Nuestros investigadores

Marta Abengozar Muela

Publicaciones científicas más recientes (desde 2010)

Autores: Elgendy, M.; Segura, Victoriano; et al.
ISSN 0020-7136  Vol. 145  Nº 7  2019  págs. 1991 - 2001
Sunitinib is one of the most widely used targeted therapeutics for renal cell-cancer (RCC) but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in renal cell-cancer (RCC), we sequenced the exons of 409 tumor-suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and following development of acquired resistance to sunitinib. From newly arising mutations, we selected, using in-silico prediction models, 6 predicted to be deleterious, located in G6PD, LRP1B, SETD2, TET2, SYNE1 and DCC. Consistently, immunoblotting analysis of lysates derived from sunitinib-desensitized RCC cells and their parental counterparts showed marked differences in the levels and expression pattern of the proteins encoded by these genes. Our further analysis demonstrates essential roles for these proteins in mediating sunitinib cytotoxicity and shows that their loss of function render tumor cells resistant to sunitinib in vitro and in vivo. Finally, sunitinib resistance induced by continuous exposure or by inhibition of the 6 proteins was overcome by treatment with cabozantinib or a low-dose combination of lenvatinib and everolimus. Collectively, our results unravel novel markers of acquired resistance to sunitinib and clinically relevant approaches for overcoming this resistance in RCC.
Autores: Lozano, María D; Abengozar, Marta; Echeveste, José Ignacio; et al.
ISSN 1934-662X  Vol. 127  Nº 7  2019  págs. 470 - 480
Background Programmed death-ligand 1 (PD-L1) expression, as assessed by immunohistochemistry (IHC), is used to select patients with non-small cell lung cancer (NSCLC) for anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy. The current study evaluated the feasibility and efficacy of PD-L1 immunostaining and quantitation on direct Papanicolaou-stained cytological smears compared with formalin-fixed paraffin-embedded samples (cytological cell blocks and surgical resection specimens) in NSCLC cases using 2 commercially available assays: the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies/Dako, Carpinteria, CA, USA) and the Ventana SP263 Assay (Ventana Medical Systems Inc, Tucson, Arizona). Methods PD-L1 immunostaining using either both or one of the assays was tested in 117 sets of paired samples obtained from 62 NSCLC cases. The tumor proportion score was reported in every case following the recommendations of the International Association for the Study of Lung Cancer (IASLC). Results In 57 sets of samples, both PD-L1 assays were used. Due to the availability of samples, only 1 assay was performed in 3 sets of samples and in 2 cases, only cytology smears were used and tested for both assays. A total of 113 sets of paired samples finally were evaluated; 4 cases could not be studied due to intense nonspecific background staining. A significant concordance between the 2 assays on cytological smears was found. Concordance between paired cytological smears and formalin-fixed paraffin-embedded samples was observed in 97.3% of the cases. Conclusions The quantification of PD-L1 expression on direct Papanicolaou-stained cytology smears is feasible and reliable for both PD-L1 assays.
Autores: de Andrea, CE; Abengozar, Marta; Garcia-Ros, D; et al.
ISSN 0023-6837  Vol. 99  Nº Supl. 1  2019 
Autores: Lozano, María D; Echeveste, José Ignacio; Abengozar, Marta; et al.
ISSN 0003-9985  Vol. 142  Nº 3  2018  págs. 291 - 298
CONTEXT: - The rapid advances in targeted therapies in non-small cell lung cancer (NSCLC) make the optimization and implementation of cytology specimens for molecular testing a priority. Up to 70% of patients with NSCLC are diagnosed at advanced stages and tissue biopsies often cannot be taken. Although cytology samples provide high-quality material for molecular testing, molecular cytopathology is not yet well known or widely used. OBJECTIVE: - To report the many advances in molecular cytopathology and the suitability and utility of cytology samples in molecular and genetic testing of NSCLC. DATA SOURCES: - Data sources comprised published peer-reviewed literature and personal experience of the authors. CONCLUSIONS: - Molecular testing can be performed on cytologic