Intermediate Trophoblast Research Articles

Implantation site intermediate trophoblasts in placenta cretas

Placenta cretas are defined as abnormal adherences or ingrowths of placental tissue, but their pathogenetic mechanism has not been fully explained. During histologic examination of postpartum uteri, we noticed that the number of implantation site intermediate trophoblasts was increased in the placental bed of placenta cretas. To validate our observation and to address the pathogenetic role of implantation site intermediate trophoblasts in placenta cretas, we examined postpartum uteri with placenta cretas (n=34) and noncretas (n=22), obtained from Cesarean or immediate postpartum hysterectomy specimens. Using antibody to CD146, a marker for implantation site intermediate trophoblasts, we found that placenta cretas had significantly thicker layer of implantation site intermediate trophoblasts (2300±1200 μm) than noncretas (1500±1200 μm, P<0.025). We also observed that the confluent distribution of cells was more frequent in placenta cretas (97%) than noncretas samples (45%, P<0.001), and that the total number of implantation site intermediate trophoblasts within the superficial myometrium of the placental bed was significantly higher in placenta cretas than noncretas. Using antibodies to Ki-67, Bcl-2 and cleaved caspase-3 to determine the proliferative index and apoptotic rates of implantation site intermediate trophoblasts, we found that they were close to zero in both groups and did not differ significantly. These findings suggest that the increased number of implantation site intermediate trophoblasts observed in placenta cretas may be related to the pathogenesis of placental ingrowth, but the mechanism by which the increase in implantation site intermediate trophoblasts causes placenta cretas remains to be clarified.

Expression pattern of the CCAAT/enhancer-binding protein C/EBP-beta in gestational trophoblastic disease.

The CCAAT/enhancer-binding protein (C/EBP) family consists of several factors that are important regulators of intracellular processes and hormone action. C/EBP-beta, the most important member of the C/EBP family, was shown recently to be expressed in the normal human placenta where it is localized in villous syncytiotrophoblast and in the extravillous (intermediate) trophoblast but not the villous cytotrophoblast. The purpose of this study was to investigate the expression pattern of C/EBP-beta in gestational trophoblastic disease (GTD) which has not been studied so far. We used immunohistochemistry on a total of 15 cases of GTD including nine complete hydatidiform moles, one placental site nodule (PSN), one placental site trophoblastic tumor (PSTT), and four choriocarcinomas. All our tested specimens showed positivity for C/EBP-beta. The strongest C/EBP-beta expression could be observed in villous syncytiotrophoblast and in the trophoblast proliferations on the villous surface of hydatidiform moles; villous cytotrophoblast was negative. The PSN also showed positive nuclear staining but the expression was not as strong as it was in the hydatidiform moles and the total amount of stained cells was the lowest of all GTD. The PSTT also showed immunoreactivity but with a weaker and more heterogeneous staining than in the choriocarcinomas. The specific expression pattern of C/EBP-beta in GTD indicate that C/EBP-beta could potentially be an additional marker of such lesions.

Placental Site Trophoblastic Tumor: A Case of Extensive Pulmonary Metastasis

INTRODUCTION: Placental site trophoblastic tumor (PSTT) is an uncommon variant of malignant gestational trophoblastic disease (GTD) that arises from intermediate trophoblast cells, producing relatively low levels of b-hCG and hPL, and are frequently resistant to chemotherapy. We report a case of PSTT with extensive pulmonary involvement and polycythemia, without known genital tract disease.

P63 expression is useful in the distinction of epithelioid trophoblastic and placental site trophoblastic tumors by profiling trophoblastic subpopulations.

