Search

Your search keyword '"Bague S"' showing total 28 results
Start Over Author "Bague S"
28 results on '"Bague S"'

8. Somatic PIK3CA mutations as a driver of sporadic venous malformations

Author

Castel, P, Carmona, FJ, Grego-Bessa, J, Berger, MF, Viale, A, Anderson, KV, Bague, S, Scaltriti, M, Antonescu, CR, Baselga, E, and Baselga, J

Abstract

Venous malformations (VM) are vascular malformations characterized by enlarged and distorted blood vessel channels. VM grow over time and cause substantial morbidity because of disfigurement, bleeding, and pain, representing a clinical challenge in the absence of effective treatments (Nguyen et al., 2014; Uebelhoer et al., 2012). Somatic mutations may act as drivers of these lesions, as suggested by the identification of TEK mutations in a proportion of VM(Limaye et al., 2009). We report that activating PIK3CA mutations gives rise to sporadic VM in mice, which closely resemble the histology of the human disease. Furthermore, we identified mutations in PIK3CA and related genes of the PI3K (phosphatidylinositol 3-kinase)/AKT pathway in about 30% of human VM that lack TEK alterations. PIK3CA mutations promote downstream signaling and proliferation in endothelial cells and impair normal vasculogenesis in embryonic development. We successfully treated VM in mouse models using pharmacological inhibitors of PI3K alpha administered either systemically or topically. This study elucidates the etiology of a proportion of VM and proposes a therapeutic approach for this disease.

Published
2016

9. Differences between en bloc resection and enucleation of retroperitoneal sarcomas

Author

Lopez, JAG, Raventos, VA, Blanco, MR, Lopez-Pousa, A, Bague, S, Abellan, M, and Folch, MT

Subjects
Multidisciplinary management, Retroperitoneal sarcoma, En bloc resection
Abstract

Aim: Today, free margin surgery is the gold-standard management for soft-tissue sarcoma patients and one of the most important predictors of recurrence and survival. To obtain optimal results, a multidisciplinary approach is necessary. The aim of this study was to evaluate the evolution of patients with RPS treated by "en bloc" surgical resection versus those treated with enucleation in the first surgery. Methods: Fifty-six adult patients were divided into 2 groups. Patients in Group A underwent enucleation surgery, and patients in Group B underwent en bloc surgery. The endpoints of the study were survival time and time to recurrence, according to histological type and first surgical strategy. Results: Disease-free survival was longer for en bloc surgery (P

Published
2014

10. BRAF V600E and KRAS G12S mutations in peripheral nerve sheath tumours

Author

Serrano, C, Simonetti, S, Hernandez-Losa, J, Valverde, C, Carrato, C, Bague, S, Orellana, R, Somoza, R, Moline, T, Carles, J, Huguet, P, Romagosa, C, and Cajal, SRY

Subjects
acoustic neuroma, neurofibromatosis type 2, NF1, NF2, KRAS, malignant peripheral nerve sheath tumour, neurofibromatosis type 1, schwannoma, BRAF, neurofibroma
Abstract

Aims Benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumours occur either sporadically or are related to neurofibromatosis (NF). The mechanisms involved are well known in NF-related tumours, but still remain unclear in sporadic cases. Somatic BRAF and KRAS mutations represent the most frequent genetic events in melanocytic neoplastic lesions. Because melanocytes and Schwann cells both derive from neural crest cells, we hypothesized that BRAF and KRAS mutations might influence BPNST and MPNST development. Methods and results BRAF exon 15 and KRAS exons 2 and 3 polymerase chain reaction (PCR) sequencing was performed in formalin-fixed/paraffin-embedded samples of 99 BPNST and MPNST, related and non-related to NF types 1 and 2. Oncogenic BRAF V600E mutations were found in four of 40 schwannomas (including one acoustic neuroma) and one of 13 MPNST, not associated with NF. A KRAS G12S mutation was also evident in one sporadic schwannoma. Conclusion Our findings suggest that RAS pathway activation due to BRAF V600E and KRAS mutations is an important event in a subset of peripheral nerve sheath tumours not related to NF.

Published
2013

11. Role of tumor-associated macrophages and angiogenesis in desmoid-type fibromatosis

Author

Romero S., Szafranska J., Cabrera E., Gonzalez A., Peiró A., Llauger J., Ortega L., Bague S., Canet B., Espinosa I., and Prat J.

Subjects
Adult, Male, Adolescent, Genotype, review, recurrence free survival, tumor associated leukocyte, Kaplan-Meier Estimate, Polymerase Chain Reaction, angiogenesis, Young Adult, CD163 antigen, Humans, gene mutation, human, macrophage function, beta Catenin, Aged, CD31 antigen, Aged, 80 and over, density, Neovascularization, Pathologic, human cell, Macrophages, Middle Aged, Prognosis, major clinical study, Immunohistochemistry, human tissue, Fibromatosis, Aggressive, female, priority journal, Tissue Array Analysis, fibromatosis, microvasculature
Abstract

Desmoid-type fibromatosis (DTF) is a rare soft tissue tumor with fibroblastic features affecting two to four individuals per million population per year. Despite its bland microscopic appearance, the tumor behaves aggressively. Although unable to metastasize, DTF tends to recur and local recurrences in anatomically critical sites can be fatal. Tumor-associated macrophages (TAM) play an important role in tumor development through the activation of angiogenesis, particularly in cases of epithelial malignancies. The aim of this study is to investigate the prognostic significance of TAMs and the number of microvessels in DTF. Tumor macrophages (CD163), microvessel density (CD31), and beta-catenin were investigated on 69 primary DTF cases with follow-up information. CTNNB1 mutations were also studied. High density of tumor macrophages and high number of microvessels were associated with a significantly worse recurrence-free survival (P=0.03 and P=0.007, respectively). There was a significant correlation between microvessel density and CD163 macrophages (P=0.02). Furthermore, combination of high number of tumor macrophages and high microvessel density greatly improved the statistical significance (P=0.000005). Macrophages and microvessels may play an important role in the biologic behavior of DTF. This finding could help in the clinical management of patients with DTF. © Springer-Verlag 2012.

