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The effects of Estracyt®, HN2 (nitrogen mustard) derivative of estradiol-17β, and free HN2 on the cell kinetics of the estrogen receptor (ER) positive human endometrial cancer cell line HEC-1, were investigated using flow cytometry. HN2 at 1 μg/ml showed a marked increase in the S phase and a decrease in the G0 + Gi phase. However, with equivalent doses of Estracyt® at 10 μg/ml, the accumulation in the G2 + M phase was even more marked. Synchronization in the S phase with methotrexate (MTX) showed no increase in sensitivity to these drugs. The above results suggest that the free HN2 has an effect regardless of the cell cycle phase, whereas the effects of Estracyt® may depend on a fixed population of target cells existing in the G0+G1, S and G2 + M phases. Synchronization in the G1 phase with sodium n-butyrate could increase the target effects of Estracyt® in the S phase.

Objectives: The aim of the present study was to investigate the effectiveness of sorting fetal nucleated red blood cells (FNRBC) from maternal peripheral blood, particularly during early gestation periods, by a combination of specific gravity centrifugation and magnetic cell sorter (MACS). Methods: Without prior knowledge of the gender of the fetus, we determined gender by analyzing a Y-chromosome specific sequence by nested-PCR, using 10 ml of the peripheral blood of healthy primigravida women at different stages of gestation (first trimester: n = 17, second trimester: n = 13, and third trimester: n = 19). The results of this prenatal sex determination were compared to the sex of newborns. Results: The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of the present method during the first trimester were 100, 81.8, 100, and 75%, respectively; during the second trimester, 80, 50, 80, and 50%, respectively; and during the third trimester, 25, 63.6, 53.8, and 33.3%, respectively. Conclusion: The results show that this prenatal sex determination method has a highly accurate diagnostic rate during the first trimester, suggesting that it could be developed as a practical, non-invasive prenatal diagnostic technique for use during early gestation periods.

We describe here the case of an 82-year-old woman presenting with a hemorrhagic tumor on the anterior vaginal wall. She was diagnosed with malignant fibrous histiocytoma (MFH) from the findings of cytological analysis of biopsied surface tissue, histopathologic analysis of biopsied tissue, immunohistochemical staining, and electron microscopy. Cytological analysis of the biopsy sample harvested from the tumor surface showed multinucleated giant cells and large atypical cells with rough, granular, chromatin, as well as notable nucleoli. A storiform pattern was observed histopathologically, and immunohistochemical staining confirmed positive reactions to alpha 1-antichymotripsin (alpha 1-ACT), vimentin, and lysosome, but negative reactions to epithelial membrane antigen (EMA), cytokeratin, and alpha-smooth muscle action (alpha-SMA). Electron microscopy showed histiocyte-derived cells with a segmented nucleus with a large groove, pseudopodic cytoplasmic projections, and lysosome-like structures. However, intercellular adhesion factors were not notable, and microvilli were absent. Based on the above findings, a diagnosis of MFH originating from the vaginal wall was made. Because of the patient's advanced age, and, in accordance with her wishes, three courses of cancer chemotherapy, consisting of doxorubicin hydrochloride, fluorouracil, and cisplatin were carried out, without surgery. No reduction in the size of the tumor was seen at follow up, and despite the absence of metastasis and no exacerbation of her general condition, she died suddenly at home 2 years after being discharged.

