RESUMO
Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape of USC by whole-exome sequencing of 57 cancers, most of which were matched to normal DNA from the same patients. The distribution of the number of protein-altering somatic mutations revealed that 52 USC tumors had fewer than 100 (median 36), whereas 5 had more than 3,000 somatic mutations. The mutations in these latter tumors showed hallmarks of defects in DNA mismatch repair. Among the remainder, we found a significantly increased burden of mutation in 14 genes. In addition to well-known cancer genes (i.e., TP53, PIK3CA, PPP2R1A, KRAS, FBXW7), there were frequent mutations in CHD4/Mi2b, a member of the NuRD-chromatin-remodeling complex, and TAF1, an element of the core TFIID transcriptional machinery. Additionally, somatic copy-number variation was found to play an important role in USC, with 13 copy-number gains and 12 copy-number losses that occurred more often than expected by chance. In addition to loss of TP53, we found frequent deletion of a small segment of chromosome 19 containing MBD3, also a member of the NuRD-chromatin-modification complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (an upstream activator of PIK3CA), and CCNE1 (a target of FBXW7-mediated ubiquitination). These findings identify frequent mutation of DNA damage, chromatin remodeling, cell cycle, and cell proliferation pathways in USC and suggest potential targets for treatment of this lethal variant of endometrial cancer.
Assuntos
Variações do Número de Cópias de DNA , Mutação , Neoplasias Uterinas/genética , Sequência de Aminoácidos , Animais , Pareamento Incorreto de Bases , Feminino , Humanos , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
OBJECTIVE: To evaluate c-erbB2 gene amplification in a series of primary uterine serous carcinoma (USC) cell lines. To assess the efficacy of AZD8055, a novel dual mTORC1/2 inhibitor against primary HER2/neu amplified vs HER2/neu not amplified USC cell lines. METHODS: Twenty-two primary USC cell lines were evaluated for c-erbB2 oncogene amplification by FISH assays. In vitro sensitivity to AZD8055 was evaluated by flow-cytometry-based viability and proliferation assays. Cell cycle profile and downstream cellular responses to AZD8055 were assessed by measuring the DNA content of cells and by phosphorylation of the S6 protein by flow-cytometry. RESULTS: Nine of 22 (40.9%) USC cell lines demonstrated c-erbB2 gene amplification by FISH. AZD8055 caused a strong differential growth inhibition in USC cell lines, with high HER-2/neu-expressors demonstrating significantly higher sensitivity when compared to low HER-2/neu-expressors (AZD-8055 IC50 mean±SEM=0.27±0.05µM in c-erbB2 amplified versus 1.67±0.68µM in c-erbB2 not amplified tumors, P=0.03). AZD8055 growth-inhibition was associated with a significant and dose-dependent increase in the percentage of cells blocked in the G0/G1 cell cycle phase and a dose-dependent decline in pS6 levels in both c-erbB2 amplified vs c-erbB2 not amplified USC cell lines. CONCLUSIONS: AZD8055 may represent a novel targeted therapeutic agent in patients harboring advanced/recurrent/refractory USC. c-erbB2 gene amplification may represent a biomarker to identify USC patients who may benefit most from the use of AZD8055.