Published
2012

14. 1505P - Analysis of expression of immunomodulation factors in alveolar soft-part sarcoma: a retrospective study from the Spanish Group for Research on Sarcoma (GEIS)

Author

Hindi, N., Fernandez-Serra, A., Martinez-Trufero, J., Carranza-Carranza, A., Lopez-Pousa, A., Lavernia, J., Arranz, J.L., López Alegret, R., Martinez-Garcia, J., Valverde Morales, C., Cano, J.M., Vaz, M.A., Moura, D.S., Bagué, S., Gonzalez-Campora, R., Lopez-Guerrero, J.A., and Martin-Broto, J.

Published
2017
Full Text
View/download PDF

15. MEDICAL AND NEURO-ONCOLOGY

Author

Prithviraj, G. K., primary, Sommers, S. R., additional, Jump, R. L., additional, Halmos, B., additional, Chambless, L. B., additional, Parker, S. L., additional, Hassam-Malani, L., additional, McGirt, M. J., additional, Thompson, R. C., additional, Hunter, K., additional, Chamberlain, M. C., additional, Le, E. M., additional, Lee, E. L. T., additional, Sadighi, Z. S., additional, Pearlman, M. L., additional, Slopis, J. M., additional, Vats, T. S., additional, Khatua, S., additional, DeVito, N. C., additional, Yu, M., additional, Chen, R., additional, Pan, E., additional, Cloughesy, T., additional, Raizer, J., additional, Drappatz, J., additional, Gerena-Lewis, M., additional, Rogerio, J., additional, Yacoub, S., additional, Desjardin, A., additional, Groves, M. D., additional, DeGroot, J., additional, Loghin, M., additional, Conrad, C. A., additional, Hess, K., additional, Ni, J., additional, Ictech, S., additional, Yung, W. A., additional, Porter, A. B., additional, Dueck, A. C., additional, Karlin, N. J., additional, Olson, J., additional, Silber, J., additional, Reiner, A. S., additional, Panageas, K. S., additional, Iwamoto, F. M., additional, Cloughesy, T. F., additional, Aldape, K. D., additional, Rivera, A. L., additional, Eichler, A. F., additional, Louis, D. N., additional, Paleologos, N. A., additional, Fisher, B. J., additional, Ashby, L. S., additional, Cairncross, J. G., additional, Roldan, G. B., additional, Wen, P. Y., additional, Ligon, K. L., additional, Shiff, D., additional, Robins, H. I., additional, Rocque, B. G., additional, Mason, W. P., additional, Weaver, S. A., additional, Green, R. M., additional, Kamar, F. G., additional, Abrey, L. E., additional, DeAngelis, L. M., additional, Jhanwar, S. C., additional, Rosenblum, M. K., additional, Lassman, A. B., additional, Cachia, D., additional, Alderson, L., additional, Moser, R., additional, Smith, T., additional, Yunus, S., additional, Saito, K., additional, Mukasa, A., additional, Narita, Y., additional, Tabei, Y., additional, Shinoura, N., additional, Shibui, S., additional, Saito, N., additional, Flechl, B., additional, Ackerl, M., additional, Sax, C., additional, Dieckmann, K., additional, Crevenna, R., additional, Widhalm, G., additional, Preusser, M., additional, Marosi, C., additional, Ay, C., additional, Dunkler, D., additional, Pabinger, I., additional, Zielinski, C., additional, Belongia, M., additional, Jogal, S., additional, Schlingensiepen, K.-H., additional, Bogdahn, U., additional, Stockhammer, G., additional, Mahapatra, A. K., additional, Venkataramana, N. K., additional, Oliushine, V., additional, Parfenov, V., additional, Poverennova, I., additional, Hau, P., additional, Jachimczak, P., additional, Heinrichs, H., additional, Mammoser, A. G., additional, Shonka, N. A., additional, de Groot, J. F., additional, Shibahara, I., additional, Sonoda, Y., additional, Kumabe, T., additional, Saito, R., additional, Kanamori, M., additional, Yamashita, Y., additional, Watanabe, M., additional, Ishioka, C., additional, Tominaga, T., additional, Silvani, A., additional, Gaviani, P., additional, Lamperti, E., additional, Botturi, A., additional, DiMeco, F., additional, Broggi, G., additional, Fariselli, L., additional, Solero, C. L., additional, Salmaggi, A., additional, Woyshner, E. A., additional, Shu, F., additional, Oh, Y. S., additional, Iganej, S., additional, Singh, G., additional, Vemuri, S. L., additional, Theeler, B. J., additional, Ellezam, B., additional, Gilbert, M. R., additional, Aoki, T., additional, Kobayashi, H., additional, Takano, S., additional, Nishikawa, R., additional, Nagane, M., additional, Muragaki, Y., additional, Sugiyama, K., additional, Kuratsu, J., additional, Matsutani, M., additional, Langford, L. A., additional, Puduvalli, V. K., additional, Shen, D., additional, Chen, Z.-p., additional, Zhang, J.-p., additional, Bedekar, D., additional, Rand, S., additional, Connelly, J., additional, Malkin, M., additional, Paulson, E., additional, Mueller, W., additional, Schmainda, K., additional, Gallego, O., additional, Benavides, M., additional, Segura, P. P., additional, Balana, C., additional, Gil, M., additional, Berrocal, A., additional, Reynes, G., additional, Garcia, J. L., additional, Murata, P., additional, Bague, S., additional, Quintana, M. J., additional, Vasishta, V. G., additional, Kobayashi, K., additional, Tanaka, M., additional, Tsuchiya, K., additional, Shiokawa, Y., additional, Bavle, A. A., additional, Ayyanar, K., additional, Prado, M. P., additional, Hess, K. R., additional, Liu, V., additional, de Groot, J., additional, Loghin, M. E., additional, Colman, H., additional, Levin, V. A., additional, Alfred Yung, W. K., additional, Hackney, J. R., additional, Palmer, C. A., additional, Markert, J. M., additional, Cure, J., additional, Riley, K. O., additional, Fathallah-Shaykh, H., additional, Nabors, L. B., additional, Saria, M. G., additional, Corle, C., additional, Hu, J., additional, Rudnick, J., additional, Phuphanich, S., additional, Mrugala, M. M., additional, Lee, L. K., additional, Fu, B. D., additional, Bota, D. A., additional, Kim, R. Y., additional, Brown, T., additional, Feely, H., additional, Hu, A., additional, Lee, J. W., additional, Carter, B., additional, Kesari, S., additional, Kong, X.