目的:CAS200画像解析装置およびAutopapシステムを用いて子宮頸癌細胞診自動化スクリーニングの基礎的検討を行った.方法:子宮頸癌集団検診受診者, 1481例より子宮頸部搾過検体を採取し標本を作製した. 作製した標本をCAS200画像解析装置にて測定し, 測定結果を日本臨床細胞学会認定細胞検査士によって判定された細胞診判定結果と比較検討した. 次いで日本臨床細胞学会認定細胞検査士が鏡検し, すでに結果が判明している集団検診検体3232検体に対し, AutopapシステムのPrimary Screening用programを用いて検査対象の75%を要再検 (PS-Review) とする設定により検討を行った.成績:CAS200画像解析装置を用いて子宮頸癌集団検診受診者, 計1481例に対し子宮頸癌細胞診自動化スクリーニングを行った結果, 正診率は87.0%, 偽陽性率は13.7%であり, 偽陰性率は4.4%であった.Autopapにより測定された全検体数は, 3232検体であり, この中で測定可能検体は, 2741検体 (84.8%), 測定不能検体は491検体 (15.2%) であった. 測定可能であった2741検体の内, No Further Reviewと判定された検体は, 540検体 (19.7%) であり, CT Reviewと判定された検体は, 2201検体 (80.3%) であった. CT Review2201検体におけるランキング別の陰性, 陽性検体の割合は, それぞれ陰性2181検体 (99.1%) と陽性22検体 (0.9%) であった. しかし, 22検体中におけるClass VあるいはClass IIIaと判定された2検体は低いランクにとどまった.結論:Autopapシステムによる子宮頸癌細胞診自動化スクリーニングのためには, 1) 測定不能検体を少なくするためのより良い標本作成法の開発, 2) ソフトの改変による『しきい値』の改善 (50%以下), 3) 細胞診の異型度とAutopapのランキングの相関性についての検討が必要であると考えられた.

Ovarian tumors with osteoclast-like multinucleated giant cells are rarely encountered, and the existence of osteoclast-like giant cells in ovarian tumors may have no effect on the patients' prognosis. We report a patient with ovarian serous adenocarcinoma containing osteoclast-like multinucleated giant cells in the anaplastic areas of the tumor, who had a poor prognosis. A recurrent tumor showed the same anaplastic appearance as that of the primary tumor, with osteoclast-like giant cells. Forty-one percent of tumor cells were positive for MIB-1 (Ki-67) antigen, and many cells overexpressed p53 protein. However, the giant cells were negative for both antigens, which meant that they were non-cycling cells. The giant cells were also negative for epithelial and non-epithelial antigens. The multinucleated osteoclast-like giant cells, as well as mononucleated tumor cells around the giant cells, expressed p21 (WAF1/ClP1) protein. These findings suggest that the multinucleated osteoclast-like giant cells in this tumor originated from the p21-expressing mononuclear tumor cells. The coexistence of anaplastic foci with multinucleated giant cells in serous adenocarcinomas of the ovary may indicate a poor prognosis.

A case of a right ovarian tumor in a 64-year-old patient showing high blood levels of alpha-fetoprotein (AFP) is reported. Histologically, the tumor resembled hepatocellular carcinoma with hyaline globules. Localization of AFP was detected by the immunoperoxidase method. Electron microscopically, the rough-surfaced endoplasmic reticulum had developed into a meshwork, and the mitochondria were present within this meshwork. Because a transition from adenocarcinoma to a region resembling hepatocellular carcinoma was observed, this tumor was considered to originate as a common epithelial carcinoma. In the blood, 67% of the AFP was bound with concanavalin A (Con A), and the fraction pattern obtained by lentil agglutinin affinity chromatography (LCA) was of the germ cell type. From these results, the current case may be labeled clinicopathologically a hepatoid carcinoma of the ovary as described by Ishikura and Scully.

Four cases of ovarian cancer (mucinous cystadenocarcinoma, serous cystadenocarcinoma, endometrioid carcinoma and metastatic cancer of the colon) which revealed diffuse localization of carbohydrate antigen 19-9 (CA 19-9) in their tumor tissues were subjected to immunoelectron microscopy. In all cases CA 19-9 was present in plasma membranes, microvilli and glycocalyx in mucinous and metastatic carcinoma, indicating that the antigenic determinant for CA 19-9 is sialylated Lewis A. Reaction products were seldom seen in perinuclear spaces and endoplasmic reticula. Many pictures revealed positive vesicles apparently released from the Golgi apparatus; this feature seemed to be characteristic of the findings. Thus, the Golgi apparatus is considered to be the place where immunoreactive CA 19-9 is first produced in cancer cells. Since positive images were found not only in organelle but also on collagen fibers directly under the basement membranes, it seemed that an important factor for CA 19-9 increase in the blood is the expansion of CA 19-9 to stroma.It was strongly suggested that CA 19-9 was useful as a tumor marker for ovarian cancer which originated in common epithelial cells.

