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Ross S. Berkowitz - One of the best experts on this subject based on the ideXlab platform.
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placental site Trophoblastic Tumors and epithelioid Trophoblastic Tumors biology natural history and treatment modalities
Gynecologic Oncology, 2017Co-Authors: Neil S Horowitz, Donald P. Goldstein, Ross S. BerkowitzAbstract:Placental site (PSTT) and epithelioid Trophoblastic Tumor (ETT) are rare types of gestational Trophoblastic neoplasia (GTN) that arise from intermediate trophoblast. Given that this cell of origin is different from other forms of GTN, it is not surprising that the clinical presentation, Tumor marker profile, and treatment paradigm for PSTT and ETT are quite different as well. The mainstay for therapy for stage I PSTT and ETT is hysterectomy with adjuvant chemotherapy reserved for those presenting greater than four years from the antecedent pregnancy. Surgery is also important for metastatic disease. There is no standardized chemotherapy regimen for advanced stage disease but often consists of a platinum-containing combination therapy, usually EMA-EP or TE/TP. Despite its rarity, PSTT and ETT account for a disproportionate percentage of mortality from GTN likely resulting from their relative chemotherapy resistance. Novel therapeutic modalities therefore are needed to improve the outcomes of women with advanced stage or resistant PSTT and ETT.
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epithelioid Trophoblastic Tumor a single institution case series at the new england Trophoblastic disease center
Gynecologic Oncology, 2015Co-Authors: Michelle Davis, Ross S. Berkowitz, Donald P. Goldstein, Brooke E Howitt, Bradley J Quade, Christopher P Crum, Neil S HorowitzAbstract:Abstract Objective Epithelioid Trophoblastic Tumor (ETT) is a rare form of gestational Trophoblastic neoplasm which is distinct based on its development from intermediate trophoblast cells and nodular growth pattern. The aim of this study is to describe a case series from a single institution with a review of the literature to better understand the clinical characteristics and outcomes for patients with ETT. Methods A retrospective review was performed using the IRB approved New England Trophoblastic Disease Center (NETDC) database from 1998 to 2014. Eight patients were identified of which seven had complete records. Follow-up data was obtained from the longitudinal medical records. Results Four (57.1%) patients presented with vaginal bleeding and two (28.6%) patients were asymptomatic at presentation. Three (42.9%) patients had extrauterine disease. All three patients with extrauterine disease who received chemotherapy had stable or progressive disease at follow-up. Only two (29%) patients who presented with non-metastatic disease and underwent hysterectomy were alive with no evidence of disease. The mean interval following antecedent pregnancy was 104months. All patients with an interval >4years demonstrated stable or progressive disease despite intensive chemotherapy. Two patients with non-metastatic disease who declined hysterectomy developed stable or progressive disease despite chemotherapy. Conclusions This series highlights several features of ETT including the potential for asymptomatic presentation of extrauterine disease. The series also demonstrates chemoresistance, even with multi-agent therapy and a poor prognosis with extrauterine disease and an interval greater than 4years following the antecedent pregnancy suggesting that surgery remains critical in disease control.
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diagnosis classification and treatment of gestational Trophoblastic neoplasia
Revista Brasileira de Ginecologia e Obstetrícia, 2015Co-Authors: Andressa Biscaro, Antonio Braga, Ross S. BerkowitzAbstract:Gestational Trophoblastic neoplasia (GTN) is the term to describe a set of malignant placental diseases, including invasive mole, choriocarcinoma, placental site Trophoblastic Tumor and epithelioid Trophoblastic Tumor. Both invasive mole and choriocarcinoma respond well to chemotherapy, and cure rates are greater than 90%. Since the advent of chemotherapy, low-risk GTN has been treated with a single agent, usually methotrexate or actinomycin D. Cases of high-risk GTN, however, should be treated with multiagent chemotherapy, and the regimen usually selected is EMA-CO, which combines etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine. This study reviews the literature about GTN to discuss current knowledge about its diagnosis and treatment.