-T., additional, Sparagana, S., additional, Belousova, E., additional, Jozwiak, S., additional, Korf, B., additional, Frost, M., additional, Kuperman, R., additional, Kohrman, M., additional, Witt, O., additional, Wu, J., additional, Flamini, R., additional, Jansen, A., additional, Curtalolo, P., additional, Thiele, E., additional, Whittemore, V., additional, De Vries, P., additional, Ford, J., additional, Shah, G., additional, Cauwel, H., additional, Edrich, P., additional, Sahmoud, T., additional, Franz, D., additional, Khasraw, M., additional, Brown, C., additional, Ashley, D. M., additional, Rosenthal, M. A., additional, Jiang, X., additional, Mou, Y. g., additional, Chen, Z. p., additional, Oh, M., additional, kim, E., additional, Chang, J., additional, Juratli, T. A., additional, Kirsch, M., additional, Schackert, G., additional, Krex, D., additional, Wang, M., additional, Stupp, R., additional, Hegi, M., additional, Jaeckle, K. A., additional, Armstrong, T. S., additional, Wefel, J. S., additional, Won, M., additional, Blumenthal, D. T., additional, Mahajan, A., additional, Schultz, C. J., additional, Erridge, S. C., additional, Brown, P. D., additional, Chakravarti, A., additional, Curran, W. J., additional, Mehta, M. P., additional, Hofland, K. F., additional, Hansen, S., additional, Sorensen, M., additional, Schultz, H., additional, Muhic, A., additional, Engelholm, S., additional, Ask, A., additional, Kristiansen, C., additional, Thomsen, C., additional, Poulsen, H. S., additional, Lassen, U. N., additional, Zalatimo, O., additional, Weston, C., additional, Zoccoli, C., additional, Glantz, M., additional, Rahmanuddin, S., additional, Shiroishi, M. S., additional, Cen, S. Y., additional, Jones, J., additional, Chen, T., additional, Pagnini, P., additional, Go, J., additional, Lerner, A., additional, Gomez, J., additional, Law, M., additional, Ram, Z., additional, Wong, E. T., additional, Gutin, P. H., additional, Bobola, M. S., additional, Alnoor, M., additional, Silbergeld, D. L., additional, Rostomily, R. C., additional, Silber, J. R., additional, Martha, N., additional, Jacqueline, S., additional, Thaddaus, G., additional, Daniel, P., additional, Hans, M., additional, Armin, M., additional, Eugen, T., additional, Gunther, S., additional, Hutterer, M., additional, Tseng, H.-M., additional, Zoccoli, C. M., additional, Patel, A., additional, Rizzo, K., additional, Sheehan, J. M., additional, Sumrall, A. L., additional, Vredenburgh, J. J., additional, Desjardins, A., additional, Reardon, D. A., additional, Friiedman, H. S., additional, Peters, K. B., additional, Taylor, L. P., additional, Stewart, M., additional, Blondin, N. A., additional, Baehring, J. M., additional, Foote, T., additional, Laack, N., additional, Call, J., additional, Hamilton, M. G., additional, Walling, S., additional, Eliasziw, M., additional, Easaw, J., additional, Shirsat, N. V., additional, Kundar, R., additional, Gokhale, A., additional, Goel, A., additional, Moiyadi, A. A., additional, Wang, J., additional, Mutlu, E., additional, Oyan, A., additional, Yan, T., additional, Tsinkalovsky, O., additional, Jacobsen, H. K., additional, Talasila, K. M., additional, Sleire, L., additional, Pettersen, K., additional, Miletic, H., additional, Andersen, S., additional, Mitra, S., additional, Weissman, I., additional, Li, X., additional, Kalland, K.-H., additional, Enger, P. O., additional, Sepulveda, J., additional, Belda, C., additional, Sitt, R., additional, Phishniak, L., additional, Bokstein, F., additional, Philippe, M., additional, Carole, C., additional, Andre, M. d. P., additional, Marylin, B., additional, Olivier, C., additional, L'Houcine, O., additional, Dominique, F.-B., additional, Isabelle, N.-M., additional, Frederic, F., additional, Stephane, F., additional, Henry, D., additional, Errico, M. A., additional, Kunschner, L. J., additional, Soffietti, R., additional, Trevisan, E., additional, Ruda, R., additional, Bertero, L., additional, Bosa, C., additional, Fabrini, M. G., additional, Lolli, I., additional, Jalali, R., additional, Julka, P. K., additional, Anand, A. K., additional, Bhavsar, D., additional, Singhal, N., additional, Naik, R., additional, John, S., additional, Mathew, B. S., additional, Thaipisuttikul, I., additional, Graber, J., additional, Shirinian, M., additional, Fontebasso, A. M., additional, Jacob, K., additional, Gerges, N., additional, Montpetit, A., additional, Nantel, A., additional, Albrecht, S., additional, Jabado, N., additional, Shah, K., additional, Di, K., additional, Linskey, M., additional, Thon, N., additional, Eigenbrod, S., additional, Kreth, S., additional, Lutz, J., additional, Tonn, J.-C., additional, Kretzschmar, H., additional, Peraud, A., additional, Kreth, F.