MDM2 and CDK4 Immunohistochemical Coexpression in High-grade Osteosarcoma: Correlation With a Dedifferentiated Subtype
Abstract
Low-grade osteosarcomas comprise a distinct subset of osteosarcomas. They may occasionally dedifferentiate into high-grade tumors, typically in the form of high-grade osteosarcoma, which are histologically indistinguishable from conventional osteosarcomas. MDM2 and CDK4 are often amplified in low-grade osteosarcomas and their dedifferentiated counterparts, and the encoded proteins are accordingly overexpressed. As MDM2/CDK4 expression was reportedly rare in conventional osteosarcoma, we hypothesized that these markers may help separate dedifferentiated osteosarcoma from the conventional type. To test this, we performed MDM2 and CDK4 immunohistochemistry on 81 primary and 26 recurrent/metastatic high-grade osteosarcomas and correlated these data with the histology of the primary resection material, with particular attention to the potential presence of any coexisting low-grade osteosarcomatous components. MDM2 and CDK4 coexpression was identified in 7 cases, and on careful histologic review 6 of them were discovered to contain foci of coexisting low-grade elements. One case was a known dedifferentiated parosteal osteosarcoma, and the remaining 5 cases were newly identified dedifferentiated osteosarcomas in which the limited low-grade components were originally unrecognized. An additional 11 cases expressed either marker alone, whereas the remaining 89 cases were negative for both markers; no resection material from these 100 cases presented with a low-grade component. MDM2/CDK4 gene amplification status, determined by quantitative polymerase chain reaction in selected cases, was largely concordant with immunoexpression. Our data suggest that MDM2 and CDK4 coexpression in high-grade osteosarcomas is sensitive and specific to those that progressed from low-grade osteosarcomas, and immunohistochemistry may help identify this dedifferentiated subgroup to facilitate accurate subclassification.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Co-amplification of MDM2 and CDK4 has been reported in several types of cancers including sarcoma, glioblastoma, bladder cancer and gastric cancer.
“Moreover, the co-amplification of MDM2 and CDK4 has been reported in several type of cancers including sarcoma, glioblastoma, bladder cancer, gastric cancer, etc.40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50”
Cites
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy
Tovar, C., Rosinski, J., Filipovic, Z., Higgins, B., Kolinsky, K., Hilton, H., Zhao, X., Vu, B. T., Qing, W., Packman, K., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507493103 · Cited by 708 · see citing works
Binh, M. B. N., Sastre‐Garau, X., Guillou, L., Pinieux, G. D. B. D., Terrier, P., Lagacé, R., Aurias, A., Hostein, I., & Coindre, J. (2005) · The American Journal of Surgical Pathology · doi:10.1097/01.pas.0000170343.09562.39 · Cited by 642 · see citing works
MDM2 gene amplification in metastatic osteosarcoma.
Ladanyi, M., Cha, C. H., Lewis, R., Jhanwar, S. C., Huvos, A. G., & Healey, J. H. (1993) · PubMed · Cited by 342 · see citing works
Parosteal osteosarcoma. A clinicopathological study.
Okada, K., Frassica, F. J., Sim, F. H., Beabout, J. W., Bond, J. R., & Unni, K. K. (1994) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-199403000-00007 · Cited by 245 · see citing works
Dujardin, F., Binh, M. B. N., Bouvier, C., Gomez‐Brouchet, A., Larousserie, F., Muret, A. D., Louis‐Brennetot, C., Aurias, A., Coindre, J., Guillou, L., et al. (2011) · Modern Pathology · doi:10.1038/modpathol.2010.229 · Cited by 243 · see citing works
Coindre, J., Mariani, O., Chibon, F., Mairal, A., Somerhausen, N. D. S. A., Favre-Guillevin, E., Nguyen, B. B., Stoeckle, E., Hostein, I., & Aurias, A. (2003) · Modern Pathology · doi:10.1097/01.mp.0000056983.78547.77 · Cited by 218 · see citing works
Yoshida, A., Ushiku, T., Motoi, T., Shibata, T., Beppu, Y., Fukayama, M., & Tsuda, H. (2010) · Modern Pathology · doi:10.1038/modpathol.2010.124 · Cited by 191 · see citing works
Self-citationBrämswig, J., Heimes, U., Heiermann, E., Schlegel, W., Nieschlag, E., & Schellong, G. (1990) · Cancer · doi:10.1002/1097-0142(19900315)65:6 · Cited by 172 · see citing works
Coindre, J., Hostein, I., Maire, G., Derré, J., Guillou, L., Leroux, A., Ghnassia, J., Collin, F., Pédeutour, F., & Aurias, A. (2004) · The Journal of Pathology · doi:10.1002/path.1579 · Cited by 154 · see citing works
Wunder, J. S., Eppert, K., Burrow, S., Gogkoz, N., Bell, R. S., & Andrulis, I. L. (1999) · Oncogene · doi:10.1038/sj.onc.1202346 · Cited by 152 · see citing works
Dedifferentiated parosteal osteosarcoma.