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placental site Trophoblastic Tumor a 17 year experience at the new england Trophoblastic disease center
Obstetrical & Gynecological Survey, 2002Co-Authors: Colleen M Feltmate, Donald P. Goldstein, David R Genest, Lauren A Wise, Marilyn R Bernstein, Ross S. BerkowitzAbstract:Sixteen patients with recurrent placental site Trophoblastic Tumor were identified in the cancer registry of the New England Trophoblastic Disease Center for the years 1982 to 1999. Three patients were excluded when theirdiagnosis was changed to exaggerated placental site reaction in a review of the pathology report. This article presents the results of an investigation of the records of the 13 remaining patients. The mean age of study subjects at the time of diagnosis was 31 years, and mean gravidity was 2.2. Antecedent gestational events included seven full-term pregnancies (53.8%), two spontaneous abortions, three therapeutic abortions, and one molar pregnancy. Only one patient was diagnosed because of persistent β-human chorionic gonadotropin (β-hCG) elevation. The remaining 12 presented with irregular bleeding or amenorrhea. The time from the antecedent gestational event to diagnosis ranged from 2 weeks to 5 years (mean, 16.5 months). One woman had a serum β-hCG level of 2000 mIU/ml at the time of diagnosis, but the remaining 12 patients had β-hCG levels below 500 mIU/ml. Diagnosis was made by endometrial curettage in 12 of the 13 patients and by hysterectomy in 1 patient. Four patients had pelvic metastases at the time of diagnosis. Average follow-up was 56 months. All of the women underwent hysterectomy (one after failed treatment with uterine resection and chemotherapy). In the week after surgery, one patient, who presented with metastases and was receiving chemotherapy, developed septic shock (unrelated to myelosuppression) and died. She was excluded from the final analysis. The remaining three patients who presented with metastases and five of the nine other patients were treated with adjuvant chemotherapy. The chemotherapy regimens included various combinations of methotrexate, actinomycin D, cyclophosphamide, etoposide, vincristine, and cisplatin. Two of the three patients with presenting metastases and three patients with no initial metastases had a recurrence (5 of 12, 43%). All five patients with a recurrence had been treated with chemotherapy (5 of 8, 63%). Recurrences were treated with additional chemotherapy, local excision, or both. Mitotic count was the only variable to reach significance in a statistical analysis of possible predictors of Tumor recurrence. Patients with a recurrence had median mitotic counts of 10 mitoses per 10 high-power fields (HPF) compared with median counts of 2 mitoses per 10 HPF for patients who did not have a recurrence (P =.04). No patient with a mitotic count of 5 or fewer mitoses per 10 HPF had a recurrence, and all of those with counts above 5 had a recurrence.
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placental site Trophoblastic Tumor a 17 year experience at the new england Trophoblastic disease center
Gynecologic Oncology, 2001Co-Authors: Colleen M Feltmate, Donald P. Goldstein, David R Genest, Lauren A Wise, Marilyn R Bernstein, Ross S. BerkowitzAbstract:Abstract Objective. We reviewed cases of placental site Trophoblastic Tumors from the New England Trophoblastic Disease Center (NETDC) database from 1982–1999 in an effort to identify prognostic factors for recurrent disease. Methods. A chart review was performed utilizing patients identified from the NETDC database. Data obtained included patient age at diagnosis, antecedent pregnancy, duration and extent of disease, presenting symptoms, pre- and posttreatment hCG levels, diagnostic and therapeutic procedures, treatment and outcome of patients. Statistical analysis was performed using Student's t test and χ 2 test when appropriate. Results. Thirteen patients were identified. All ultimately underwent hysterectomy although initial treatment of 1 patient was uterine resection. There were 5 recurrences (43%)—3 among the 9 patients who had no metastases on presentation (33%) and 2 of 3 patients who presented with metastases (66%). The 5 patients who recurred were among 8 who had received peri- or postoperative chemotherapy (62.5%). Treatment of recurrences included continued or alternate chemotherapy, radiotherapy, and/or excision of locally recurrent disease. Follow up time averaged 56.2 months (range 12–182 months). One of the 4 patients receiving chemotherapy ≤1 week after hysterectomy recurred, whereas all 4 patients who received chemotherapy 3 weeks or more after hysterectomy recurred. Uterine Tumor volume was significantly greater, 154.1 cm 3 , in patients with initial metastases versus 42.3 cm 3 in patients without initial metastases ( P = 0.04). Mitotic index ( P = 0.04) was significantly increased in patients who developed recurrent disease. Conclusion. High mitotic index appears to be an adverse prognostic indicator for recurrence. Hysterectomy remains the mainstay of treatment. Chemotherapy is indicated for patients with metastases and may be indicated when the mitotic index is >5 mitoses/10 HPF. Radiation treatment may play a role in recurrent disease but must be evaluated on a case-by-case basis.