-W., additional, Muggeri, A. D., additional, Alderuccio, J. P., additional, Diez, B. D., additional, Jiang, P., additional, Chao, Y., additional, Gallagher, M., additional, Kim, R., additional, Pastorino, S., additional, Fogal, V., additional, Rudnick, J. D., additional, Bresee, C., additional, Rogatko, A., additional, Sakowsky, S., additional, Franco, M., additional, Lim, S., additional, Lopez, A., additional, Yu, L., additional, Ryback, K., additional, Tsang, V., additional, Lill, M., additional, Steinberg, A., additional, Sheth, R., additional, Grimm, S., additional, Helenowski, I., additional, Rademaker, A., additional, Nunes, F. P., additional, Merker, V., additional, Jennings, D., additional, Caruso, P., additional, Muzikansky, A., additional, Stemmer-Rachamimov, A., additional, Plotkin, S., additional, Spalding, A. C., additional, Vitaz, T. W., additional, Sun, D. A., additional, Parsons, S., additional, Welch, M. R., additional, Omuro, A., additional, Beal, K., additional, Correa, D., additional, Chan, T., additional, DeAngelis, L., additional, Gavrilovic, I., additional, Nolan, C., additional, Hormigo, A., additional, Kaley, T., additional, Mellinghoff, I., additional, Grommes, C., additional, Panageas, K., additional, Reiner, A., additional, Barradas, R., additional, Abrey, L., additional, Gutin, P., additional, Lee, S. Y., additional, Slagle-Webb, B., additional, Glantz, M. J., additional, Connor, J. R., additional, Schlimper, C. A., additional, Schlag, H., additional, Stoffels, G., additional, Weber, F., additional, Krueger, D. A., additional, Care, M. M., additional, Holland, K., additional, Agricola, K., additional, Tudor, C., additional, Byars, A., additional, Franz, D. N., additional, Rice, L., additional, Chandler, J., additional, Levy, R., additional, Muro, K., additional, Nayak, L., additional, Norden, A. D., additional, Kaley, T. J., additional, Thomas, A. A., additional, Fadul, C. E., additional, Meyer, L. P., additional, Lallana, E. C., additional, Gilbert, M., additional, Aldape, K., additional, De Groot, J., additional, Conrad, C., additional, Levin, V., additional, Groves, M., additional, Chris, P., additional, Puduvalli, V., additional, Nagpal, S., additional, Feroze, A., additional, Recht, L., additional, Rangarajan, H. G., additional, Kieran, M. W., additional, Scott, R. M., additional, Lew, S. M., additional, Firat, S. Y., additional, Segura, A. D., additional, Jogal, S. A., additional, Kumthekar, P. U., additional, Grimm, S. A., additional, Avram, M., additional, Patel, J., additional, Kaklamani, V., additional, McCarthy, K., additional, Cianfrocca, M., additional, Gradishar, W., additional, Mulcahy, M., additional, Von Roenn, J., additional, Galanis, E., additional, Anderson, S. K., additional, Lafky, J. M., additional, Kaufmann, T. J., additional, Uhm, J. H., additional, Giannini, C., additional, Kumar, S. K., additional, Northfelt, D. W., additional, Flynn, P. J., additional, Buckner, J. C., additional, Omar, A. I., additional, Schiff, D., additional, Delios, A., additional, Jakubowski, A., additional, Melguizo-Gavilanes, I., additional, Qiao, W., additional, Wang, X., additional, Hashemi-Sadraei, N., additional, Bawa, H., additional, Rahmathulla, G., additional, Patel, M., additional, Elson, P., additional, Stevens, G., additional, Peereboom, D., additional, Vogelbaum, M., additional, Weil, R., additional, Barnett, G., additional, Ahluwalia, M. S., additional, Alvord, E. C., additional, Rockne, R. C., additional, Rockhill, J. K., additional, Rostomily, R., additional, Lai, A., additional, Wardlaw, J., additional, Spence, A. M., additional, Swanson, K. R., additional, Zadeh, G., additional, Alahmadi, H., additional, Wilson, J., additional, Gentili, F., additional, Beumer, J. J., additional, Wright, J., additional, Takebe, N., additional, Gaur, R., additional, Werner-Wasik, M., additional, Gupta, A. J., additional, Campos-Gines, A., additional, Le, K., additional, Arango, C., additional, Richards, M., additional, Landeros, M., additional, Juan, H., additional, Chang, J. H., additional, Kim, J. S., additional, Cho, J. H., additional, Seo, C. O., additional, Baldock, A. L., additional, Rockne, R., additional, Canoll, P., additional, Born, D., additional, Yagle, K., additional, Alexandru, D., additional, Bota, D., additional, Linskey, M. E., additional, Nabeel, S., additional, Raval, S. N., additional, Rosenow, J., additional, Bredel, M., additional, New, P. Z., additional, Plotkin, S. R., additional, Supko, J. G., additional, Curry, W. T., additional, Chi, A. S., additional, Gerstner, E. R., additional, Batchelor, T. T., additional, Hashemi, N., additional, Chao, S. T., additional, Weil, R. J., additional, Suh, J. H., additional, Vogelbaum, M. A., additional, Stevens, G. H., additional, Barnett, G. H., additional, Corwin, D., additional, Holdsworth, C., additional, Stewart, R., additional, Swanson, K., additional, Graber, J. J., additional, Anderson, A. R., additional, Jeyapalan, S., additional, Goldman, M., additional, Boxerman, J., additional, Donahue, J., additional, Elinzano, H., additional, Evans, D., additional, O'Connor, B., additional, Puthawala, M. Y., additional, Oyelese, A., additional, Cielo, D., additional, Blitstein, M., additional, Dargush, M., additional, Santaniello, A., additional, Constantinou, M., additional, DiPetrillo, T., additional, Safran, H., additional, Halpin, C., additional, Barker, F. G., additional, Maher, E. A., additional, Ganji, S., additional, DeBerardinis, R., additional, Hatanpaa, K., additional, Rakheja, D., additional, Yang, X.-L., additional, Mashimo, T., additional, Raisanen, J., additional, Madden, C., additional, Mickey, B., additional, Malloy, C., additional, Bachoo, R., additional, Choi, C., additional, Ranjan, T., additional, Yono, N., additional, Han, S. J., additional, Sun, M., additional, Berger, M. S., additional, Aghi, M., additional, Gupta, N., additional, and Parsa, A. T., additional

