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Cristina Perez-Sanchez,
Eva Colas, Silvia Cabrera,
Orlando Falcon,
Angel Sanchez-Del-Río,
Enrique García,
Luis Fernández-de-Castillo,
Juan Carlos Muruzabal,
Elena Alvarez,
Gabriel Fiol, [......],
Carlos Nieto,
Alicia Ortega,
Nuria Pedrola,
Marta Llauradó,
Marina Rigau,
Andreas Doll,
Miguel Abal,
Jordi Ponce,
Antonio Gil-Moreno,
Jaume Reventós
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ABSTRACT: Rapid and reliable diagnosis of endometrial cancer (EC) in uterine aspirates is highly desirable. Current sensitivity and failure rate of histological diagnosis limit the success of this method and subsequent hysteroscopy is often necessary. Using qRT-PCR on RNA from uterine aspirates samples, we measured the expression level of 20 previously identified genes involved in EC pathology, created five algorithms based on combinations of 5 genes and evaluated their ability to diagnose EC. The algorithms were tested in a double-blind, prospective, multicenter study. We enlisted 514 patients who presented with abnormal uterine bleeding. EC was diagnosed in 60 of the 514 patients (12%). Molecular analysis was performed on the remnants of aspirates and results were compared to the final histological diagnoses obtained through biopsies acquired by aspiration or guided by hysteroscopy, or from the specimens resected by hysterectomy. Algorithm 5 was the best performing molecular diagnostic classifier in the case-control and validation study. The molecular test had a sensitivity of 81%, specificity of 96%, positive predictive value (PPV) of 75% and negative predictive value (NPV) of 97%. A combination of the molecular and histological diagnosis had a sensitivity of 91%, specificity of 97%, PPV of 79% and NPV of 99% and the cases that could be diagnosed on uterine aspirate rose from 76% to 93% when combined with the molecular test. Incorporation of the molecular diagnosis increases the reliability of a negative diagnosis, reduces the need for hysteroscopies, and helps to identify additional cases. © 2013 Wiley Periodicals, Inc.
International Journal of Cancer 05/2013; · 5.44 Impact Factor
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Eva Colas,
Nuria Pedrola,
Laura Devis,
Tugçe Ertekin,
Irene Campoy,
Elena Martínez,
Marta Llauradó,
Marina Rigau,
Mireia Olivan,
Marta Garcia, [......],
Santiago Ramon Y Cajal,
Gema Moreno-Bueno,
Xavier Dolcet,
Francesc Alameda,
Jose Palacios,
Jaime Prat,
Andreas Doll,
Xavier Matias-Guiu,
Miguel Abal,
Jaume Reventos
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ABSTRACT: Endometrial cancer (EC) is the most common gynecologic malignancy of the female genital tract and the fourth most common neoplasia in women. In EC, myometrial invasion is considered one of the most important prognostic factors. For this process to occur, epithelial tumor cells need to undergo an epithelial to mesenchymal transition (EMT), either transiently or stably, and to differing degrees. This process has been extensively described in other types of cancer but has been poorly studied in EC. In this review, several features of EMT and the main molecular pathways responsible for triggering this process are investigated in relation to EC. The most common hallmarks of EMT have been found in EC, either at the level of E-cadherin loss or at the induction of its repressors, as well as other molecular alterations consistent with the mesenchymal phenotype-like L1CAM and BMI-1 up-regulation. Pathways including progesterone receptor, TGFβ, ETV5 and microRNAs are deeply related to the EMT process in EC.
Clinical and Translational Oncology 08/2012; 14(10):715-20. · 1.33 Impact Factor
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Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 05/2012; 55(5):1496. · 3.52 Impact Factor
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Silvia Cabrera,
Marta Llauradó,
Josep Castellví,
Yolanda Fernandez,
Francesc Alameda,
Eva Colás,
Anna Ruiz,
Andreas Doll,
Simó Schwartz,
Ramon Carreras,
Jordi Xercavins,
Miguel Abal,
Antonio Gil-Moreno,
Jaume Reventós
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ABSTRACT: We describe the generation of two orthotopic murine models for endometrial cancer (EC).The first model is generated from endometrial Hec-1A cancer cells transfected with luciferase and injected directly into the uterus of female mice. This model allows a follow-up with bioluminescence imaging (BLI) along the experiment and generates abdominal dissemination and lymphatic and hematogenous metastases in high percentages, also detectables with BLI. The dissemination pattern of this model imitates the advanced stages of EC in patients, and its molecular profile corresponds to aggressive type 2 EC (p53 positive, hormone receptors negative, high percentage of Ki67 positive cells). The second model is derived from endometrioid human tissue collected from surgical pieces. By injecting this tissue inside the uterine cavity of a mouse we obtain orthotopic growth with pelvic dissemination and lymph node metastasis. The molecular pattern observed in human type 1 endometrioid EC (p53 negative, low Ki67 index, presence of hormone receptors) is conserved after the murine growth in orthotopic tumor and metastases. This model supposes a singular pre-clinical tool to study therapeutic agents, though it mimics clinical and molecular behavior of endometrioid EC, which is the most common histology in the patient.
Clinical and Experimental Metastasis 12/2011; 29(3):217-27. · 3.52 Impact Factor
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ABSTRACT: To assess the safety, feasibility, and impact on survival of extraperitoneal para-aortic lymphadenectomy in the staging of patients with bulky or locally advanced cervical cancer.
