Motoi Sasagawa

Immunohistochemical localization of HLA antigens and placental proteins (αhCG, βhCG CTP, hPL and SP1 in villous and extravillous trophoblast in normal human pregnancy: a distinctive pathway of differentiation of extravillous trophoblast

Abstract Immunohistochemical localization of HLA antigens and plancental proteins (αhCG, βhCG CTP, hPL and SP 1 ) in villous and extravillous trophoblast at various stages of normal human gestation were studied, using hysterectomy specimens. In the chorionic villi, the capacity for synthesizing placental proteins seemed to develop in parallel with the morphological change from mononuclear cells to multinucleated syncytiotrophoblast and no villous trophoblast expressed HLA antigens. In contrast, extravillous trophoblast, including the multinucleated trophoblastic cells at the deciduomuscular junction, expressed HLA-A, -B, and -C, and their capacity for synthesizing placental proteins did not seem to correspond with the degree of morphological change: the location of αhCG, βhCG CTP and SP 1 was restricted to mononuclear trophoblast in the superficial decidua, while hPL was present extensively in extravillous trophoblast. These findings strongly suggest that extravillous trophoblast possesses many distinctive biological features and differentiates in an independent manner. Mononuclear trophoblast forming the cell columns was also positive for HLA-A, -B, and -C, and no placental protein was demonstrated in these cells; this, together with previous morphological observations, may indicate the germinative nature of these cells.

Reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) on human tissue sections: analysis of their usefulness as a histological trophoblast marker in normal pregnancy and trophoblastic disease

In normal and molar pregnancy, a morphological discrimination between nonvillous trophoblasts which lie scattered in the placental bed and surrounding maternal cells is considered to be difficult. We examined the reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) against cytokeratin by an immunoperoxidase technique and analyzed their usefulness as a histological trophoblast marker. Materials were taken from 42 uteri with normal pregnancy, 7 uteri with hydatidiform mole, 2 uteri with gestational choriocarcinoma, 1 fallopian tube with nongestational choriocarcinoma, 5 delivered term placentae of normal pregnancy, and 5 nongestational uteri. The reactivities of Troma 1 on frozen sections and those of CAM 5.2 on paraffin sections were identical. They reacted with surface epithelium and gland epithelium in the nongestational uterine corpus. In the implantation site of normal and molar pregnancy, they reacted with villous and nonvillous trophoblasts as well as endometrial gland epithelium. In gestational and nongestational choriocarcinoma, they reacted with carcinoma cells specifically. Since the histological detection of gland epithelium may not be difficult, it was concluded that the two antibodies were very beneficial as a histological marker for trophoblasts in normal pregnancy and trophoblastic disease.

Immunohistochemical studies of fetal trophoblast and maternal decidua in hydatidiform mole and choriocarcinoma

Immunohistochemical techniques have been used to investigate the expression of fetal trophoblast antigens and the maternal leucocytic response in molar pregnancy and choriocarcinoma. The antigenic phenotype of morphologically defined trophoblast populations in complete, partial and invasive moles was analogous to that in normal pregnancy. All trophoblast phenotypes described in normal pregnancy were also identified in choriocarcinoma, suggesting that extensive differentiation into heterogeneous subgroups occurs in malignant trophoblast. The maternal leucocytic infiltrate in molar pregnancy consisted of T lymphocytes and class II MHC-positive macrophages. CD2-positive, CD3-negative lymphocytes were identified in molar decidua but not in uterine tissue in choriocarcinoma. Similarly, endometrial granulocytes were present in molar decidua but not in choriocarcinoma; these cells were associated with decidualization rather than with fetal trophoblast.

Clinical evaluation of focal excision of myometrial lesion for treatment of invasive hydatidiform mole.

To determine the clinical significance of conservative surgical therapy, namely focal excision of myometrial molar deposits, 22 patients with invasive hydatidiform mole (HMI who had received the therapy were analysed for their postoperative clinical course and reproductive performance. They were operated on because of their prolonged HCG regression curve and the presence of abnormal shadows in the uterine wall revealed by pelvic angiography, ultrasonography and computerized tomography after evacuation of intra‐uterine molar tissue. A definitive diagnosis of invasive HM was established histopathologically in all of the extirpated materials. Seven of the patients were given postsurgical chemotherapy because of prolongation of their HCG decrease after the operation. The following items were emphasized as necessary criteria when selecting patients for surgery consisting in complete resection of the myometrial lesion: (1) urinary HCG titers below 10,000 IU/day; (2) no evidence of pulmonary metastatic involvement; or (3) metastases in the lungs, controlled with chemotherapy prior to the operation. Their reproductive performance was almost the same as that of comparable patients who were treated by chemotherapy alone.

Origin of adenocarcinoma cells observed on cervical cytology

OBJECTIVE To clarify the ratio of diseases suspected when malignant glandular cells are observed on cervical cytology. STUDY DESIGN Seventy cases of cervical adenocarcinoma/adenosquamous carcinoma, 207 cases of endometrial adenocarcinoma, 7 cases of tubal adenocarcinoma and 83 cases of ovarian adenocarcinoma were reviewed. The positive rate in cervical cytology performed 3 months before surgery was calculated. Based on the positive rate for each entity and the number of cases treated in the previous 10 years, we estimated the incidence of disease responsible for malignant glandular cells on cytology. RESULTS The positive rate was 93% in cervical adenocarcinoma/adenosquamous carcinoma, 45% in endometrial adenocarcinoma, 14% in tubal adenocarcinoma and 6% in ovarian adenocarcinoma. These positive rates and case numbers at our institute indicated the percentage of suspicious diseases to be 38% for cervical aaenocarcinoma/adenosquamous carcinoma, 53% for endometrial adenocarcinoma, 1% for tubal adenocarcinoma and 8% for ovarian adenocarcinoma. CONCLUSION When a cytologic specimen suggested the existence of adenocarcinoma, the most probable disease was endometrial adenocarcinoma, and the second was cervical adenocarcinoma/adenosquamous carcinoma. Adnexal malignancies were responsible in 9% of cases. In the case of positive cervical cytology suggesting adenocarcinoma, the ratio of suspicious diseases is as valuable as the cytologic findings for the differential diagnosis.