Assuntos
Carcinoma Papilar/tratamento farmacológico , Cistadenocarcinoma Seroso/tratamento farmacológico , Morfolinas/farmacologia , Receptor ErbB-2/genética , Neoplasias Uterinas/tratamento farmacológico , Antineoplásicos/farmacologia , Carcinoma Papilar/enzimologia , Carcinoma Papilar/genética , Linhagem Celular Tumoral , Cistadenocarcinoma Seroso/enzimologia , Cistadenocarcinoma Seroso/genética , Feminino , Amplificação de Genes , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Complexos Multiproteicos/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias Uterinas/enzimologia , Neoplasias Uterinas/genéticaRESUMO
OBJECTIVE: To compare the in vitro sensitivity/resistance to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas (CS). METHODS: Five primary carcinosarcoma cell lines, two from uterine and three of ovarian origin, were evaluated for growth rate and tested for their in vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays. To identify potential mechanisms underlying the differential sensitivity/resistance to patupilone, expression levels of ß-tubulin III (TUBB3) were determined with quantitative-real-time-polymerase-chain-reaction (q-RT-PCR) in primary uterine and ovarian CS cell lines and in 26 uterine and 9 ovarian CS fresh-frozen-tissues. RESULTS: No appreciable difference in sensitivity to patupilone versus paclitaxel was noted in ovarian CS cell lines, or when uterine and ovarian CS cell lines were compared in their response to paclitaxel. In contrast, uterine CS cell lines were found to be significantly more sensitive to patupilone than to paclitaxel (P<0.002) and demostrated lower IC(50s) to patupilone (range 0.76-0.93nM) when compared to ovarian CS (range 1.9-3.4 nM, p<0.05). Higher levels of TUBB3 were detected in uterine CS cell lines and fresh frozen tissues when compared to ovarian CS (P<0.05). CONCLUSIONS: Uterine CS cell lines are significantly more sensitive than ovarian CS cell lines to patupilone versus paclitaxel. High expression of TUBB3 is associated with sensitivity to patupilone in primary CS cell lines and may act as a genetic marker to predict chemotherapy efficacy. Patupilone may represent a promising drug in the treatment of this subset of rare but highly aggressive gynecological tumors.
Assuntos
Antineoplásicos/uso terapêutico , Carcinossarcoma/tratamento farmacológico , Epotilonas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Tubulina (Proteína)/metabolismo , Neoplasias Uterinas/tratamento farmacológico , Idoso , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Carcinossarcoma/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Epotilonas/farmacologia , Feminino , Humanos , Concentração Inibidora 50 , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Uterinas/metabolismoRESUMO
Carcinosarcomas of the female genital tract are rare tumors with an aggressive clinical behavior. Trastuzumab, a humanized monoclonal antibody, acts by binding to HER2/neu extracellular domain and exhibits therapeutic efficacy in HER2/neu-overexpressing cancers. Two uterine carcinosarcomas (UMMT-ARK-1, UMMT-ARK-2) and 2 ovarian carcinosarcomas (OMMT-ARK-1, OMMT-ARK-2) were established as primary tumor cell lines in vitro and evaluated for HER2/neu expression by immunohistochemistry, fluorescent in situ hybridization analysis, quantitative real-time polymerase chain reaction, and for membrane-bound complement regulatory proteins CD46, CD55, and CD59 by flow cytometry. Sensitivity to trastuzumab-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was studied in 5-hr chromium release assays. HER2/neu expression was demonstrated in OMMT-ARK-1 and OMMT-ARK-2. OMMT-ARK-2 demonstrated an amplification of the c-erbB2 gene by fluorescent in situ hybridization analysis and a high sensitivity to ADCC (mean killing, 45.6%; range, 32.3%-72.6%). A lower level of killing was detected against the fluorescent in situ hybridization analysis-negative OMMT-ARK-1 cell line (mean, 26.5%; range, 21.0%-31.8%). CD46, CD55, and CD59 membrane-bound complement regulatory proteins were expressed at high levels in all primary mixed müllerian tumor cell lines, and all these tumors were found to be highly resistant to complement-dependent cytotoxicity with or without trastuzumab. Addition of untreated and heat-inactivated plasma did not significantly decrease ADCC against OMMT-ARK-2 cell line, suggesting that while the cell line is highly resistant to complement, irrelevant IgG does not significantly alter the ability of trastuzumab to mediate ADCC. Our results suggest that HER2/neu may represent a novel target for the immunotherapy of a subset of human carcinosarcomas refractory to salvage chemotherapy.