Ie Ming Shih - One of the best experts on this subject based on the ideXlab platform.
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metastatic epithelioid Trophoblastic Tumor in a male patient with mixed germ cell Tumor of the testis
The American Journal of Surgical Pathology, 2009Co-Authors: Robert W Allan, Chester B Algood, Ie Ming ShihAbstract:: This report describes a rare case of a concurrent epithelioid Trophoblastic Tumor (ETT) and a teratoma in a para-aortic lymph node from a 39-year-old male patient with the initial diagnosis of testicular malignant mixed germ-cell Tumor. The metastatic lesion was excised 2 years after orchiectomy and chemotherapy. Microscopically, the metastatic lesion contained a teratoma component and dispersed small nests of cohesive chorionic-type intermediate Trophoblastic cells, closely resembling gestational ETT in female patients. The diagnosis of ETT in this case was confirmed by stepwise immunohistochemistry. Demonstration of ETT as one of the histologic manifestations of recurrent testicular germ-cell Tumors should encourage pathologists to recognize this unique feature in assessing posttreatment mixed germ-cell neoplasm. Furthermore, this case represents a unique opportunity to understand the pathobiology of Trophoblastic neoplasms arising from germ-cell Tumors.
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uterine epithelioid Trophoblastic Tumor in an african green monkey chlorocebus aethiops sabaeus
Journal of The American Association for Laboratory Animal Science, 2007Co-Authors: David K Chu, Ie Ming Shih, Mary Knezevich, Sachiv ShethAbstract:A uterine mass was detected on physical exam in a multiparous African green monkey as an incidental finding, and the well-circumscribed mass was removed via hysterectomy. Histologically, the mass consisted of sheets, nests, and cords of uniform intermediate Trophoblastic cells with eosinophilic or clear cytoplasm. These neoplastic cells aggregated around blood vessels, forming islands of viable Tumor cells amid extensive areas of coagulative necrosis with calcification in a 'geographic' pattern of necrosis. Immunohistochemistry of the Trophoblastic cells revealed strong and diffuse staining for pancytokeratin AE1/3 and p63, with weak and moderate staining for human placental lactogen and placental alkaline phosphatase, respectively. Immunohistochemical staining for smooth muscle actin, epithelial membrane antigen, and human chorionic gonadotropin was negative. Overall, the histologic and immunohistochemical features of this Tumor were consistent with those of epithelioid Trophoblastic Tumor. This rare Tumor type has not been reported previously to occur in African green monkeys.
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hla g immunoreactivity is specific for intermediate trophoblast in gestational Trophoblastic disease and can serve as a useful marker in differential diagnosis
The American Journal of Surgical Pathology, 2002Co-Authors: Gad Singer, Robert J. Kurman, Michael T Mcmaster, Ie Ming ShihAbstract:HLA-G is a nonclassical MHC class I antigen that has been shown to be a specific marker for normal intermediate trophoblast (IT). In this study HLA-G immunoreactivity assessed with an HLA-G specific antibody (4H84) was detected in all 14 cases of choriocarcinoma, 14 placental site Trophoblastic Tumors, 13 epithelioid Trophoblastic Tumors, 16 placental site nodules, and nine exaggerated placental sites. In contrast, HLA-G immunoreactivity was not detected in 34 nonTrophoblastic uterine neoplasms. HLA-G immunoreactivity was present in all the IT cells of exaggerated placental sites and placental site Trophoblastic Tumors and in 70-100% of IT cells in placental site nodules and epithelioid Trophoblastic Tumors. The pattern of distribution of HLA-G in different subpopulations of IT confirms the relationship of various Trophoblastic lesions to different types of IT (exaggerated placental site and placental site Trophoblastic Tumor to implantation site IT and placental site nodule and epithelioid Trophoblastic Tumor to chorionic-type IT) and suggests that choriocarcinoma is related to villous-type IT because the majority of mononucleate cells in this neoplasm were HLA-G immunoreactive. In conclusion, HLA-G immunoreactivity appears to be specific for IT in gestational Trophoblastic disease and can serve as a useful marker in the differential diagnosis of these lesions.