Published
2011
Full Text
View/download PDF

18. 227P - Prognosis of Phosphorylated-Insulin Growth Factor Receptor (P-Igf-1R) and Metalloproteinase-3 (Mmp3) Expression in Advanced Gastrointestinal Stromal Tumors (Gist) Patients Treated with Imatinib. a Geis Study

Author

Maurel, J., Lopez-Pousa, A., Calabuig, S., Bagué, S., Del Muro, X. García, Sanjuan, X., Rubió, J., Cuatrecasas, M., Martinez-Trufero, J., Horndler, C., Fra, J., Morales, C. Valverde, Redondo, A., Poveda, A.M., Sevilla, I., Lainez, N., Rubini, M., Albéniz, X. García, Broto, J. Martin, and De Álava, E.

Published
2014
Full Text
View/download PDF

20. Schwannomas, bening tumors with a senescent phenotype

Author

Simonetti, S., Serrano, C., Hernandez-Losa, J., Bague, S., Orellana, R., Valverde, C., Lleonart, M. E., Aizpurua, M., Carles, J., Santiago Ramon y Cajal, and Romagosa, C.

Subjects
p16INK4a, MPNST, 5 - Ciencias puras y naturales::57 - Biología::576 - Biología celular y subcelular. Citología [CDU], Schwannomas, otorhinolaryngologic diseases, Senescence, neoplasms
Abstract

Background: Schwannomas are benign nerve sheath tumors that only very rarely undergo malignant changes. Oncogenic-induced senescence is a defense mechanism against such malignant transformation. Different molecular pathways are involved in this process, such as RAS-RAF-MAPK. Based on the fact that the RAS-RAF-MAPK pathway is known to be activated in peripheral nerve sheath tumors, this study analyzes senescence markers in Schwannomas to demonstrate the possible role of senescence in their genesis. Methods: A retrospective immunohistochemical study was done in 39 schwannoma and 18 malignant peripheral nerve sheath tumors (MPNST). Staining for p16INK4a, Ki67, p53 and CyclinD1 was performed in all the cases. Additionally, ß-galactosidase staining was done in those cases in which frozen tissue was available (n=8). Results: Higher levels of p16INK4a (p=0.0001) and lower levels of Ki67 (p=0.0001) were found in Schwannomas. Beta-galactosidase activity was positive in 5/5 Schwannomas and negative in 3/3 MPNST. Conclusions: Our results support the senescence nature of Schwannomas and the absence of a senescence phenotype in MPNST.

21. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: A Sarculator-based risk stratification analysis of the ISG-STS 1001 randomized trial

Author

Sandro Pasquali, Emanuela Palmerini, Vittorio Quagliuolo, Javier Martin‐Broto, Antonio Lopez‐Pousa, Giovanni Grignani, Antonella Brunello, Jean‐Yves Blay, Oscar Tendero, Robert Diaz‐Beveridge, Virginia Ferraresi, Iwona Lugowska, Gabriele Infante, Luca Braglia, Domenico Franco Merlo, Valeria Fontana, Emanuela Marchesi, Davide Maria Donati, Elena Palassini, Giuseppe Bianchi, Andrea Marrari, Carlo Morosi, Silvia Stacchiotti, Silvia Bagué, Jean Michel Coindre, Angelo Paolo Dei Tos, Piero Picci, Paolo Bruzzi, Rosalba Miceli, Paolo Giovanni Casali, Alessandro Gronchi, Carla Dani, Chiara Villa, Antonella Messina, Lorella Rusi, Anna Maria Nuzzo, Carmen Nuzzo, Antonino De Paoli, Angela Buonadonna, Alessandro Comandone, Antonella Boglione, Lorenzo Livi, Daniela Greto, Nada Riva, Manuela Monti, Elisabetta Pennacchioli, Tommaso De Pas, Vincenzo Ippolito, Patrico Ledesma, Andres Redondo, Claudia Valverde, Raquel Bratos, Josefina Cruz, Javier Martinez Trufero, Ricardo Cubedo, Isabel Sevilla, Pablo Luna, Rafael Lopez, Pilar Sancho, Olivia Bally, Mehdi Brahmi, Isabelle Ray‐Coquard, Philippe Cassier, Nathalie Marques, Luis Tassy, Pascaline Boudou‐Rouquette, Camille Tlemsani, Jerome Alexandre, Francois Goldwasser, Emmanuelle Bompas, Frederic Rolland, Christophe Perrin, Marie Talarmin, Antoine Italiano, Maud Toulmonde, Mathieu Laramas, Jacques‐Olivier Bay, Pascale Dubray‐Longeras, Piotr Rutkowski, PharmaMar, European Commission, Pasquali, Sandro, Palmerini, Emanuela, Grignani, Giovanni, Brunello, Antonella, Blay, Jean-Yves, Stacchiotti, Silvia, Pasquali S., Palmerini E., Quagliuolo V., Martin-Broto J., Lopez-Pousa A., Grignani G., Brunello A., Blay J.-Y., Tendero O., Diaz-Beveridge R., Ferraresi V., Lugowska I., Infante G., Braglia L., Merlo D.F., Fontana V., Marchesi E., Donati D.M., Palassini E., Bianchi G., Marrari A., Morosi C., Stacchiotti S., Bague S., Coindre J.M., Dei Tos A.P., Picci P., Bruzzi P., Miceli R., Casali P.G., Gronchi A., Dani C., Villa C., Messina A., Rusi L., Nuzzo A.M., Nuzzo C., De Paoli A., Buonadonna A., Comandone A., Boglione A., Livi L., Greto D., Riva N., Monti M., Pennacchioli E., De Pas T., Ippolito V., Ledesma P., Redondo A., Valverde C., Bratos R., Cruz J., Martinez Trufero J., Cubedo R., Sevilla I., Luna P., Lopez R., Sancho P., Bally O., Brahmi M., Ray-Coquard I., Cassier P., Marques N., Tassy L., Boudou-Rouquette P., Tlemsani C., Alexandre J., Goldwasser F., Bompas E., Rolland F., Perrin C., Talarmin M., Italiano A., Toulmonde M., Laramas M., Bay J.-O., Dubray-Longeras P., and Rutkowski P.

Subjects
Oncology, Adult, Cancer Research, medicine.medical_specialty, sarcoma, Anthracycline, medicine.medical_treatment, Soft Tissue Neoplasms, Lower risk, chemotherapy, Risk Assessment, nomogram, Interquartile range, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Ifosfamide, Chemotherapy, business.industry, Soft tissue sarcoma, neoadjuvant, clinical trial, Nomogram, medicine.disease, Neoadjuvant Therapy, Chemotherapy, Adjuvant, chemotherapy, clinical trial, neoadjuvant, nomogram, sarcoma, Sarcoma, business, medicine.drug
Abstract

[Background] The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS., [Methods] This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS < 60%) and lower risk subgroups (10-year pr-OS ≥ 60%)., [Results] The median pr-OS was 0.63 (interquartile range [IQR], 0.51-0.72) for the entire study population, 0.62 (IQR, 0.51-0.70) for the AI arm, and 0.64 (IQR, 0.51-0.73) for the HT arm. Three- and 5-year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82-0.93) and 0.81 (95% CI, 0.71-0.86) in lower risk patients and 0.69 (95% CI, 0.70-0.85) and 0.59 (95% CI, 0.51-0.72) in the higher risk patients (log-rank test, P = .004). In higher risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105)., [Conclusions] High-risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS., This was a nonfunded analysis. In the ISG-STS 1001 trial, PharmaMar provided trabectedin for the HG-MRLPS cohort. That trial was partially funded through a European Union grant (EUROSARC FP7 278472).