Wold, L. E., Unni, K. K., Beabout, J. W., Sim, F. H., & Dahlin, D. C. (1984) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-198466010-00008 · Cited by 145 · see citing works
Dedifferentiated parosteal osteosarcoma: The experience of the Rizzoli Institute
Bertoni, F., Bacchini, P., Staals, E. L., & Davidovitz, P. (2005) · Cancer · doi:10.1002/cncr.21039 · Cited by 138 · see citing works
Campanacci, M., Picci, P., Gherlinzoni, F., Guerra, A., Bertoni, F., & Neff (1984) · Journal of Bone and Joint Surgery - British Volume · doi:10.1302/0301-620x.66b3.6586725 · Cited by 127 · see citing works
Guo, W., Lonardo, F., Ueda, T., Kim, T. K., Huvos, A. G., Healey, J. H., & Ladanyi, M. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990118)80:2 · Cited by 120 · see citing works
Mejia‐Guerrero, S., Quejada, M., Gokgoz, N., Gill, M., Parkes, R. K., Wunder, J. S., & Andrulis, I. L. (2010) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.20761 · Cited by 120 · see citing works
Bréchot, J.-M., Chevret, S., Charpentier, M.-C., Vecchi, C. A. D., Capron, F., Prudent, J., Rochemaure, J., & Chastang, C. (1996) · Cancer · doi:10.1002/(sici)1097-0142(19961115)78:10 · Cited by 103 · see citing works
Szymanska, J., Mandahl, N., Mertens, F., Tarkkanen, M., Karaharju, E. O., & Knuutila, S. (1996) · Genes Chromosomes and Cancer · doi:10.1002/(sici)1098-2264(199605)16:1 · Cited by 102 · see citing works
Differentially amplified chromosome 12 sequences in low‐ and high‐grade osteosarcoma
Gisselsson, D., Pålsson, E., Höglund, M., Domanski, H. A., Mertens, F., Pandis, N., Sciot, R., Cin, P. D., Bridge, J. A., & Mandahl, N. (2001) · Genes Chromosomes and Cancer · doi:10.1002/gcc.1219 · Cited by 83 · see citing works
Analysis of 12q13-15 Genes in Parosteal Osteosarcoma
Gamberi, G., Ragazzini, P., Benassi, M. S., Ferrari, C., Sollazzo, M. R., Molendini, L., Merli, M., Magagnoli, G., Ruggieri, P., Balladelli, A., et al. (2000) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-200008000-00026 · Cited by 52 · see citing works
A Comparison of Intramedullary and Juxtacortical Low-grade Osteogenic Sarcoma
Schwab, J. H., Antonescu, C. R., Athanasian, E. A., Boland, P. J., Healey, J. H., & Morris, C. D. (2008) · Clinical Orthopaedics and Related Research · doi:10.1007/s11999-008-0251-2 · Cited by 52 · see citing works
L??pez-Guerrero, J. A., L??pez-Gin??s, C., Pell??n, A., Cardá, C., & Llombart‐Bosch, A. (2004) · Diagnostic Molecular Pathology · doi:10.1097/00019606-200406000-00004 · Cited by 52 · see citing works
Analysis of SAS Gene and CDK4 and MDM2 Proteins in Low-Grade Osteosarcoma
Ragazzini, Gamberi, BENASSI, V., Orlando, Sestini, R., Ferrari, C., Molendini, Sollazzo, V., Merli, Magagnoli, G., et al. (1999) · Cancer Detection and Prevention · doi:10.1046/j.1525-1500.1999.09907.x · Cited by 52 · see citing works
Yokoyama, R., Schneider‐Stock, R., Radig, K., Wex, T., & Roessner, A. (1998) · Pathology - Research and Practice · doi:10.1016/s0344-0338(98)80096-4 · Cited by 51 · see citing works
Kawaguchi, K.-I., Oda, Y., Sakamoto, A., Saito, T., Tamiya, S., Iwamoto, Y., & Tsuneyoshi, M. (2002) · Modern Pathology · doi:10.1097/01.mp.0000024264.48690.ea · Cited by 47 · see citing works
Bauknecht, T., Angel, P. E., Kohler, M., Kommoss, F., Birmelin, G., Pfleiderer, A., & Wagner, E. (1993) · Cancer · doi:10.1002/1097-0142(19930115)71:2 · Cited by 39 · see citing works
Shuhaibar, H., & Friedman, L. (1998) · Skeletal Radiology · doi:10.1007/s002560050440 · Cited by 20 · see citing works
Kenan, S., Ginat, D. T., & Steiner, G. C. (2006) · Skeletal Radiology · doi:10.1007/s00256-006-0123-3 · Cited by 19 · see citing works