Between August 2001 and October 2009, 87 consecutive patients (median age 5 years) with bulky or locally advanced cervical cancer underwent extraperitoneal laparoscopic infrarenal aortic and common iliac dissection as a pretherapeutic staging procedure. Data on pathologic findings, details of surgery, postoperative complications, and disease status at follow-up were collected.
The median operating time was 150 min (range 60-255 min). The mean (± standard deviation) para-aortic nodal yield was 15.5 ± 8.1 (range 4-62). In none of the patients, conversion to the transperitoneal approach or laparotomy was necessary. Histological examination revealed metastasis in 13 patients (macroscopic disease 10, microscopic disease 3). After a median follow-up of 33.4 months (range 13.3-65.9 months), 73.6% of patients were free of disease and 1.1% were alive with disease, 19.5% died from cervical cancer, and 3.3% died from other causes. After a follow-up of 3 years, no deaths or recurrences were documented, with an overall survival rate of 74.8% (95% CI 62.8%-83.4%) and disease-free survival of 86% (95% CI 74.7%-92.5%). There were no significant differences in overall survival and disease-free survival between patients with positive and negative para-aortic lymph nodes.
The extraperitoneal laparoscopic para-aortic lymphadenectomy for pretherapeutic surgical staging in cervical cancer is a safe and feasible procedure that should be considered as a tool to identify lymph node positive patients who require extended-field radiation and/or chemotherapy.
Annals of Surgical Oncology 02/2011; 18(2):482-9. · 4.17 Impact Factor
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Eva Colas,
Cristina Perez, Silvia Cabrera,
Nuria Pedrola,
Marta Monge,
Josep Castellvi,
Fernando Eyzaguirre,
Jesus Gregorio,
Anna Ruiz,
Marta Llaurado, [......],
Rafael Lopez-Lopez,
Ramon Carreras,
Jordi Xercavins,
Alicia Ortega,
Tamara Maes,
Elisabet Rosell,
Andreas Doll,
Miguel Abal,
Jaume Reventos,
Antonio Gil-Moreno
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ABSTRACT: Endometrial cancer (EC) is the most frequent of the invasive tumors of the female genital tract. Although usually detected in its initial stages, a 20% of the patients present with advanced disease. To date, no characterized molecular marker has been validated for the diagnosis of EC. In addition, new methods for prognosis and classification of EC are needed to combat this deadly disease. We thus aimed to identify new molecular markers of EC and to evaluate their validity on endometrial aspirates. Gene expression screening on 52 carcinoma samples and series of real-time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and noncarcinoma uterine aspirates were performed to identify and validate potential biomarkers of EC. Candidate markers were further confirmed at the protein level by immunohistochemistry and Western blot. We identified ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2 and DCN as differentially expressed in ECs. Furthermore, the differential expression of these biomarkers in primary endometrial tumors is correlated to their expression level in corresponding uterine fluid samples. Finally, these biomarkers significantly identified EC with area under the receiver-operating-characteristic values ranging from 0.74 to 0.95 in uterine aspirates. Interestingly, analogous values were found among initial stages. We present the discovery of molecular biomarkers of EC and describe their utility in uterine aspirates. These findings represent the basis for the development of a highly sensitive and specific minimally invasive method for screening ECs.
International Journal of Cancer 01/2011; 129(10):2435-44. · 5.44 Impact Factor
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Gynecologic Oncology 12/2010; 121(3):639; author reply 639-40. · 3.89 Impact Factor
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Annals of Surgical Oncology 12/2010; · 4.17 Impact Factor
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ABSTRACT: To estimate the safety and feasibility of extraperitoneal laparoscopic approach for the diagnosis and treatment of paraaortic lymph node recurrence in gynecologic cancers.
Between December 2002 and September 2009, 15 patients underwent extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected isolated lymph node recurrence in the Gynecologic Oncology Unit of Hospital Vall d'Hebron. The suspected diagnosis of recurrence was performed with computed tomography scanning, 18F-fluorodeoxyglucose positron emission tomography scanning, or magnetic resonance imaging.
The median age of patients was 63 years (range 42-75). The median body mass index was 28.5 Kg/m(2) (range 18-38). The median operative time was 157.5 minutes (range 120-240). The median blood loss was 70 mL (range 30-150). The mean nodal yield was 7.7 +/- 5.3 (range 1-16). The median hospital stay was 2 days (range 2-13). There was 1 conversion to laparotomy. There was only 1 postoperative complication, a lymphorrhea that was resolved with drainage. Recurrence was confirmed in the pathologic study in 13 of the 15 patients.
The extraperitoneal laparoscopic surgical approach is a feasible and safe procedure for the diagnosis of paraaortic lymph node recurrences of gynecologic cancers. The previous abdominal surgeries or treatment with chemotherapy or radiotherapy and high body mass index are not a problem. The low complication rate, low blood loss and low hospitalization allow a rapid recovery of the patients, which in turn, allows the rapid onset of adjuvant therapy. Complete debulking of suspicious lymphadenopathy offers an exact diagnosis of malignancy, and it may have a therapeutic benefit in the case of being positive.
Journal of Minimally Invasive Gynecology 17(5):570-5. · 1.74 Impact Factor