Assuntos
Carcinossarcoma/terapia , Imunoterapia , Neoplasias Ovarianas/terapia , Receptor ErbB-2/metabolismo , Neoplasias Uterinas/terapia , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD55/metabolismo , Antígenos CD59/metabolismo , Carcinossarcoma/metabolismo , Carcinossarcoma/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Técnicas In Vitro , Proteína Cofatora de Membrana/metabolismo , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Trastuzumab , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: To determine current practice and to assess the value of routine follow-up procedures for endometrial cancer surveillance. To discuss whether such procedures are feasible and effective to identify asymptomatic recurrences and describe the pattern of relapse detected by procedures. METHODS: The records of 282 consecutive women with recurrent endometrial cancer treated from 1986 to 2005 were retrospectively collected in 8 Italian institutions. Primary disease, clinical history, and recurrence features and data were analyzed. RESULTS: Thirty-five (12.4%) of 282 patients had recurrence in vaginal vault, 51 patients (18.0%) had recurrence in central pelvis, 14 patients (4.9%) had recurrence in pelvic wall, and 39 patients (13.8%) had recurrence in lymph nodes. One-hundred twenty-eight patients (45.3%) showed a distant relapse, whereas 15 patients (5.3%) developed both distant relapse and local relapse. The site of relapse influenced survival because the patients with vaginal vault recurrences lived significantly longer than the patients with recurrences in other sites. Eighty (28.4%) of the 282 patients became symptomatic and anticipated the scheduled visit, 37 (13.1 %) of the patients reported their symptoms during the follow-up meeting, and 165 (58.5 %) of the patients were asymptomatic and the diagnostic path was introduced by a planned visit or examination. Among the asymptomatic patients, the first procedure that led to further examinations was clinical visit alone for 60 (36.4%) of 165 patients, imaging for 103 patients (62.4%), and cytologic examination for 2 patients (1.2%). Symptoms at recurrence can predict survival: patients with an asymptomatic recurrence had a median survival time from relapse of 35 months versus 13 months if they had a symptomatic repetition (P = 0.0001). CONCLUSIONS: Follow-up after endometrial cancer treatment varies in Italy. In this retrospective study, women with asymptomatic recurrence have shown a better clinical outcome compared with those with symptomatic relapse. The optimal approach is actually unknown, and guidelines comparing follow-up protocols have not been established. Prospective cost-effectiveness studies are needed.
Assuntos
Carcinoma/diagnóstico , Neoplasias do Endométrio/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/epidemiologia , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Cervical cancer continues to be an important worldwide health problem for women. Up to 35% of patients who are diagnosed with and appropriately treated for cervical cancer will recur and treatment results are poor for recurrent disease. Given these sobering statistics, development of novel therapies for cervical cancer remains a high priority. We evaluated the expression of Tissue Factor (TF) in cervical cancer and the potential of hI-con1, an antibody-like-molecule targeted against TF, as a novel form of immunotherapy against multiple primary cervical carcinoma cell lines with squamous- and adenocarcinoma histology. METHODS: Because TF is a transmembrane receptor for coagulation factor VII/VIIa (fVII), in this study we evaluated the in vitro expression of TF in cervical carcinoma cell lines by immunohistochemistry (IHC), real time-PCR (qRT-PCR) and flow cytometry. Sensitivity to hI-con1-dependent cell-mediated-cytotoxicity (IDCC) was evaluated in 5-hrs-51chromium-release-assays against cervical cancer cell lines in vitro. RESULTS: Cytoplasmic and/or membrane TF expression was observed in 8 out of 8 (100%) of the tumor tissues tested by IHC and in 100% (11 out of 11) of the cervical carcinoma cell lines tested by real-time-PCR and flow cytometry but not in normal cervical keratinocytes (p=0.0023 qRT-PCR; p=0.0042 flow cytometry). All primary cervical cancer cell lines tested overexpressing TF, regardless of their histology, were highly sensitive to IDCC (mean killing±SD, 56.2%±15.9%, range, 32.4%-76.9%, p<0.001), while negligible cytotoxicity was seen in the absence of hI-con1 or in the presence of rituximab-control-antibody. Low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (p=0.025) while human serum did not significantly decrease IDCC against cervical cancer cell lines (p=0.597). CONCLUSIONS: TF is highly expressed in squamous and adenocarcinoma of the uterine cervix. hI-con1 induces strong cytotoxicity against primary cervical cancer cell lines overexpressing TF and may represent a novel therapeutic agent for the treatment of cervical cancer refractory to standard treatment modalities.
Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Imunoconjugados/uso terapêutico , Imunoterapia , Proteínas de Neoplasias/biossíntese , Tromboplastina/biossíntese , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Proteínas do Sistema Complemento/farmacologia , Testes Imunológicos de Citotoxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Imunoconjugados/farmacologia , Imunoglobulina G/farmacologia , Interleucina-2/farmacologia , Queratinócitos/metabolismo , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Neovascularização Patológica/tratamento farmacológico , Infecções por Papillomavirus/virologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Tromboplastina/antagonistas & inibidores , Tromboplastina/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
OBJECTIVE: We evaluated the expression of human trophoblast cell-surface marker (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a therapeutic agent against chemotherapy-resistant ovarian disease. METHODS: Trop-2 expression was evaluated by immunohistochemistry (IHC) in 50 ovarian serous papillary carcinoma specimens. Trop-2 expression was also evaluated by real-time PCR (qRT-PCR) and flow cytometry in a total of 6 primary ovarian cancer cell lines derived from patients with chemotherapy-resistant disease. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) was tested in standard 5-hour 5¹Cr-release assays. The effect of serum and interleukin-2 (IL-2) on hRS7-mediated ADCC was also studied. RESULTS: Trop-2 expression was found in 41 of 50 (82%) tumor tissues tested by IHC. 83% (5 of 6) of the ovarian cancer cell lines tested by qRT-PCR and flow cytometry demonstrated high Trop-2 expression. All primary ovarian cancer cell lines expressing Trop-2 were highly sensitive to hRS7-mediated ADCC in vitro (range of killing: 19.3% to 40.8%) (p<0.001). Negligible cytotoxicity against chemotherapy-resistant ovarian cancers was seen in the absence of hRS7 or in the presence of rituximab control antibody (range of killing: 1.1% to 8.9%). Human serum did not significantly inhibit hRS7-mediated cytotoxicity while incubation with IL-2 in addition to hRS7 further increased the cytotoxic activity (p=0.04). CONCLUSIONS: Trop-2 is highly expressed in chemotherapy-resistant ovarian cancer cell lines at mRNA and protein levels. Primary ovarian carcinoma cell lines are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for the treatment of high-grade, chemotherapy-resistant ovarian cancer.
Assuntos
Anticorpos Monoclonais/farmacologia , Antígenos de Neoplasias/biossíntese , Moléculas de Adesão Celular/biossíntese , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Anticorpos Monoclonais/imunologia , Citotoxicidade Celular Dependente de Anticorpos , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina G/sangue , Imuno-Histoquímica , Interleucina-2/imunologia , Interleucina-2/farmacologia , Células Matadoras Naturais/imunologia , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genéticaRESUMO
OBJECTIVE: Uterine serous papillary carcinoma (USPC) is an aggressive variant of endometrial cancer characterized by an innate resistance to chemotherapy and poor prognosis. In this study, we evaluated the expression of αV-integrins in primary USPC cell lines and the in vitro ability of intetumumab (CNTO 95), a fully human monoclonal antibody against αV-integrins, to inhibit USPC cell adhesion and migration. MATERIALS AND METHODS: The surface expression of integrins belonging to the αV-family, including αVß3, αVß5, and αVß6, was evaluated in 6 primary USPC cell lines using flow cytometry analysis. To test the ability of intetumumab to inhibit USPC cell adhesion and migration, adhesion assays in the presence of vitronectin and migration assays through an 8.0-µm pore polycarbonate membrane also were performed. RESULTS: We found high expression of the αV-subunit on the cell surface of all 6 primary USPC cell lines tested (100% positive cells; mean fluorescence intensity range, 13.1-39.5). When the expression of single heterodimeric integrins was evaluated, αVß3, αVß5, and αVß6 were expressed on 37.5%, 32.0%, and 16.3% of cells (mean fluorescence intensity range, 6.5-16.2, 9.2-32.5, and 6.2-11.5, respectively). Importantly, in functional assays, low doses of intetumumab were effective in inhibiting adhesion (0.15 µg/mL, P = 0.003) and migration (1.25 µg/mL P = 0.02) of primary USPC cell lines. CONCLUSIONS: The αV-integrins are overexpressed on the cell surface of primary USPC cell lines. Intetumumab may significantly inhibit USPC cell adhesion and migration pathways and may therefore represent a novel treatment option for patients harboring this rare but highly aggressive variant of endometrial cancer.