HLA Expression by Trophoblast of Invasive Moles

HLA expression by the trophoblast in invasive hydatidiform mole was analysed by immunoperoxidase staining. In the invading villi of an invasive mole, villous trophoblast, both syncytiotrophoblast and cytotrophoblast, failed to show a positive reaction for HLA-A, -B and -C and HLA-DR. By contrast, extravillous trophoblast showed an intense reaction for HLA-A, -B and -C. The distribution of HLA antigens in the invading villi was the same as in the non-invading villi, and the antigens were also indistinguishable from those noted in non-invasive hydatidiform moles. The histopathology of invasive mole may suggest that it is a malignant neoplasm. This immunohistochemical study, however, lends support to the current view that invasive mole is a variant of a benign hydatidiform mole rather than a form of malignant trophoblastic disease.

Clinical problems of invasive hydatidiform mole in patients aged 40 or more

Seventy-six patients with invasive hydatidiform mole (HM) were reviewed as to clinical course, particularly treatment and outcome, in relation to their age. The results were as follows: (i) metastatic cases showed approximately a twofold increase in patients over 40 compared with younger patients, (ii) more courses of chemotherapy were required to achieve a cure in patients over 40 than in younger patients and (iii) 4 of 19 patients (21.1%) over 40 developed choriocarcinoma, whereas none of younger patients did.

Efficacy and safety of the traditional Japanese herbal medicine kamikihito for bone marrow suppression, particularly thrombocytopenia, during chemotherapy for advanced recurrent ovarian cancer

The aim of this study was to evaluate the efficacy and safety of the traditional herbal medicine kamikihito for bone marrow suppression, particularly thrombocytopenia, during cancer chemotherapy.

Two cases of endometrial cancer arising from adenomyosis during aromatase inhibitors therapy after mastectomy

Among gynaecological neoplasms, both adenomyosis and endometrial cancer are encountered relatively often. However, endometrial cancer arising from adenomyosis is considered rare (Kumar and Anderson 1958; Colman and Rosenthal 1959; Koike et al. 2013). We, herein, report our experience with two cases of this disease in patients taking oral aromatase inhibitors (AIs) after mastectomy. Although this disease has occasionally been reported, there have been few reports suggesting the risk factors for occurrence of this condition or effective treatment, whereas our present report focuses on this issue.

Disappearance of a metastatic brain tumor and achievement of long-term survival with a good quality of life after a combination of systemic chemotherapy with the P-glycoprotein inhibitor nifedipine in a patient with ovarian cancer

Dear Editor, Systemic chemotherapy has not been established for metastatic brain tumors from primary ovarian cancer. Here, we report our experience with an important case in which the efficacy of systemic chemotherapy was enhanced and prolonged survival with a good quality of life (QOL) was achieved by using nifedipine to inhibit P-glycoprotein. The patient was a 53-year-old woman. In July 1998, she underwent an optimal surgery for stage IIIc ovarian cancer (serous adenocarcinoma). In August 2006, the disease recurred as metastasis in the para-aortic lymph nodes. Although these lesions disappeared after chemotherapy with paclitaxel plus carboplatin (CBDCA), four metastatic brain tumors were observed in July 2007: a lesion in the cerebellar vermis; an asymptomatic nodular lesion in the left basal ganglion; and an asymptomatic nodular lesion in the right and left cerebellar hemisphere, each. These lesions disappeared after Gamma Knife radiosurgery. In June 2008, yet another asymptomatic metastatic lesion was found in the cortex of the apical portion of the right temporal lobe, which disappeared after Gamma Knife radiosurgery. However, in March 2011, another asymptomatic metastatic lesion (8×5 mm) was observed in the medial portion of the sensory region of the right parietal lobe (Fig. 1a). We opted to administer systemic chemotherapy, anticipating that it would not only have therapeutic effects on brain metastases but also exert a preventive effect against both metastasis to other organs and recurrence. Pegylated liposomal doxorubicin (PLD) plus CBDCA, which has been shown to be effective for recurrent ovarian cancer, was selected. However, because of the previously reported poor outcomes for brain metastasis from primary ovarian cancer [3], we decided to combine PLD plus CBDCA with nifedipine in the hope of increasing the anti-cancer drug efficacy. The patient provided informed consent and was prescribed a sustained-release nifedipine tablet (20 mg) to be taken every morning and evening for 7 days, starting on day 1 of each cycle of chemotherapy. After two cycles, contrast-enhanced magnetic resonance imaging (MRI) showed a 75 % reduction in lesion size (Fig. 1b). After four cycles, the lesion was no longer visible on contrast-enhanced computed tomography (CT) (Fig. 1c). After five cycles, its disappearance was confirmed by contrast-enhanced MRI (Fig. 1d). The serum cancer antigen 125 level, which was 162.7 U/ml initially, normalized to 19.3 U/ml after three cycles. There were no variations in blood pressure during nifedipine treatment and no adverse events such as palpi tations, nausea, or facial f lushing. The chemotherapy-related adverse events were minor. Treatment was completed after seven cycles in November 2011. As of this writing, the patient is completely independent in her activities of daily living, with a performance status of 0. She has a good QOL and is under outpatient management. * Toru Yanase toyanase@gmail.com