Human trophoblast is composed of a heterogeneous population of cells, which give rise to a variety of trophoblastic tumors and tumor-like lesions. In this report, we analyzed the expression pattern of the p63 gene, a transcription factor belonging to the p53 family, in different trophoblastic subpopulations and in trophoblastic lesions. p63 has various isoforms that are classified into two groups designated TA and DeltaNp63 isoforms. The TA isoforms have a p53-like suppressor function, whereas the DeltaNp63 isoforms exert an oncogenic effect. Based on immunohistochemistry and RT-PCR, it appears that cytotrophoblast expresses the DeltaNp63 isoform whereas chorionic-type intermediate trophoblast in the fetal membranes, placental site nodules, and epithelioid trophoblastic tumors expresses the TAp63 isoform. Intermediate trophoblast in the implantation site and placental site trophoblastic tumors does not express p63. Based on the expression patterns of p63 and the previously described expression patterns of other trophoblastic markers, including HLA-G, cytokeratin 18, hPL, and Ki-67, we developed an immunohistochemical algorithm to diagnose trophoblastic lesions. A validation set of 22 trophoblastic lesions and 34 nontrophoblastic tumors were classified correctly using this algorithm. In conclusion, the findings in this study demonstrate that different trophoblastic subpopulations and their related trophoblastic lesions are characterized by distinctive patterns of p63 expression. Recognizing these distinctive expression patterns helps to further elucidate the biology of trophoblast and can also provide a useful tool for the differential diagnosis of trophoblastic lesions.

Postpartaler Uterustumor unklarer Dignität: „Placental Site Nodule“ - eine Falldarstellung

Postpartale Uterustumoren können unterschiedlicher Herkunft sein und eine entsprechend variable Dignität aufweisen. Wir beschreiben den Fall eines unmittelbar postpartal aufgetretenen Uterustumors, welcher trotz mehrfacher Kürettagen persistierte und im Verlauf eine Endomyometritis verursachte. Der Tumor zeigte eine mäßige β-HCG-Produktion, war intermediär sensibel auf Methotrexat und führte nach einem halben Jahr Beobachtungszeit zu starker vaginaler Blutung. Sonographisch zeigt sich der Tumor als schalldicht, inhomogen und mit der Doppler-Untersuchung konnte eine verstärkte Durchblutung im Tumor nachgewiesen werden. Erst durch die laparoskopisch durchgeführte Abtragung des Uterushorns, in welchem der Tumor lokalisiert war, konnte der Befund vollständig entfernt werden. Die histologische Diagnose, welche auch nach mehrfacher Kürettage und Biopsie der Läsion nicht gestellt werden konnte, ergab einen „Placental Site Nodule (PSN)“, ein benigner Tumor aus der Familie der Intermediärtrophoblast (IT)-Tumoren.

Immunohistochemical characterization of p57Kip2 expression in tetraploid hydropic placentas.

Because there are differences in the origin, morphology, and natural history of hydropic placental villous issues, it is important to identify and document rare specimens that deviate from the diploid complete hydatidiform mole (CM), triploid partial hydatidiform mole (PM), or diploid hydropic abortion (HA). Tetraploid hydropic placentas have rarely been studied. To evaluate the frequency of p57Kip2 protein (p57) expression in tetraploid hydropic placentas and to determine its clinicopathologic significance. Forty hydropic DNA tetraploid placental specimens were evaluated by immunohistochemistry of formalin-fixed tissues, using a monoclonal antibody against p57, a putative paternally imprinted inhibitor gene. DNA ploidy in all cases was analyzed by flow cytometry. Thirty cases were histologically diagnosed as CMs, 10 were HAs, and none were PMs. In all HAs, nuclear p57 was strongly expressed in cytotrophoblasts, intermediate trophoblasts, and villous stromal cells. In contrast, in CMs, p57 expression in cytotrophoblasts and villous stromal cells was either absent (26 cases) or very low (4 cases). Assuming that the degree of molar change roughly correlates with the proportion of paternal chromosomes present, all chromosomes might be paternally derived in all tetraploid CMs and the 10 HAs, including 2 that were karyotyped as 92,XXYY or 90,XXYY,-13,-14, which were presumably due to 2 sets of chromosomes each from paternal and maternal origin. Expression of p57 is aberrant in tetraploid CMs. This finding is in line with the hypothesis that the loss of p57 is involved in the abnormal development of androgenetic CMs. For the evaluation of a patient with trophoblastic disease, p57 immunostaining is an ancillary diagnostic method that may be used in concert with flow cytometry.