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the pathology of intermediate Trophoblastic Tumors and Tumor like lesions
International Journal of Gynecological Pathology, 2001Co-Authors: Ie Ming Shih, Robert J. KurmanAbstract:An intermediate trophoblast is a distinctive Trophoblastic cell population from which four Trophoblastic lesions are thought to arise: exaggerated placental site (EPS), placental site nodule (PSN), placental site Trophoblastic Tumor (PSTT), and epithelioid Trophoblastic Tumor (ETT). EPSs and PSTTs are related to the differentiation of the intermediate trophoblast in the implantation site (implantation site intermediate trophoblast), whereas PSNs and ETTs are related to the intermediate trophoblast of the chorion laeve (chorionic-type intermediate trophoblast). EPSs and PSNs are nonneoplastic lesions, whereas PSTTs and ETTs are neoplasms with a potential for local invasion and metastasis. Microscopically, intermediate Trophoblastic lesions can be confused with a variety of Trophoblastic and nonTrophoblastic Tumors, but an appreciation of the morphologic features and immunophenotype allows their diagnosis to be relatively straightforward in most instances. Correct diagnosis is important because each of these lesions may require different therapeutic approaches.
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epithelioid Trophoblastic Tumor a neoplasm distinct from choriocarcinoma and placental site Trophoblastic Tumor simulating carcinoma
The American Journal of Surgical Pathology, 1998Co-Authors: Ie Ming Shih, Robert J. KurmanAbstract:This report describes the clinicopathologic and immunohistochemical features of 14 cases of epithelioid Trophoblastic Tumor (ETT), a distinctive but rare gestational Trophoblastic Tumor. The patients with this neoplasm were in the reproductive age group and presented with abnormal vaginal bleeding.
Donald P. Goldstein - One of the best experts on this subject based on the ideXlab platform.
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placental site Trophoblastic Tumors and epithelioid Trophoblastic Tumors biology natural history and treatment modalities
Gynecologic Oncology, 2017Co-Authors: Neil S Horowitz, Donald P. Goldstein, Ross S. BerkowitzAbstract:Placental site (PSTT) and epithelioid Trophoblastic Tumor (ETT) are rare types of gestational Trophoblastic neoplasia (GTN) that arise from intermediate trophoblast. Given that this cell of origin is different from other forms of GTN, it is not surprising that the clinical presentation, Tumor marker profile, and treatment paradigm for PSTT and ETT are quite different as well. The mainstay for therapy for stage I PSTT and ETT is hysterectomy with adjuvant chemotherapy reserved for those presenting greater than four years from the antecedent pregnancy. Surgery is also important for metastatic disease. There is no standardized chemotherapy regimen for advanced stage disease but often consists of a platinum-containing combination therapy, usually EMA-EP or TE/TP. Despite its rarity, PSTT and ETT account for a disproportionate percentage of mortality from GTN likely resulting from their relative chemotherapy resistance. Novel therapeutic modalities therefore are needed to improve the outcomes of women with advanced stage or resistant PSTT and ETT.
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epithelioid Trophoblastic Tumor a single institution case series at the new england Trophoblastic disease center
Gynecologic Oncology, 2015Co-Authors: Michelle Davis, Ross S. Berkowitz, Donald P. Goldstein, Brooke E Howitt, Bradley J Quade, Christopher P Crum, Neil S HorowitzAbstract:Abstract Objective Epithelioid Trophoblastic Tumor (ETT) is a rare form of gestational Trophoblastic neoplasm which is distinct based on its development from intermediate trophoblast cells and nodular growth pattern. The aim of this study is to describe a case series from a single institution with a review of the literature to better understand the clinical characteristics and outcomes for patients with ETT. Methods A retrospective review was performed using the IRB approved New England Trophoblastic Disease Center (NETDC) database from 1998 to 2014. Eight patients were identified of which seven had complete records. Follow-up data was obtained from the longitudinal medical records. Results Four (57.1%) patients presented with vaginal bleeding and two (28.6%) patients were asymptomatic at presentation. Three (42.9%) patients had extrauterine disease. All three patients with extrauterine disease who received chemotherapy had stable or progressive disease at follow-up. Only two (29%) patients who presented with non-metastatic disease and underwent hysterectomy were alive with no evidence of disease. The mean interval following antecedent pregnancy was 104months. All patients with an interval >4years demonstrated stable or progressive disease despite intensive chemotherapy. Two patients with non-metastatic disease who declined hysterectomy developed stable or progressive disease despite chemotherapy. Conclusions This series highlights several features of ETT including the potential for asymptomatic presentation of extrauterine disease. The series also demonstrates chemoresistance, even with multi-agent therapy and a poor prognosis with extrauterine disease and an interval greater than 4years following the antecedent pregnancy suggesting that surgery remains critical in disease control.