Immunohistochemical localization of Tumor Antigen 4 (TA-4) in squamous cell carcinoma (SCC) tissues of the uterine cervix was studied by means of the immunoperoxidase methods. Light microscopic detection of TA-4 was carried out by means of the avidin-biotin-peroxidase complex method on formalin-fixed paraffin-embedded sections from 92 cases of invasive cervical cancer of the uterus. These tumors were histologically SCC, consisting of 68 of the large cell non-keratinizing (LNK) type and 24 of the keratinizing (K) type. TA-4 positive cells were detected in 65% of LNK cases and 100% of K cases. Positively stained neoplastic cells were seen frequently around the hyperparakeratotic lesions, and they showed a tendency to keratinization.TA-4 localization was also confirmed in the cells of stratum spinosum of the non-cancerous squamous epithelium.Subcellular localization of TA-4 was studied by the preembedding indirect immunoperoxidase method. TA-4 was localized in the cytosols of the neo-plastic cells, but not in tonofilaments. It was suggested that TA-4 was a structural protein of SCC. Therefore, unlike keratin, TA-4 can be considered as an index of differentiation of SCC cells, and TA-4 should be useful as a tumor marker which expresses the characteristics of the neoplastic tissue during squamous maturation.

It has been reported that the response of target cells to steroid hormone (SH) stimulation may depend on their position in the cell cycle. The DNA and RNA contents of malignant cells of the endometrium cultured in vitro were measured using flow cytometry (FCM). We also measured estrogen receptor (ER) and progesterone receptor (PR) levels of cells at different positions in the cell cycle. The G1 and S phases of the cell cycle were investigated using cells synchronized by sodium n-butyrate (G1 block), methotrexate (S block), and excess thymidine (S block). For DNA measurements, the cells were stained with propidium iodide following RNase treatment. For RNA measurements (double-straded RNA) the cells were treated with DNase. We found that S phase synchronization by methotrexate was 136.2% of control (100%). Using the excess thymidine block and release procedure, the S phase fraction was 185.1% of control. G1 phase synchronization by sodium n-butyrate was 134% of control. The estrogen receptor level in G1 phase synchronized cells increased to 5.94 fmol/μg DNA in the cytosol and 12.35 fmol/μg DNA in the nuclear fraction. These levels represent a sevenfold total increase over that of the control estrogen receptor level. Cells in S phase showed no significant increase in estrogen receptor levels over control cells. Based on this study, the functional increase of the steroid receptor was most significant in the G1 phase.

The cytologic findings of a hemangioendotheliomaof the uterine cervix are reported. Vaginal and cervical smears were initially diagnosed as suspiciousfor malignancy, then the atypical cells in these specimen were diagnosed as the tumor cell by a induction from observation of imprint and histologicalsections of the cervical hemangioendothelioma.The cytomorphological findings of the tumor cellin vaginal and cervical smears are as follows:1. Structure of nucleus: Round or oval nucleiwith thin nuclear membranes and small unequalchromatin granules. A few small nucleoli are bluishred.2. Nuclear size: 12.5-10.0μ×10.0-7.5μ.3. N/C ratio: Moderately increased.4. Shape of cell: Polymorphic. Occasionally it ispossible to find a pseudopod-like projection.5. Appearance and staining reaction of cytoplasm;Thin and greensh-blue.

1553 women over 30 years of age were tested for uterine cancer. 72 (4.6%) of these women had had the IUD inserted and had worn the device for an average of 3.1 years. 46 (64%) patients had Class 1 Papanicolaou smears and 2 (2.8%) had Class 3 smears compared with 42% Class 2 smears 6.2% Class 3 smears and .5% Class 4 smears in the non-IUD group. It is concluded that the arguments used by those opposing the use of IUDs on carcinogenic grounds are flimsy.

We investigated the G1 and S phases of synchronization using sodium n-butyrate, MTX and excess thymidine. The flow cytometry system was employed for cell cycle analysis while the receptor assay was adopted dextran coated charcoal (DCC) and the wash method. The results were as follows: S phase synchronization by MTX was 138% (control 100%) and by excess thymidine in the block and release method 210%. G1 phase synchronization by sodium n-butyrate was 140%. The progesterone receptor level, by E2 priming increased to 1.45 fmol/ug DNA being more than five times that of the control PR. The estrogen receptor level increased to 18.29 fmol/ug DNA in the G1 phase synchronization, seven times that of the control ER. From this study, the functional increase of the steroid receptor was most significant in the G1 phase.