Immunohistochemical characterization of cyclin E and p27KIP1 expression in early hydatidiform moles.

The aim of this study is to evaluate whether the expression of p27 (p27) and cyclin E (cE) is related to the development of hydatidiform moles and whether their expressions are associated with prognosis in these lesions. Ten diploid voluntary artificial abortions (ABs), 20 diploid hydropic abortions (HAs), 20 triploid partial moles (PMs), and 44 diploid complete moles (CMs) (including 4 with persistent disease), all of which were in the first trimester, were evaluated by immunohistochemistry of formalin-fixed tissues using monoclonal antibodies against p27 and cE protein. DNA ploidy in all cases was analyzed by flow cytometry. In ABs, nuclear cE was expressed at low (1+) to moderate (2+) levels in cytotrophoblast (CT), intermediate trophoblast (IT) and occasionally in syncytiotrophoblast (ST). In all CMs, cE-positive nuclei of CT were observed at high levels (3+), and (1+) to (2+) levels in clusters of IT. On the other hand, all HAs and PMs showed cE levels comparable to those observed in ABs. There was a significant difference in cyclin E expression in CT between CMs and non CMs, but there was no significant difference of cE levels between CMs with and without persistent disease. In 3 of 10 ABs, nuclear p27 was expressed at (1+) levels in ST. Similar expression was observed in 27 (including 2 invasive lesions) of 44 CMs, 10 of 20 PMs, and 8 of 20 HAs. CT and IT were rarely positive (1+) for p27 in the cases examined. Decidual stromal cells provided a reliable positive internal control for p27 expression. These findings support the hypothesis that trophoblast proliferation is related to the balance between the positive cell cycle factors, such as cE, and the negative cell cycle inhibitors, such as p27. The overexpression of cE in the trophoblastic elements suggests that cE protein expression may be dysregulated in early CMs. Neither cE nor p27 expression is a prognostic indicator in CMs.

Gestational trophoblastic disease. Non-villous forms of gestational trophoblastic disease

The non-villous forms of gestational trophoblastic disease (GTD) include a wide range of morphologic different lesions and cover a wide range of differential diagnosis. Choriocarcinomas (CCA) represent the most malignant form displaying a dimorphic pattern with proliferation of syncytio- and zytotrophoblast. An early start of chemotherapy is of great prognostic impact. Placental site nodule (PSN) and exaggerated placental site (EPS) are non-neoplastic lesions of the intermediate trophoblast without tumorous appearance, whereas placental site trophoblastic tumor (PSTT) and epitheloid trophoblastic tumor (ETT) represent tumorous neoplasms with a potential for local invasion and metastases. PSNs are incidental findings of highly polymorphic cells. In EPS chorionic villi are almost present, endometrial glands and spiral arteries are completely engulfed by intermediate trophoblastic cells without necroses. In PSTT the monomorphic, occasional multinucleated giant cells separating individual muscle fibers and charactersitically blood vessel walls are extensively replaced by trophoblastic cells and fibrinoid material. The ETT consists large necrotic areas with hyalinisation. Typically small blood vessels with preserved walls are located within the center of glycogen-rich monomorphous proliferation of trophoblastic cells.

Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns.