Published
2022

22. Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups

Author

Giovanni Grignani, Emanuela Marchesi, Carlo Morosi, Piero Picci, Robert Diaz Beveridge, Silvia Bagué, Paolo Bruzzi, Virginia Ferraresi, Davide Maria Donati, Angelo Paolo Dei Tos, Antonio López Pousa, Giuseppe Bianchi, Paolo G. Casali, Silvia Stacchiotti, Iwona Lugowska, Antonella Brunello, Jean Michel Coindre, Javier Martin Broto, Oscar Tendero, Emanuela Palmerini, Jean-Yves Blay, Elena Palassini, Luca Braglia, Valeria Fontana, Domenico Franco Merlo, Alessandro Gronchi, Andrea Marrari, Vittorio Quagliuolo, European Commission, PharmaMar, Gronchi A., Palmerini E., Quagliuolo V., Broto J.M., Lopez Pousa A., Grignani G., Brunello A., Blay J.-Y., Tendero O., Diaz Beveridge R., Ferraresi V., Lugowska I., Franco Merlo D., Fontana V., Marchesi E., Braglia L., Maria Donati D., Palassini E., Bianchi G., Marrari A., Morosi C., Stacchiotti S., Bague S., Coindre J.M., Dei Tos A.P., Picci P., Bruzzi P., and Casali P.G.

Subjects
0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Anthracycline, medicine.medical_treatment, Soft Tissue Neoplasms, Disease-Free Survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, soft tissue sarcoma, neoadjuvant chemotherapy, Humans, Prospective Studies, Prospective cohort study, Neoadjuvant therapy, Chemotherapy, Ifosfamide, business.industry, Sarcoma, Middle Aged, medicine.disease, Neoadjuvant Therapy, 3. Good health, Clinical trial, 030104 developmental biology, Italy, Spain, 030220 oncology & carcinogenesis, Female, France, Poland, business, medicine.drug
Abstract

[Purpose] To determine whether the administration of histology-tailored neoadjuvant chemotherapy (HT) was superior to the administration of standard anthracycline plus ifosfamide neoadjuvant chemotherapy (A+I) in high-risk soft tissue sarcoma (STS) of an extremity or the trunk wall., [Patients and methods] This was a randomized, open-label, phase III trial. Patients had localized high-risk STS (grade 3; size, ≥ 5 cm) of an extremity or trunk wall, belonging to one of the following five histologic subtypes: high-grade myxoid liposarcoma (HG-MLPS); leiomyosarcoma (LMS), synovial sarcoma (SS), malignant peripheral nerve sheath tumor (MPNST), and undifferentiated pleomorphic sarcoma (UPS). Patients were randomly assigned in a 1:1 ratio to receive three cycles of A+I or HT. The HT regimens were as follows: trabectedin in HG-MLPS; gemcitabine plus dacarbazine in LMS; high-dose prolonged-infusion ifosfamide in SS; etoposide plus ifosfamide in MPNST; and gemcitabine plus docetaxel in UPS. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), estimated using the Kaplan-Meier method and compared using Cox models adjusted for treatment and stratification factors. The study is registered at ClinicalTrials.gov (identifier NCT01710176)., [Results] Between May 2011 and May 2016, 287 patients (UPS: n = 97 [33.8%]; HG-MLPS: n = 65 [22.6%]; SS: n = 70 [24.4%]; MPNST: n = 27 [9.4%]; and LMS: n = 28 [9.8%]) were randomly assigned to either A+I or HT. At the final analysis, with a median follow-up of 52 months, the projected DFS and OS probabilities were 0.55 and 0.47 (log-rank P = .323) and 0.76 and 0.66 (log-rank P = .018) at 60 months in the A+I arm and HT arm, respectively. No treatment-related deaths were observed., [Conclusions] In a population of patients with localized high-risk STS, HT was not associated with a better DFS or OS, suggesting that A+I should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk STS., Partially funded through a European Union grant (EUROSARC FP7 278472; A.G.) and PharmaMar (A.G.). The French sites were supported by awards to J.-Y.B. from NETSARC, LYRICAN (INCA-DGOS-INSERM 12563) and DEPGYN (RHU4).

Published
2020

23. Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy.

Author

Pasquali S, Vallacchi V, Lalli L, Collini P, Barisella M, Romagosa C, Bague S, Coindre JM, Dei Tos AP, Palmerini E, Quagliuolo V, Martin-Broto J, Lopez-Pousa A, Grignani G, Blay JY, Beveridge RD, Casiraghi E, Brich S, Renne SL, Bergamaschi L, Vergani B, Sbaraglia M, Casali PG, Rivoltini L, Stacchiotti S, and Gronchi A

Subjects
Humans, Female, Male, Prognosis, Middle Aged, Adult, Aged, Treatment Outcome, Tumor Microenvironment immunology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor, Immunohistochemistry, Neoadjuvant Therapy, Sarcoma drug therapy, Sarcoma mortality, Sarcoma immunology, Sarcoma pathology, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism
Abstract