Inokuchi, K., Shinohara, T., Futaki, M., Hanawa, H., Tanosaki, S., Yamaguchi, H., Nomura, T., & Dan, K. (1998) · Genes Chromosomes and Cancer · doi:10.1002/(sici)1098-2264(199811)23:3 · Cited by 16 · see citing works
Mackenney, R., & Oni, O. O. A. (1984) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-198466020-00027 · Cited by 12 · see citing works
Flagged first, then by citations
2 of the 31 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Suehara, Y., Alex, D., Bowman, A., Middha, S., Zehir, A., Chakravarty, D., Wang, L., Jour, G., Nafa, K., Hayashi, T., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-4032 · Cited by 135 · see citing works
Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies
Rathore, R., & Tine, B. A. V. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10061182 · Cited by 122 · see citing works
MDM2 Amplified Sarcomas: A Literature Review
Sciot, R. (2021) · Diagnostics · doi:10.3390/diagnostics11030496 · Cited by 96 · see citing works
Hang, J., & Chen, P. C.-H. (2014) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2013-0030-rs · Cited by 85 · see citing works
Wang, B., Peng, F., Huang, W., Zhou, J., Zhang, N., Sheng, J., Haruehanroengra, P., He, G., & Han, B. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.12.013 · Cited by 73 · see citing works
Tumors of soft tissue and bone
Chu, P. G., & Weiss, L. M. (2000) · Cambridge University Press eBooks · doi:10.1017/cbo9781316167366.010 · Cited by 66 · see citing works
Tabareau-Delalande, F., Collin, C., Gomez‐Brouchet, A., Bouvier, C., Decouvelaere, A., Muret, A. D., Pagès, J., & Pinieux, G. D. B. D. (2014) · Modern Pathology · doi:10.1038/modpathol.2014.80 · Cited by 63 · see citing works
Yoshida, A. (2021) · Surgical pathology clinics · doi:10.1016/j.path.2021.06.003 · Cited by 59 · see citing works
Self-citationMartin, J. W., Chilton‐MacNeill, S., Koti, M., van Wijnen, A. J., Squire, J. A., & Zieleńska, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095843 · Cited by 56 · see citing works
Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma
He, X., Pang, Z., Zhang, X., Lan, T., Chen, H., Chen, M., Yang, H., Huang, J., Chen, Y., Zhang, Z., et al. (2018) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001125 · Cited by 50 · see citing works
Molecular pathogenesis and therapeutic strategies of human osteosarcoma
Denduluri, S. K., Wang, Z., Yan, Z., Wang, J., Wei, Q., Mohammed, M. K., Haydon, R. C., Luu, H. H., & He, T. (2016) · Journal of Biomedical Research · doi:10.7555/jbr.29.20150075 · Cited by 45 · see citing works
Laitinen, M., Parry, M., Albergo, J. I., Jeys, L. M., Abudu, A., Carter, S. R., Sumathi, V. P., & Grimer, R. J. (2015) · The Bone & Joint Journal · doi:10.1302/0301-620x.97b12.35749 · Cited by 44 · see citing works
Dembla, V., Somaiah, N., Barata, P. C., Hess, K. R., Fu, S., Jankú, F., Karp, D. D., Naing, A., Piha-Paul, S. A., Subbiah, V., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.26075 · Cited by 41 · see citing works
MDM2 and CDK4 expression in periosteal osteosarcoma
Righi, A., Gambarotti, M., Benini, S., Gamberi, G., Cocchi, S., Picci, P., & Bertoni, F. (2015) · Human Pathology · doi:10.1016/j.humpath.2014.12.006 · Cited by 42 · see citing works
Martins‐Neves, S. R., Sampaio-Ribeiro, G., & Gomes, C. M. F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098401 · Cited by 43 · see citing works
Chow, L. T. C. (2016) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-016-1926-9 · Cited by 41 · see citing works
A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification
Guérin, M., Thariat, J., Ouali, M., Bouvier, C., Decouvelaere, A., Cassagnau, E., Aubert, S., Lepreux, S., Coindre, J., Valmary‐Degano, S., et al. (2015) · Human Pathology · doi:10.1016/j.humpath.2015.11.012 · Cited by 37 · see citing works