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placental site Trophoblastic Tumor a 17 year experience at the new england Trophoblastic disease center
Obstetrical & Gynecological Survey, 2002Co-Authors: Colleen M Feltmate, Donald P. Goldstein, David R Genest, Lauren A Wise, Marilyn R Bernstein, Ross S. BerkowitzAbstract:Sixteen patients with recurrent placental site Trophoblastic Tumor were identified in the cancer registry of the New England Trophoblastic Disease Center for the years 1982 to 1999. Three patients were excluded when theirdiagnosis was changed to exaggerated placental site reaction in a review of the pathology report. This article presents the results of an investigation of the records of the 13 remaining patients. The mean age of study subjects at the time of diagnosis was 31 years, and mean gravidity was 2.2. Antecedent gestational events included seven full-term pregnancies (53.8%), two spontaneous abortions, three therapeutic abortions, and one molar pregnancy. Only one patient was diagnosed because of persistent β-human chorionic gonadotropin (β-hCG) elevation. The remaining 12 presented with irregular bleeding or amenorrhea. The time from the antecedent gestational event to diagnosis ranged from 2 weeks to 5 years (mean, 16.5 months). One woman had a serum β-hCG level of 2000 mIU/ml at the time of diagnosis, but the remaining 12 patients had β-hCG levels below 500 mIU/ml. Diagnosis was made by endometrial curettage in 12 of the 13 patients and by hysterectomy in 1 patient. Four patients had pelvic metastases at the time of diagnosis. Average follow-up was 56 months. All of the women underwent hysterectomy (one after failed treatment with uterine resection and chemotherapy). In the week after surgery, one patient, who presented with metastases and was receiving chemotherapy, developed septic shock (unrelated to myelosuppression) and died. She was excluded from the final analysis. The remaining three patients who presented with metastases and five of the nine other patients were treated with adjuvant chemotherapy. The chemotherapy regimens included various combinations of methotrexate, actinomycin D, cyclophosphamide, etoposide, vincristine, and cisplatin. Two of the three patients with presenting metastases and three patients with no initial metastases had a recurrence (5 of 12, 43%). All five patients with a recurrence had been treated with chemotherapy (5 of 8, 63%). Recurrences were treated with additional chemotherapy, local excision, or both. Mitotic count was the only variable to reach significance in a statistical analysis of possible predictors of Tumor recurrence. Patients with a recurrence had median mitotic counts of 10 mitoses per 10 high-power fields (HPF) compared with median counts of 2 mitoses per 10 HPF for patients who did not have a recurrence (P =.04). No patient with a mitotic count of 5 or fewer mitoses per 10 HPF had a recurrence, and all of those with counts above 5 had a recurrence.