Background: Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune infiltrate. This study characterized immune infiltrate spatial distribution after NAC in primary high-risk soft tissue sarcomas (STS) and investigate association with prognosis., Methods: The ISG-STS 1001 trial randomized STS patients to anthracycline plus ifosfamide (AI) or a histology-tailored (HT) NAC. Four areas of tumour specimens were sampled: the area showing the highest lymphocyte infiltrate (HI) at H&E; the area with lack of post-treatment changes (highest grade, HG); the area with post-treatment changes (lowest grade, LG); and the tumour edge (TE). CD3, CD8, PD-1, CD20, FOXP3, and CD163 were analyzed at immunohistochemistry and digital pathology. A machine learning method was used to generate sarcoma immune index scores (SIS) that predict patient disease-free and overall survival (DFS and OS)., Findings: Tumour infiltrating lymphocytes and PD-1+ cells together with CD163+ cells were more represented in STS histologies with complex compared to simple karyotype, while CD20+ B-cells were detected in both these histology groups. PD-1+ cells exerted a negative prognostic value irrespectively of their spatial distribution. Enrichment in CD20+ B-cells at HI and TE areas was associated with better patient outcomes. We generated a prognostic SIS for each tumour area, having the HI-SIS the best performance. Such prognostic value was driven by treatment with AI., Interpretation: The different spatial distribution of immune populations and their different association with prognosis support NAC as a modifier of tumour immune infiltrate in STS., Funding: Pharmamar; Italian Ministry of Health [RF-2019-12370923; GR-2016-02362609]; 5 × 1000 Funds-2016, Italian Ministry of Health; AIRC Grant [ID#28546]., Competing Interests: Declaration of interests Sandro Pasquali reports institutional research funds from Pharmamar, Ikena Oncology, and ASTX Pharmaceutical. Cleofe Romagosa reports institutional research funds from Pharmamar. Angelo Paolo Dei Tos reports institutional research funds from Pharmamar. Javier Martin-Broto reports institutional research funds from Pharmamar, Adaptimmune, Amgen, AROG, Bayer, Blueprint, BMS, Celgene, Daiichi Sankyo, Deciphera, Eisai, Forma, GSK, IMMIX Biopharma, Karyopharm, Lilly, LIXTE, Nektar, Novartis, Pfizer, Roche, and PharmaMar and compensations for advisory board or consulting relationship from Tecnofarma. Jean-Yves Blay reports compensations for advisory board or consulting relationship with Merck Sharp & Dohme, Merck Serono, Daiichi-Sankyo, Astellas, Alexo Oncology, Samyang Biopharm, Hanmi, Daewoong and Amgen and has received institutional research funds from Genentech/Roche, Merck Sharp & Dohme, Merck Serono, Daiichi-Sankyo, Astellas and Amgen. Giovanni Grignani reports institutional research funds from Eli Lilly and Company, GlaxoSmithKline, Merk, Novartis, and Pharmamar. Emanuela Palmerini reports compensations for advisory boards from Daiichi Sankyo Company, Daiichi Sankyo Europe GmbH, Deciphera Pharmaceuticals Inc., EUSA Pharma (US) LLC, and SynOx Therapeutics. Paolo Casali received honoraria for speaker, consultancy, or advisory roles from: Bayer, Deciphera, Eisai, Eli Lilly, and Pfizer; his unit received funds from: Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Glaxo, Karyopharm Pharmaceuticals, Novartis, Pfizer, and PharmaMar. Silvia Stacchiotti reports institutional research funds from: Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Glaxo Smith Kline, Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar, and SpringWorks; honoraria, consultancy, or advisory role from: Bayer, Bavarian Nordic, Boehringer, Deciphera, Daiichi Sankyo Pharma, Gentili, Glaxo Smith Kline, Inhibrix, Maxivax, PharmaMar, and Servier; travel, accommodations, expenses from: PharmaMar. Alessandro Gronchi reports compensations for advisory boards from Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks, and Deciphera and institutional research grants from PharmaMar and Nanobiotix. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
Full Text
View/download PDF

24. Somatic PIK3CA mutations as a driver of sporadic venous malformations.

Author

Castel P, Carmona FJ, Grego-Bessa J, Berger MF, Viale A, Anderson KV, Bague S, Scaltriti M, Antonescu CR, Baselga E, and Baselga J

Subjects
Animals, Class I Phosphatidylinositol 3-Kinases, Embryo, Mammalian blood supply, Embryo, Mammalian drug effects, Embryo, Mammalian pathology, Endothelial Cells metabolism, Integrases metabolism, Mice, Neovascularization, Physiologic drug effects, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Skin blood supply, Skin pathology, Spinal Cord blood supply, Spinal Cord pathology, Vascular Malformations drug therapy, Mutation genetics, Phosphatidylinositol 3-Kinases genetics, Vascular Malformations enzymology, Vascular Malformations genetics
Abstract

Venous malformations (VM) are vascular malformations characterized by enlarged and distorted blood vessel channels. VM grow over time and cause substantial morbidity because of disfigurement, bleeding, and pain, representing a clinical challenge in the absence of effective treatments (Nguyenet al, 2014; Uebelhoeret al, 2012). Somatic mutations may act as drivers of these lesions, as suggested by the identification of TEK mutations in a proportion of VM (Limayeet al, 2009). We report that activating PIK3CA mutations gives rise to sporadic VM in mice, which closely resemble the histology of the human disease. Furthermore, we identified mutations in PIK3CA and related genes of the PI3K (phosphatidylinositol 3-kinase)/AKT pathway in about 30% of human VM that lack TEK alterations. PIK3CA mutations promote downstream signaling and proliferation in endothelial cells and impair normal vasculogenesis in embryonic development. We successfully treated VM in mouse models using pharmacological inhibitors of PI3Kα administered either systemically or topically. This study elucidates the etiology of a proportion of VM and proposes a therapeutic approach for this disease., (Copyright © 2016, American Association for the Advancement of Science.)

Published
2016
Full Text
View/download PDF

25. Clinical practice guidelines for the diagnosis and treatment of patients with soft tissue sarcoma by the Spanish group for research in sarcomas (GEIS).

Author

Garcia del Muro X, de Alava E, Artigas V, Bague S, Braña A, Cubedo R, Cruz J, Mulet-Margalef N, Narvaez JA, Martinez Tirado O, Valverde C, Verges R, Viñals J, and Martin-Broto J

Subjects
Antineoplastic Agents therapeutic use, Chemotherapy, Adjuvant methods, Humans, Sarcoma diagnosis, Sarcoma pathology, Soft Tissue Neoplasms diagnosis, Soft Tissue Neoplasms pathology, Spain, Sarcoma therapy, Soft Tissue Neoplasms therapy
Abstract

Soft tissue sarcomas (STS) constitute an uncommon and heterogeneous group of tumours, which require a complex and specialized multidisciplinary management. The diagnostic approach should include imaging studies and core needle biopsy performed prior to undertaking surgery. Wide excision is the mainstay of treatment for localized sarcoma, and associated preoperative or postoperative radiotherapy should be administered in high-risk patients. Adjuvant chemotherapy was associated with a modest improvement in survival in a meta-analysis and constitutes a standard option in selected patients with high-risk STS. In metastatic patients, surgery must be evaluated in selected cases. In the rest of patients, chemotherapy and, in some subtypes, targeted therapy often used in a sequential strategy constitutes the treatment of election. Despite important advances in the understanding of the pathophysiology of the disease, the advances achieved in therapeutic results may be deemed still insufficient. Moreover, due to the rarity and complexity of the disease, the results in clinical practice are not always optimal. For this reason, the Spanish Group for Research on Sarcoma (GEIS) has developed a multidisciplinary clinical practice guidelines document, with the aim of facilitating the diagnosis and treatment of these patients in Spain. In the document, each practical recommendation is accompanied by level of evidence and grade of recommendation on the basis of the available data.

