian carcinoma

A patient presented with a pelvic tumor which mimicked an advanced ovarian carcinoma with invasion into urinary bladder, rectum and uterus, as detected by MR imaging. After surgery, however, actinomycosis of the left ovary was diagnosed by pathological examination. Ovarian actinomycosis in this patient was complicated by diabetes mellitus.

Ovarian dysgerminoma showing high serum levels and positive immunostaining of placental alkaline phosphatase and neuron-specific enolase associated with elevation of serum prolactin level

We report a 35-year-old Japanese female patient with ovarian dysgerminoma showing elevated serum levels of placental alkaline phosphatase (PLAP), neuron-specific enolase (NSE) and prolactin (PRL). All elevated tumor markers improved dramatically after the removal of the tumor. Immunohistochemically examined, the tumor was stained positive for PLAP and NSE and negative for PRL. Our present case is the first report of dysgerminoma showing positive immunostaining for PLAP and NSE, and the association of high serum level of PRL followed by decrease accompanied by the tumor debulking.

Recurrent clear cell carcinoma of the ovary changing into producing parathyroid hormone-related protein (PTH-rP) with hypercalcemia

We experienced the case of a clear cell carcinoma of the ovary arising from an endometrial cyst, which started to produce parathyroid hormone-related protein (PTH-rP) in a recurrent tumor, thus inducing hypercalcemia. Using immunohistochemical analysis, we demonstrated that the primary carcinoma was immunonegative for PTH-rP, but that the recurrent carcinoma was strongly immunopositive for PTH-rP.

Intermittent, repetitive administrations of irinotecan (CPT-11) reduces its side-effects

To reduce the side-effects of irinotecan (CPT-11) while maintaining its anti-cancer effects against recurrent ovarian carcinomas, we devised a novel administration schedule for CPT-11 single chemotherapy. It consisted of an initial dose of 70 mg/m2, followed by increasing the dose to 100 mg/m2 every 10 days (three times per month) for 9 cycles. Nineteen patients with refractory or recurrent ovarian carcinomas were treated. In comparison with a late phase II study of single CPT-11 chemotherapy in Japan (100 mg/m2 every 7 days; four times per month), the number of patients who suffered from leukocytopenia and diarrhea higher than grade 3 was significantly lower with our new method (36.8 versus 57.1%; P < 0.01 and 0 versus 19.2%; P < 0.001, respectively). The total response rate was 26% (5/19). This rate was almost equal to a late phase II study. We suggest that our new protocol of single CPT-11 administration should be available clinically to all patients for reducing the side-effects while maintaining its anti-cancer effects. CPT-11 is useful in patients with refractory ovarian carcinomas as a second- or third-line chemotherapy.

Gynecologic malignancies accompanied by benign hormone-dependent diseases.

Objective To investigate the correlation between benign gynecologic diseases and hormone-dependent malignancies such as endometrial carcinoma in postmenopausal women. Design We retrospectively analyzed the prevalence of myoma uteri and adenomyosis uteri in 136 cases of endometrial carcinomas. We used 222 uterine prolapse cases as controls. Results The results showed that 21.6% and 9.9% of healthy postmenopausal women (control) had myoma uteri and adenomyosis uteri, respectively, after the cessation of menses. However, postmenopausal women with endometrial carcinomas had a 1.5-to 2-fold higher prevalence, respectively, for myoma uteri and adenomyosis uteri as compared with the postmenopausal control women. Conclusion There was a higher prevalence of myoma uteri and adenomyosis uteri in postmenopausal patients with endometrial carcinomas than in the control population.

Two kinds of endometrial neoplasia arising from different origins in the uterine corpus: comparison of p53 expression and sex steroid receptor status.

This study presents a case of endometrial clear cell adenocarcinoma complicated by complex atypical glandular hyperplasia surrounded by adenomyosis in the uterine myometrium. The former was immuno-negative for estrogen receptor (ER) and positive for p53, whereas both of the latter were immuno-positive for ER and negative for p53. Therefore, there were two kinds of neoplasia arising from different origins in the uterine corpus.

Management of malignant ovarian tumors in young women. 21 nulliparous cases.

To evaluate the management of malignant ovarian tumors in young women who wish to maintain fertility, we retrospectively reviewed ovarian malignancies in 21 young women who were both nulliparous and under 40 years of age. With stage 1a disease, all 9 patients were treated with conservative surgical therapies, and all of them are still alive, irrespective of histological type. With stage 1c disease, 5 (83%) of 6 patients were treated with conservative surgical therapies. Among them, 2 patients with epithelial tumors, who were treated with conservative surgical therapies and potent cis-diamminedichloroplatinum (CDDP)-based combined chemotherapies, are still alive. Furthermore, one of them had a successful pregnancy. On the other hand, 3 out of 4 patients with nonepithelial tumors were treated with conservative surgical therapies. However, 2 (67%) out of 3 died; both of them were treated with non-CDDP-based chemotherapy. In 6 patients with disease beyond stage 2, 4 (67%) were treated with radical surgical therapies, but 2 (33%) were treated with conservative surgery and CDDP-based combined chemotherapy, one of which was followed by a successful pregnancy in spite of nonepithelial tumor. As above, we could obtain some successful pregnancies in cases beyond stage 1c after conservative surgery by adding definite CDDP-based combined chemotherapy. However, we must carefully select the patients with nonepithelial tumors for conservative therapy by adding definite CDDP-based combined chemotherapy and inform them of the risks of therapy.