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placental site Trophoblastic Tumor a 17 year experience at the new england Trophoblastic disease center
Gynecologic Oncology, 2001Co-Authors: Colleen M Feltmate, Donald P. Goldstein, David R Genest, Lauren A Wise, Marilyn R Bernstein, Ross S. BerkowitzAbstract:Abstract Objective. We reviewed cases of placental site Trophoblastic Tumors from the New England Trophoblastic Disease Center (NETDC) database from 1982–1999 in an effort to identify prognostic factors for recurrent disease. Methods. A chart review was performed utilizing patients identified from the NETDC database. Data obtained included patient age at diagnosis, antecedent pregnancy, duration and extent of disease, presenting symptoms, pre- and posttreatment hCG levels, diagnostic and therapeutic procedures, treatment and outcome of patients. Statistical analysis was performed using Student's t test and χ 2 test when appropriate. Results. Thirteen patients were identified. All ultimately underwent hysterectomy although initial treatment of 1 patient was uterine resection. There were 5 recurrences (43%)—3 among the 9 patients who had no metastases on presentation (33%) and 2 of 3 patients who presented with metastases (66%). The 5 patients who recurred were among 8 who had received peri- or postoperative chemotherapy (62.5%). Treatment of recurrences included continued or alternate chemotherapy, radiotherapy, and/or excision of locally recurrent disease. Follow up time averaged 56.2 months (range 12–182 months). One of the 4 patients receiving chemotherapy ≤1 week after hysterectomy recurred, whereas all 4 patients who received chemotherapy 3 weeks or more after hysterectomy recurred. Uterine Tumor volume was significantly greater, 154.1 cm 3 , in patients with initial metastases versus 42.3 cm 3 in patients without initial metastases ( P = 0.04). Mitotic index ( P = 0.04) was significantly increased in patients who developed recurrent disease. Conclusion. High mitotic index appears to be an adverse prognostic indicator for recurrence. Hysterectomy remains the mainstay of treatment. Chemotherapy is indicated for patients with metastases and may be indicated when the mitotic index is >5 mitoses/10 HPF. Radiation treatment may play a role in recurrent disease but must be evaluated on a case-by-case basis.
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gestational Trophoblastic disease subsequent pregnancy outcome including repeat molar pregnancy
Journal of Reproductive Medicine, 1998Co-Authors: Ross S. Berkowitz, M R Bernstein, Donald P. GoldsteinAbstract:OBJECTIVE: To determine subsequent reproductive outcomes in patients treated for partial molar pregnancy, complete molar pregnancy and persistent gestational Trophoblastic Tumors at the New England Trophoblastic Disease Center (NETDC) between June 1, 1965, and December 31, 1996. STUDY DESIGN: Questionnaires were mailed to all patients followed at the NETDC to assess subsequent pregnancy experience. All patients and their referring physicians were also requested to inform the NETDC about later pregnancies. RESULTS: Following partial mole, complete mole and persistent gestational Trophoblastic Tumor, our patients had 195, 1,234 and 504 later pregnancies, respectively. These patients had a later pregnancy experience comparable to that of the general population. However, after having one molar pregnancy, the risk of molar pregnancy in a later conception was about 1%. Twenty-nine of our patients had at least two episodes of molar pregnancy; following two episodes of molar pregnancy, 6 (23.1%) of 26 later conceptions resulted in another molar gestation. CONCLUSION: Patients with partial mole, complete mole and persistent gestational Trophoblastic Tumor can be reassured that in general they can anticipate a normal future reproductive outcome.
Annie N Y Cheung - One of the best experts on this subject based on the ideXlab platform.
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placental site Trophoblastic Tumor a distinct entity of gestational Trophoblastic disease experience from a tertiary referral center in hong kong
Journal of Reproductive Medicine, 2016Co-Authors: Mandy M Y Chu, Annie N Y Cheung, Ka Yu Tse, Karen K L Chan, Hextan Y.s. NganAbstract:OBJECTIVE To review the clinical and pathological characteristics of patients with placental site Trophoblastic Tumor (PS TT) managed in a tertiary referral center in Hong Kong. STUDY DESIGN Patients with a diagnosis of PSTT from 1995 to 2012 were identified from a computer database. Clinical and patho- logical data were obtained from medical records and the electronic database. RESULTS Ten patients with PSTT were identified. Only 4 patients (40%) had disease confined to the uterus at presentation (Stage I). The most common site of metastasis was the lung. Four patients had pretreatment serum hCG levels <1,000 IU/L, and all of them had disease 'confined to the uterus. Of the 4 patients with Stage I disease 3 had hysterectomy only and 1 had both hysterectomy and chemotherapy. All 4 patients achieved complete remission; although 1 of them had a recurrence successfully treated with che- motherapy. For patients with Stage III/IV disease most of them had both hysterectomy and chemotherapy. Only 1 patient (20%) was alive without evidence of disease. CONCLUSION Patients with Stage I disease have excellent prognosis after hysterectomy, and adjuvant treatment is not recommended. A low pretreatment serum hCG level (<1,000 IU/L) was a good predictor of early stage disease. The prognosis for patients with metastatic disease was poor despite surgery and com- bination chemotherapy.