Published
2016
Full Text
View/download PDF

26. MRP1 overexpression determines poor prognosis in prospectively treated patients with localized high-risk soft tissue sarcoma of limbs and trunk wall: an ISG/GEIS study.

Author

Martin-Broto J, Gutierrez AM, Ramos RF, Lopez-Guerrero JA, Ferrari S, Stacchiotti S, Picci P, Calabuig S, Collini P, Gambarotti M, Bague S, Dei Tos AP, Palassini E, Luna P, Cruz J, Cubedo R, Martinez-Trufero J, Poveda A, Casali PG, Fernandez-Serra A, Lopez-Pousa A, and Gronchi A

Subjects
ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Aged, Anthracyclines administration & dosage, Disease-Free Survival, Drug Resistance, Multiple genetics, Extremities pathology, Female, Gene Expression Regulation, Neoplastic, Glutathione Transferase genetics, Humans, Male, Middle Aged, Multidrug Resistance-Associated Proteins genetics, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Prognosis, Sarcoma drug therapy, Sarcoma mortality, Sarcoma pathology, ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis, Glutathione Transferase biosynthesis, Multidrug Resistance-Associated Proteins biosynthesis, Neoplasm Recurrence, Local genetics, Sarcoma genetics
Abstract

Patients with localized high-risk soft tissue sarcomas (STS) of the limbs and trunk wall still have a considerable metastatic recurrence rate of more than 50%, in spite of adjuvant chemotherapy. This drug-ceiling effect of chemotherapy in sarcoma setting could be explained, at least partially, by multidrug resistance (MDR) mechanisms. The aim of this study was to ascertain whether mRNA and protein expression of ABCB1 (P-glycoprotein), ABCC1 (MRP1), and GSTA1 (glutathione S-transferase pi) was prognostic in localized high-risk STS. Immunohistochemistry and reverse transcriptase-PCR studies were performed from biopsies at the time of diagnosis. Patients of this series were prospectively enrolled into a phase III trial that compared three versus five cycles of epirubicin plus ifosfamide. The series of 102 patients found 41 events of recurrence and 37 of death with a median follow-up of 68 months. In univariate analysis, variables with a statistically significant relationship with relapse-free survival (RFS) were: MRP1 expression (5-year RFS rate of 23% in positive cases and 63% in negative cases, P = 0.029), histology (5-year RFS rate of 74% in undifferentiated pleomorphic sarcoma and 43% in synovial sarcoma, P = 0.028), and ABCC1 expression (5-year RFS rate of 33% in overexpression and 65% in downregulation, P = 0.012). Combined ABCC1/MRP1 was the only independent prognostic factor for both RFS (HR = 2.704, P = 0.005) and overall survival (HR = 2.208, P = 0.029). ABCC1/MRP1 expression shows robust prognostic relevance in patients with localized high-risk STS treated with anthracycline-based chemotherapy, which is the standard front line treatment in STS. This finding deserves attention as it points to a new targetable protein in STS.

Published
2014
Full Text
View/download PDF

27. Role of tumor-associated macrophages and angiogenesis in desmoid-type fibromatosis.

Author

Romero S, Szafranska J, Cabrera E, Gonzalez A, Peiró A, Llauger J, Ortega L, Bague S, Canet B, Espinosa I, and Prat J

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Female, Fibromatosis, Aggressive genetics, Fibromatosis, Aggressive mortality, Genotype, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Male, Middle Aged, Polymerase Chain Reaction, Prognosis, Tissue Array Analysis, Young Adult, beta Catenin genetics, Fibromatosis, Aggressive pathology, Macrophages pathology, Neovascularization, Pathologic pathology
Abstract

Desmoid-type fibromatosis (DTF) is a rare soft tissue tumor with fibroblastic features affecting two to four individuals per million population per year. Despite its bland microscopic appearance, the tumor behaves aggressively. Although unable to metastasize, DTF tends to recur and local recurrences in anatomically critical sites can be fatal. Tumor-associated macrophages (TAM) play an important role in tumor development through the activation of angiogenesis, particularly in cases of epithelial malignancies. The aim of this study is to investigate the prognostic significance of TAMs and the number of microvessels in DTF. Tumor macrophages (CD163), microvessel density (CD31), and beta-catenin were investigated on 69 primary DTF cases with follow-up information. CTNNB1 mutations were also studied. High density of tumor macrophages and high number of microvessels were associated with a significantly worse recurrence-free survival (P = 0.03 and P = 0.007, respectively). There was a significant correlation between microvessel density and CD163 macrophages (P = 0.02). Furthermore, combination of high number of tumor macrophages and high microvessel density greatly improved the statistical significance (P = 0.000005). Macrophages and microvessels may play an important role in the biologic behavior of DTF. This finding could help in the clinical management of patients with DTF.

Published
2012
Full Text
View/download PDF

28. Dermatofibrosarcoma protuberans presenting as a subcutaneous mass: a clinicopathological study of 15 cases with exclusive or near-exclusive subcutaneous involvement.

Author

Bague S and Folpe AL

Subjects
Adolescent, Adult, Aged, Child, Dermatofibrosarcoma metabolism, Diagnosis, Differential, Female, Humans, Immunohistochemistry, Male, Middle Aged, Skin Neoplasms metabolism, Dermatofibrosarcoma pathology, Skin Neoplasms pathology, Soft Tissue Neoplasms pathology, Subcutaneous Tissue pathology
Abstract

Dermatofibrosarcoma protuberans (DFSP), a cutaneous fibrohistiocytic tumor of intermediate (borderline) malignancy, typically arises in the dermis and subsequently infiltrates the subcutaneous tissue. Very rarely DFSP may either arise within the subcutaneous fat without dermal involvement or show very extensive subcutaneous involvement with only minimal and clinically subtle dermal involvement. We present the clinicopathological features of 15 cases of DFSP showing exclusive or near-exclusive involvement of the subcutaneous fat. The differential diagnosis with other subcutaneous spindle cell neoplasms is emphasized. Awareness of this rare subset of DFSP should prevent its misdiagnosis as other less aggressive tumor types.

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results