specimens, especially on direct smears. Rapid on-site evaluation by cytopathologists has improved the adequacy and the management of cytology samples for molecular testing. Mutational profiling of NSCLC using next-generation sequencing can be performed on cytology samples from very small amounts of DNA. Fluorescence in situ hybridization assays on cytology specimens, including stained direct smear, offer some distinct advantages over their histologic counterpart, and are used to detect ALK and ROS1 rearrangements in NSCLC. Cytology specimens allow assessment of the entire tumor cell nucleus, avoiding signal loss from truncation artifacts. The use of cytology samples for assessing programmed death ligand-1 protein expression is currently being developed. Protocols for bisulfite conversion and DNA droplet digital polymerase chain reaction assays have been optimized for cytology smear to investigate aberrant DNA methylation of several NSCLC-related genes
Autores: Lozano, María D; Abengozar, Marta; et al.
ISSN 0893-3952  Vol. 31  Nº Supl. 2  2018  págs. 158
Autores: de Andrea, CE; Abengozar, Marta; Mejías, Luis Daniel; et al.
ISSN 0893-3952  Vol. 31  Nº Supl. 2  2018  págs. 158 - 158
Autores: Fernandez, L.; Arean, C.; Panizo, A.; et al.
ISSN 0931-0509  Vol. 33  Nº Supl.1  2018  págs. 399 - 400
Autores: Idoate, Miguel Ángel; Mejías, Luis Daniel; Abengozar, Marta; et al.
ISSN 0893-3952  Vol. 31  Nº Supl. 2  2018  págs. 74 - 74
Autores: Lozano, María D; Aguirre, María Mercedes; et al.
ISSN 1556-0864  Vol. 12  Nº 1  2017  págs. S519 - S520
Autores: Lozano, María D; Mejías, Luis Daniel; Abengozar, Marta; et al.
ISSN 1556-0864  Vol. 12  Nº 1  2017  págs. S503 - S503
Autores: Abengozar, Marta; Fernández-Aceñero MJ; Chaves S; et al.
ISSN 0344-0338  Vol. 208  Nº 4  2012  págs. 235-9
In a recent report, tumor thickness at the tumor-normal interface (TNI) was confirmed as a prognosticator for patients with hepatic metastases from colorectal carcinoma after adjuvant chemotherapy. We retrospectively reviewed the hepatectomy specimens with metastasis from colonic adenocarcinoma in a single tertiary hospital. Only 23 patients could be included in this study. Following the recommendations by Maru et al., two independent pathologists, blinded to the outcome of the patients, measured the tumor thickness at the TNI in hematoxylin-eosin stained representative slides of the hepatectomy specimens. The outcome was estimated as the time elapsed between hepatectomy and death due to disease (disease-specific survival; DSS). Two patients showed a complete pathological response, 16 cases a major response, and 5 cases a minor pathological response. The mean thickness at the TNI was 0.73mm (0.01-2.5). The ROC analysis defined a cut-off point of 1.34mm best discriminated between patients with a good and a poor prognosis. The mean thickness at the TNI for patients dying of disease was 1.99 (1.06 for survivors). A comparison of the survival curves confirmed that thickness at the TNI was a significant predictor of disease-free survival (p=0.025). This study demonstrates the value of tumor thickness and TNI in predicting disease-free survival. These results are consistent with previous studies demonstrating that thickness of TNI is an important prognostic variable following hepat
Autores: Fernández-Aceñero, MJ; Abengozar, Marta; Chaves Portela, S; et al.
ISSN 2039-7275  Vol. 11  Nº 3  2011  págs. e44
We have reviewed the electronic biopsies database files of the Department of Surgical Pathology, Fundación Jiménez Díaz in Madrid (Spain). In this time period (1998-2010) we have found 3 pancreatic metastasis and 5 splenic metastasis. Two of the pancreatic metastases were originated in clear cell renal cell carcinomas. The last pancreatic metastasis was from a malignant cutaneous melanoma diagnosed and treated 8 years before. As for splenic metastasis, three of them were diagnosed during the abdominal surgery for primary therapy of the tumour (2 ovaries and one endometrium), while the remaining 2 corresponded to metastasis from a lung primary diagnosed 1 year before and a colonic primary diagnosed 6 years before. The patients with splenic metastasis died on the short term with progression of the disease despite resection of the splenic lesions, while the patients with pancreatic metastasis have survived longer.