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p21 activated kinase 1 promotes aggressive phenotype cell proliferation and invasion in gestational Trophoblastic disease
American Journal of Pathology, 2010Co-Authors: Michelle Ky Siu, Daniel Sh Kong, Hextan Y.s. Ngan, Dominic C.w. Chan, Huijuan Zhang, Matthew C W Yeung, Annie N Y CheungAbstract:Gestational Trophoblastic disease (GTD) includes hydatidiform mole (HM), which can develop persistent gestational Trophoblastic neoplasia requiring chemotherapy; choriocarcinoma, which is a frankly malignant Tumor; placental site Trophoblastic Tumor; and epithelioid Trophoblastic Tumor. p21-Activated kinases (PAKs) promote malignant Tumor progression. Therefore, this study investigated PAK1, PAK2, and p-PAK2 Ser20 in the pathogenesis of GTD. By real-time PCR, PAK1 mRNA was significantly higher in HMs, particularly metastatic HMs (P = 0.046) and HMs that developed persistent disease (P = 0.011), when compared with normal placentas. By immunohistochemistry, significantly increased cytoplasmic PAK1 immunoreactivity in cytotrophoblasts was also detected in HMs (P = 0.042) and choriocarcinomas (P = 0.003). In addition, HMs that developed persistent disease displayed higher PAK1 immunoreactivity than those that regressed (P = 0.016), and elevated PAK1 immunoreactivity was observed in placental site Trophoblastic Tumors. Indeed, there was significant positive correlation between PAK1 expression and the proliferative indices Ki-67 (P = 0.016) and MCM7 (P = 0.026). Moreover, higher PAK1 mRNA and protein expression was confirmed in the choriocarcinoma cell-lines JEG-3 and JAR; however, PAK2 mRNA and p-PAK2 immunoreactivity showed a similar expression pattern in normal first trimester placentas and GTD. Knockdown of PAK1 in JEG-3 and JAR reduced cell proliferation, migration, and invasion ability, up-regulated p16, and down-regulated vascular endothelial growth factor and MT1-MMP expression. This is the first report revealing the involvement of PAK1 in the pathogenesis and clinical progress of GTD.
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coexisting epithelioid Trophoblastic Tumor and choriocarcinoma of the uterus following a chemoresistant hydatidiform mole
Archives of Pathology & Laboratory Medicine, 2009Co-Authors: Danhua Shen, Hextan Y.s. Ngan, Weicheng Xue, U S Khoo, M T Chau, Annie N Y CheungAbstract:Abstract The epithelioid Trophoblastic Tumor is an unusual type of Trophoblastic Tumor. Herein, we describe a patient with coexisting epithelioid Trophoblastic Tumor and choriocarcinoma in the uterus. The patient had a history of hydatidiform mole with recurrent elevation of human chorionic gonadotrophin level that is resistant to chemotherapy. Histopathologic and immunohistochemical examination showed distinctive differences between the 2 Trophoblastic Tumors. The development of epithelioid Trophoblastic Tumor may be related to the persistence of locally invasive disease, which was unresponsive to chemotherapy. The patient responded well to surgery. The presence of an epithelioid Trophoblastic Tumor should be considered in chemoresistant gestational trophoblast Tumor.
Robert J. Kurman - One of the best experts on this subject based on the ideXlab platform.
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hla g immunoreactivity is specific for intermediate trophoblast in gestational Trophoblastic disease and can serve as a useful marker in differential diagnosis
The American Journal of Surgical Pathology, 2002Co-Authors: Gad Singer, Robert J. Kurman, Michael T Mcmaster, Ie Ming ShihAbstract:HLA-G is a nonclassical MHC class I antigen that has been shown to be a specific marker for normal intermediate trophoblast (IT). In this study HLA-G immunoreactivity assessed with an HLA-G specific antibody (4H84) was detected in all 14 cases of choriocarcinoma, 14 placental site Trophoblastic Tumors, 13 epithelioid Trophoblastic Tumors, 16 placental site nodules, and nine exaggerated placental sites. In contrast, HLA-G immunoreactivity was not detected in 34 nonTrophoblastic uterine neoplasms. HLA-G immunoreactivity was present in all the IT cells of exaggerated placental sites and placental site Trophoblastic Tumors and in 70-100% of IT cells in placental site nodules and epithelioid Trophoblastic Tumors. The pattern of distribution of HLA-G in different subpopulations of IT confirms the relationship of various Trophoblastic lesions to different types of IT (exaggerated placental site and placental site Trophoblastic Tumor to implantation site IT and placental site nodule and epithelioid Trophoblastic Tumor to chorionic-type IT) and suggests that choriocarcinoma is related to villous-type IT because the majority of mononucleate cells in this neoplasm were HLA-G immunoreactive. In conclusion, HLA-G immunoreactivity appears to be specific for IT in gestational Trophoblastic disease and can serve as a useful marker in the differential diagnosis of these lesions.