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Integrina alfaV/metabolismo , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/metabolismo , Idoso , Anticorpos Monoclonais Humanizados , Linhagem Celular Tumoral/metabolismo , Cistadenocarcinoma Papilar/tratamento farmacológico , Cistadenocarcinoma Papilar/metabolismo , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Feminino , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Neoplasias Uterinas/patologiaRESUMO
We evaluated the expression of tissue factor (TF) in ovarian cancer (EOC) and the potential of hI-con1, an antibody-like molecule targeting TF, as a novel form of therapy against chemotherapy-resistant ovarian disease. We studied the expression of TF in 88 EOC by immunohistochemistry (IHC) and real-time-PCR (qRT-PCR) and the levels of membrane-bound-complement-regulatory-proteins CD46, CD55 and CD59 in primary EOC cell lines by flow-cytometry. Sensitivity to hI-con1-dependent-cell-mediated-cytotoxicity (IDCC), complement-dependent-cell-cytotoxicity and inhibition of IDCC by γ-immunoglobulin were evaluated in 5-h (51)chromium-release-assays. Cytoplasmic and/or membrane TF expression was observed in 24 out of 25 (96%) of the EOC samples tested by IHC, but not in normal ovarian-tissue. EOC with clear cell histology significantly overexpress TF when compared to serous, endometrioid, or undifferentiated tumors by qRT-PCR. With a single exception, all primary EOC that overexpressed TF demonstrated high levels of CD46, CD55 and CD59 and regardless of their histology or resistance to chemotherapy, were highly sensitive to IDCC. The effect of complement and physiologic doses of γ-immunoglobulin on IDCC in ovarian cancer cell lines overexpressing TF was tumor specific and related to the overexpression of CD59 on tumor cells. Small-interfering-RNA-mediated knockdown of CD59 expression in ovarian tumors significantly increased hI-con1-mediated cytotoxic activity in vitro. Finally, low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (P < 0.01). hI-con1 molecule induces strong cytotoxicity against primary chemotherapy-resistant ovarian cancer cell lines overexpressing TF and may represent a novel therapeutic agent for the treatment of ovarian tumors refractory to standard treatment modalities.
Assuntos
Regulação Neoplásica da Expressão Gênica , Imunoconjugados/uso terapêutico , Imunoterapia/métodos , Neoplasias Ovarianas/tratamento farmacológico , Tromboplastina/uso terapêutico , Linhagem Celular Tumoral , Fator VII/imunologia , Fator VII/metabolismo , Fator VII/uso terapêutico , Feminino , Humanos , Imunoconjugados/imunologia , Imunoconjugados/metabolismo , Fragmentos Fc das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/metabolismo , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Tromboplastina/genética , Tromboplastina/imunologia , Tromboplastina/metabolismoRESUMO
BACKGROUND: We evaluated the expression of human trophoblastic cell-surface marker (Trop-2) and the potential of hRS7 - a humanized monoclonal anti-Trop-2 antibody - as a therapeutic strategy against treatment-refractory human uterine (UMMT) and ovarian (OMMT) carcinosarcoma cell lines. MATERIALS AND METHODS: Trop-2 expression was evaluated by immunohistochemistry (IHC) in paraffin-embedded tumor tissues, by real-time polymerase-chain-reaction (RT-PCR) and flow-cytometry in cell lines. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested using 5-hour chromium-release assays against UMMT and OMMT cells. RESULTS: Trop-2 expression was elevated in 9 of 26 (35%) UMMT and 8 of 14 (57%) OMMT tissues tested by IHC. Positivity for Trop-2 mRNA by RT-PCR and surface expression by flow cytometry were detected in 2 of 4 cell lines, with high positivity noted in OMMT-ARK-2. OMMT-ARK-2 was highly sensitive to hRS7 ADCC (range: 34.7-41.0%; P < 0.001) with negligible cytotoxicity seen in the absence of hRS7 or in the presence of control antibody (range: 1.1-2.5%). Human IgG did not significantly inhibit ADCC while human complement increased, hRS7-mediated-cytotoxicity against OMMT-ARK-2. CONCLUSION: Trop-2 is overexpressed in a proportion of UMMT and OMMT, and hRS7 may represent a novel, potentially highly effective treatment option for patients with treatment-refractory carcinosarcomas overexpressing Trop-2.