Placental examination can be a useful tool for specifying the etiology, prognosis, and recurrence risk of pregnancy disorders. The purpose of this study was to test the reliability of a predetermined set of placental reaction patterns seen with maternal vascular underperfusion in the hope that this might provide a useful diagnostic framework for practicing pathologists. Study cases (14 with clinical and pathologic evidence of maternal underperfusion plus 6 controls) were evaluated for the presence or absence of 11 lesions by eight perinatal pathologists. After analysis of initial results, diagnostic criteria were refined and a second, overlapping set of cases was reviewed. The collective sensitivity, specificity, and efficiency of individual assessments for the 11 lesions relative to the group consensus ranged from 74-93% (22/33 > 90%). Reproducibility was measured by unweighted kappa-values and interpreted as follows: < 0.2 poor, 0.2-0.6 fair/moderate, > 0.6 substantial. Kappa values for lesions affecting villi and the intervillous space were increased syncytial knots (any -0.42, severe -0.50), villous agglutination (0.42), increased intervillous fibrin (0.25), and distal villous hypoplasia (0.57). Individual estimates of percent involvement for syncytial knots, intervillous fibrin, and distal villous hypoplasia were correlated with placental and fetal weight for gestational age. Extent of increased intervillous fibrin showed the strongest correlation with both placental weight ( R = -0.64) and fetal weight ( R = -0.45). Kappa values for lesions affecting maternal vessels and the implantation site were acute atherosis (0.50), mural hypertrophy of membrane arterioles (0.43), muscularized basal plate arteries (0.48), increased placental site giant cells (0.54), and immature intermediate trophoblast (0.36). Correlation of maternal vessel and implantation site lesions with the clinical diagnosis of preeclampsia showed that excessive placental site giant cells and immature intermediate trophoblast were more sensitive and efficient predictors, whereas atherosis and muscularized basal plate arteries were more specific. Kappa value for a thin umbilical cord, a possible indicator of fetal volume depletion, was 0.61. Reproducibility for a global impression of maternal vascular underperfusion, taking into account all of the above lesions, was moderate (kappa 0.54) and improved after inclusion of additional pathologic and clinical data (kappa 0.68). Adoption of this clearly defined, clinically relevant, and pathologically reproducible terminology could enhance clinicopathologic correlation and provide a more objective framework for future clinical research.

Placental site trophoblastic tumor in a postmenopausal female—A case report

Background. Placental site trophoblastic tumor (PSTT) is tumor of intermediate trophoblast, seen commonly in reproductive age group. Case. A 63-year-old postmenopausal woman presented with vaginal discharge, occasional bleeding and a large uterine mass suspicious of malignancy. The uterus ruptured during hysterectomy. A large, necrotic and hemorrhagic tumor was seen in the endometrial cavity infiltrating through the myometrium into serosa. The tumor cells were large pleomorphic, polygonal with variable mitosis. The histological differential diagnosis included choriocarcinoma, epithelioid trophoblastic tumor, epithelioid leiomyosarcoma and poorly differentiated carcinoma. The tumor cells were positive for cytokeratin and β-hCG and negative for smooth muscle antigen and HMB-45. The final histological diagnosis was PSTT. Conclusion. PSTT is rare in postmenopausal females. It is difficult to diagnose clinically as well as histologically.

Expression pattern of the activating protein-1 family of transcription factors in the human placenta.

The human placenta is a tissue with a unique capacity for rapid, but--as opposed to malignant tumours--tightly controlled proliferation and invasion capacity. The members of the activating protein-1 (AP-1) family of transcription factors are key regulators of cellular proliferation, differentiation and invasion processes in many systems and could, thus, play an important role in regulating these processes in the human placenta as well. In the present study, we used immunohistochemistry with specific antibodies against all members of the AP-1 family (c-Jun, JunB, JunD and c-Fos, FosB, Fra-1, Fra-2) to investigate their expression pattern and tissue localization in the human placenta. With the exception of c-Jun, which was expressed in a small fraction of villous cytotrophoblast nuclei and JunD, expressed in some syncytiotrophoblast nuclei, all other members of the AP-1 family were completely absent from villous cyto- and syncytiotrophoblast. Interestingly, most AP-1 factors were expressed in the intermediate (extravillous) trophoblast, with expression being strongest for JunD and Fra2 (100% of nuclei showing strong expression), followed by c-Jun (80% positive nuclei), c-Fos and FosB (50% positive nuclei). This was true for samples of both first trimester and later pregnancy. These data show that, in the human placenta, the AP-1 transcription factors are specifically expressed in the intermediate (extravillous) trophoblast, were they could be implicated in regulating proliferation, differentiation and/or expression of invasion-specific molecules, such as matrix metalloproteinases, which have been shown to be regulated by AP-1 in vitro and are expressed by the invasive trophoblast.