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the pathology of intermediate Trophoblastic Tumors and Tumor like lesions
International Journal of Gynecological Pathology, 2001Co-Authors: Ie Ming Shih, Robert J. KurmanAbstract:An intermediate trophoblast is a distinctive Trophoblastic cell population from which four Trophoblastic lesions are thought to arise: exaggerated placental site (EPS), placental site nodule (PSN), placental site Trophoblastic Tumor (PSTT), and epithelioid Trophoblastic Tumor (ETT). EPSs and PSTTs are related to the differentiation of the intermediate trophoblast in the implantation site (implantation site intermediate trophoblast), whereas PSNs and ETTs are related to the intermediate trophoblast of the chorion laeve (chorionic-type intermediate trophoblast). EPSs and PSNs are nonneoplastic lesions, whereas PSTTs and ETTs are neoplasms with a potential for local invasion and metastasis. Microscopically, intermediate Trophoblastic lesions can be confused with a variety of Trophoblastic and nonTrophoblastic Tumors, but an appreciation of the morphologic features and immunophenotype allows their diagnosis to be relatively straightforward in most instances. Correct diagnosis is important because each of these lesions may require different therapeutic approaches.
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epithelioid Trophoblastic Tumor a neoplasm distinct from choriocarcinoma and placental site Trophoblastic Tumor simulating carcinoma
The American Journal of Surgical Pathology, 1998Co-Authors: Ie Ming Shih, Robert J. KurmanAbstract:This report describes the clinicopathologic and immunohistochemical features of 14 cases of epithelioid Trophoblastic Tumor (ETT), a distinctive but rare gestational Trophoblastic Tumor. The patients with this neoplasm were in the reproductive age group and presented with abnormal vaginal bleeding.
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ki 67 labeling index in the differential diagnosis of exaggerated placental site placental site Trophoblastic Tumor and choriocarcinoma a double immunohistochemical staining technique using ki 67 and mel cam antibodies
Human Pathology, 1998Co-Authors: Ie Ming Shih, Robert J. KurmanAbstract:The diagnosis of placental site Trophoblastic lesions, particularly the distinction of a placental site Trophoblastic Tumor from an exaggerated placental site, can be difficult. Mel-CAM (also known as CD146 and MUC18) is a recently recognized cell adhesion molecule belonging to the immunoglobin gene superfamily that specifically identifies intermediate trophoblast (IT). In this study, we evaluated immunohistochemical staining of Ki-67 (using Mib-1 antibody) in Mel-CAM defined IT as an aid in the differential diagnosis of these lesions. Formalin-fixed tissue samples from 24 normal implantation sites, 19 exaggerated placental sites, five molar implantation sites, 16 placental site Trophoblastic Tumors, and 12 choriocarcinomas were stained with a Mel-CAM-specific polyclonal antibody and a Ki-67 antibody using streptavidin-biotin immunoperoxidase with two different chromagens. No Ki-67 nuclear labeling was seen in IT of normal implantation sites. The Ki-67 index (mean +/- standard deviation) in IT of exaggerated placental site was near zero, but in the molar implantation sites the Ki-67 index was 5.2% +/- 4.0%. In contrast, the Ki-67 index in IT of placental site Trophoblastic Tumor was 14% +/- 6.9% and in choriocarcinoma was 69% +/- 20%. The differences in the Ki-67 labeling index were statistically significant (P < .001) between exaggerated placental site, placental site Trophoblastic Tumor, and choriocarcinoma. In conclusion, a double-staining technique using MIB-1 antibody to determine the Ki-67 proliferative index in Mel-CAM defined IT is a useful technique in the differential diagnosis of exaggerated placental site versus placental site Trophoblastic Tumor and placental site Trophoblastic Tumor versus choriocarcinoma.