Pre-eclampsia is associated with the failure of melanoma cell adhesion molecule (MCAM/CD146) expression by intermediate trophoblast

The purpose of this study was to determine whether the expression of melanoma cell adhesion molecule (MCAM/CD146), like most other endothelial adhesion molecules, is reduced in the pregnancy disorder pre-eclampsia, and whether it is associated with the invasiveness of trophoblast. We used immunohistochemical approaches and analyzed 42 placentas from control and pre-eclamptic patients using an anti-CD146 monoclonal antibody. Our data show that in normal placentas, CD146 staining was specifically detected in intermediate trophoblasts that are most invasive and migratory, but not detected in noninvasive cytotrophoblasts or syncytiotrophoblasts. However in pre-eclampsia, CD146 was no longer present in the intermediate trophoblasts, although it was detectable in the blood vessels. At the same time, we tested CD31/PECAM-1, another endothelial adhesion molecule, and found its negative staining for all kinds of trophoblasts in both normal and pre-eclamptic placentas. The different staining patterns of CD146 in the normal and pre-eclamptic placentas provide the first evidence that in pre-eclampsia, intermediate trophoblasts fail to express CD146, implicating that CD146 plays an important role in trophoblast invasion.

Comparative genomic hybridization study of placental site trophoblastic tumour: a report of four cases

Placental site trophoblastic tumour (PSTT) is a neoplastic proliferation of the implantation intermediate trophoblast. Although clinicopathological studies are not uncommon in case reports or small series, molecular and genetic studies are quite limited. Four archived cases of PSTT were successfully analysed by comparative genomic hybridization (CGH) in this study. Regional chromosomal gains were observed in two cases. One case showed chromosomal gains in the regions of 19p13.2, 21q11–21 and 22q12. The second case demonstrated a single regional chromosomal gain involving 21q21. No chromosomal loss is observed. The remaining two cases showed a balanced CGH profile without detectable chromosomal gain or loss. In summary, although chromosomal alterations detectable by CGH are not common, rare chromosomal gains do occur in PSTT. The recurrent chromosomal gain involving chromosomal 21q observed in two of our cases deserves additional studies to ascertain whether it carries any pathobiological significance.

Pre-eclampsia is associated with the failure of melanoma cell adhesion molecule (MCAM/CD146) expression by intermediate trophoblast

The purpose of this study was to determine whether the expression of melanoma cell adhesion molecule (MCAM/CD146), like most other endothelial adhesion molecules, is reduced in the pregnancy disorder pre-eclampsia, and whether it is associated with the invasiveness of trophoblast. We used immunohistochemical approaches and analyzed 42 placentas from control and pre-eclamptic patients using an anti-CD146 monoclonal antibody. Our data show that in normal placentas, CD146 staining was specifically detected in intermediate trophoblasts that are most invasive and migratory, but not detected in noninvasive cytotrophoblasts or syncytiotrophoblasts. However in pre-eclampsia, CD146 was no longer present in the intermediate trophoblasts, although it was detectable in the blood vessels. At the same time, we tested CD31/PECAM-1, another endothelial adhesion molecule, and found its negative staining for all kinds of trophoblasts in both normal and pre-eclamptic placentas. The different staining patterns of CD146 in the normal and pre-eclamptic placentas provide the first evidence that in pre-eclampsia, intermediate trophoblasts fail to express CD146, implicating that CD146 plays an important role in trophoblast invasion.

Comparative genomic hybridization study of placental site trophoblastic tumour: a report of four cases

Placental site trophoblastic tumour (PSTT) is a neoplastic proliferation of the implantation intermediate trophoblast. Although clinicopathological studies are not uncommon in case reports or small series, molecular and genetic studies are quite limited. Four archived cases of PSTT were successfully analysed by comparative genomic hybridization (CGH) in this study. Regional chromosomal gains were observed in two cases. One case showed chromosomal gains in the regions of 19p13.2, 21q11–21 and 22q12. The second case demonstrated a single regional chromosomal gain involving 21q21. No chromosomal loss is observed. The remaining two cases showed a balanced CGH profile without detectable chromosomal gain or loss. In summary, although chromosomal alterations detectable by CGH are not common, rare chromosomal gains do occur in PSTT. The recurrent chromosomal gain involving chromosomal 21q observed in two of our cases deserves additional studies to ascertain whether it carries any pathobiological significance.

Reducing Agent and Tunicamycin-responsive Protein (RTP) mRNA Expression in the Placentae of Normal and Pre-eclamptic Women

Recently, the gene encoding a new stress-induced protein termed reducing agent and tunicamycin-responsive protein (RTP) was identified. The function of RTP is unknown, however, the strong upregulation of RTP during cellular differentiation, and exposure to stress conditions including hypoxia suggests a specific role for RTP in these processes. In pre-eclampsia, impaired spiral artery remodelling and reduced perfusion may reduce oxygen tension in the placenta and thereby alter trophoblast differentiation and function. We therefore hypothesized that the expression of RTP mRNA is altered in the placentae of women with pre-eclampsia. The aims of this study were to determine the regional distribution and cellular localization of RTP mRNA expression and compare mRNA abundance in different regions of normotensive control and pre-eclamptic placentae. In normal and pre-eclamptic placentae, RTP mRNA was expressed in the syncytiotrophoblasts and in the intermediate trophoblasts of the basal plate. In early onset pre-eclampsia, RTP mRNA was more abundant in the chorionic villi regions. A further increase was localized to the syncytial knots and to the trophoblasts in the peri-infarct regions. The increased RTP expression may reflect lower oxygen tension and/or other stress stimuli in the placenta in pre-eclampsia.

Methylation status and expression of E-cadherin and cadherin-11 in gestational trophoblastic diseases

The clinical significance of cadherins in gestational trophoblastic diseases (GTD) is not fully understood. In this study, the expression of E-cadherin and cadherin-11 in 12 normal placentas, 32 cases of hydatidiform mole (HM) including 15 complete HMs and 17 partial HMs, and five choriocarcinomas was investigated by immunohistochemistry and correlated with follow-up of HMs. Cases with available frozen blocks were further analyzed by western blot and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Methylation of E-cadherin was investigated by methylation-specific PCR in six normal first trimester placentas, 19 HMs and their associated deciduas. E-cadherin expression was localized to cytotrophoblast and intermediate trophoblast whereas cadherin-11 was expressed in syncytiotrophoblast, intermediate trophoblast, and decidua. Immunoreactivity of E-cadherin was reduced in choriocarcinoma and complete HM when compared with that in normal first trimester placenta (P&lt; 0.01,P= 0.04). Hypermethylation of E-cadherin was demonstrated in three complete HMs with the lowest level of E-cadherin. Compared with normal first trimester placenta, immunoreactivity of cadherin-11 was higher in complete HM (P= 0.02), but lower in choriocarcinoma (P= 0.02). Such differential expression was confirmed by western blot and semiquantitative RT-PCR. No obvious association was observed between the development of persistent trophoblastic disease with the expression of E-cadherin and cadherin-11.

Extrauterine Lesions of Intermediate Trophoblast

Lesions of intermediate trophoblast arising in the uterus include exaggerated placental site, placental site nodule, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor. Only 12 examples of extrauterine lesions of intermediate trophoblast (ELIT) have been previously reported; 7 new cases are described herein. Six lesions were located in the fallopian tube or paratubal region and one in the ovary. The patients were 25 to 47 (average 36) years of age. The lesions ranged from 0.6 to 4 cm in diameter; four were cystic. The four placental site nodules (three tubal, one paratubal) were composed of small, sharply circumscribed nodules of intermediate trophoblast with no mitotic activity. The three PSTTs (two tubal, one ovarian) exhibited irregular stromal infiltration by intermediate trophoblast, mitotic activity, and necrosis. Chronic salpingitis was seen in the six tubal/paratubal cases, and endometriosis was seen in four cases. Immunoreactivity for human placental lactogen, human chorionic gonadotropin, and cytokeratin in two cases was consistent with an origin from intermediate trophoblast. ELITs presumably arise from previous ectopic pregnancies, a history of which was present in two of these patients. Follow-up, available on two of the three patients with PSTT, was uneventful at 6 and 12 years, but study of additional cases is necessary to reliably determine the behavior of extrauterine PSTTs.

Applications of monoclonal anti-human inhibin α subunit in endometrial curettings

<h2>Summary</h2><h3>Aims</h3> Using archival material, we studied the immunoreactivity and utility of monoclonal anti-human inhibin α subunit in the identification of chorionic villi (CV) and trophoblastic subpopulations in endometrial curettings (EC) from patients who had intra-uterine, ectopic, molar and, particularly, probable intra-uterine pregnancies. We also compared its expression with those of bHCG, HPL and CAM 5.2. <h3>Methods</h3> The four groups of EC investigated included: Group 1, 15 patients with intra-uterine pregnancies (IUP); Group 2, 15 patients with tubal pregnancies (TP); Group 3, 15 patients with hydatidiform moles (HM); and Group 4, 20 patients with purported history of intra-uterine pregnancies (PIUP). Positive and negative control cases were from Groups 1 and 3 and Group 2, respectively. The test cases were from Group 4. Immunohistochemistry was performed on each case testing for expression of inhibin α, βHCG, HPL and CAM 5.2. <h3>Results</h3> Trophoblastic populations, which included syncy-tiotrophoblast (ST), cytotrophoblast (CT) and intermediate trophoblast (IT), were absent in all 15 negative control cases (Group 2). The 30 positive control cases (Groups 1 and 3) revealed the following: (a) ST, CT and IT were identified in all cases and were positive for CAM 5.2, (b) inhibin α, βHCG and HPL (except one case) were reactive for all cases with ST, but not CT, and (c) IT positivity for βHCG, HPL and inhibin α was 67, 80–93 and 100%, respectively. From the 20 test cases (Group 4), the findings were: (a) CT was absent in all cases, (b) scattered ST cells, which were identified only in 10 cases, were positive for all antibodies, (c) scattered IT cells were present in 17 cases and showed 100% CAM 5.2 positivity, and (d) IT positivity for βHCG, inhibin α and HPL was 58.8% (10/17), 76.5% (13/17) and 82.4% (14/17), respectively. Background staining was observed in 22 of 65 cases (33.8%) stained with βHCG and HPL; half of these cases came from Group 3. Inhibin α and CAM 5.2 staining did not show this problem. <h3>Conclusions</h3> We suggest that inhibin α is a useful antibody in diagnosing IUP and HM and in documenting intra-uterine gestations in cases with PIUP because it is a sensitive marker in immunolabelling IT and ST. Combined application of inhibin α and CAM 5.2 might be more useful than βHCG and HPL because the latter showed background staining in one third of the cases.

CD10 Expression in Epithelial Tissues and Tumors of the Gynecologic Tract

We tested 417 cases of formalin-fixed, paraffin-embedded normal or hyperplastic gynecologic tissues as well as neoplasms involving the gynecologic tract with a monoclonal antibody against CD10 (clone 56C6), with special emphasis on epithelial and epithelial-like structures and tumors. CD10 was always expressed in mesonephric remnants (mesonephric remnants of the uterine cervix, epoophoron, rete ovarii) and tumors (mesonephric adenocarcinoma of the uterine cervix, tumors of wolffian origin of the broad ligament and ovary). CD10 was also positive in the syncytiotrophoblast, cytotrophoblast, and intermediate trophoblast of normal gestations, partial and complete moles, choriocarcinoma, and placental site trophoblastic tumors. Finally, CD10 was positive in several metastatic neoplasms to the gynecologic tract (100% in metastatic renal clear cell and intestinal carcinomas and melanomas). In contrast, CD10 was almost invariably negative in müllerian epithelia of the female genital tract and in their corresponding tumors, with the exception of focal expression found in squamous epithelia and tumors with squamous differentiation. Thus, the expression of CD10 may be useful in the establishing the diagnosis of mesonephric and trophoblastic tumors and in the differential diagnosis between gynecologic clear cell carcinoma (always negative) and metastatic clear cell carcinoma of renal origin.