Bone- and Cartilage-Forming Tumors and Ewing Sarcoma: An Update with a Gnathic Emphasis
Stewart, B. D., Reith, J. D., Knapik, J. A., & Chi, A. C. (2014) · Head and Neck Pathology · doi:10.1007/s12105-014-0587-8 · Cited by 32 · see citing works
GRM1 Immunohistochemistry Distinguishes Chondromyxoid Fibroma From its Histologic Mimics
Toland, A. M. S., Lam, S. W., Varma, S., Wang, A., Howitt, B. E., Kunder, C. A., Kerr, D. A., Szuhai, K., Bovée, J. V. M. G., & Charville, G. W. (2022) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001921 · Cited by 32 · see citing works
Kumar, P., Surya, V., Urs, A. B., Augustine, J., Mohanty, S., & Gupta, S. (2018) · Pathology & Oncology Research · doi:10.1007/s12253-018-0510-9 · Cited by 31 · see citing works
The Utility of MDM2 and CDK4 Immunohistochemistry and MDM2 FISH in Craniofacial Osteosarcoma
Limbach, A. L., Lingen, M. W., McElherne, J., Mashek, H., Fitzpatrick, C. A., Hyjek, E. M., Mostofi, R. S., & Cipriani, N. A. (2020) · Head and Neck Pathology · doi:10.1007/s12105-020-01139-x · Cited by 31 · see citing works
An Update on the Application of Newly Described Immunohistochemical Markers in Soft Tissue Pathology
Lin, G. Y., & Doyle, L. A. (2014) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2014-0488-ra · Cited by 30 · see citing works
Jour, G., Wang, L., Middha, S., Zehir, A., Chen, W., Sadowska, J., Healey, J. H., Agaram, N. P., Choi, L. E., Nafa, K., et al. (2015) · The Journal of Pathology Clinical Research · doi:10.1002/cjp2.29 · Cited by 30 · see citing works
Extraskeletal osteosarcoma: MDM 2 and H3K27me3 analysis of 19 cases suggest disease heterogeneity
Makise, N., Sekimizu, M., Kubo, T., Wakai, S., WATANABE, S.-I. I., Kato, T., Kinoshita, T., Hiraoka, N., Fukayama, M., Kawai, A., et al. (2018) · Histopathology · doi:10.1111/his.13506 · Cited by 28 · see citing works
Self-citationMolecular pathology of bone tumours: diagnostic implications
Puls, F., Niblett, A., & Mangham, D. C. (2013) · Histopathology · doi:10.1111/his.12275 · Cited by 27 · see citing works
Oshiro, H., Tome, Y., Miyake, K., Higuchi, T., Sugisawa, N., Kanaya, F., Nishida, K., & Hoffman, R. M. (2021) · Anticancer Research · doi:10.21873/anticanres.15115 · Cited by 27 · see citing works
Song, M. J., Cho, K., Lee, J.-S., & Song, J. S. (2016) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000365 · Cited by 25 · see citing works
Immunohistochemistry as a Surrogate for Molecular Testing
Swanson, P. E. (2015) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000181 · Cited by 22 · see citing works
A clinical comparison between dedifferentiated low-grade osteosarcoma and conventional osteosarcoma
Toki, S., Kobayashi, E., Yoshida, A., Ogura, K., Wakai, S., Yoshimoto, S., Yonemori, K., & Kawai, A. (2019) · The Bone & Joint Journal · doi:10.1302/0301-620x.101b6.bjj-2018-1207.r1 · Cited by 22 · see citing works
Self-citationTherapeutic Implication of Genomic Landscape of Adult Metastatic Sarcoma
Feng, X., Pleasance, E., Stutheit-Zhao, E. Y., Ng, T., Grewal, J., Mohammad, N., Taylor, S. K., Simmons, C. E., Srikanthan, A., Rassekh, S. R., et al. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00325 · Cited by 21 · see citing works
Righi, A., Paioli, A., Tos, A. P. D., Gambarotti, M., Palmerini, E., Cesari, M., Marchesi, E., Donati, D. M., Picci, P., & Ferrari, S. (2015) · Clinical Sarcoma Research · doi:10.1186/s13569-015-0038-7 · Cited by 20 · see citing works
Hirose, K., Okura, M., Sato, S., Murakami, S., Ikeda, J., Noda, Y., Fukuda, Y., Morii, E., & Toyosawa, S. (2017) · Histopathology · doi:10.1111/his.13141 · Cited by 19 · see citing works
Gregorio, J. D., Giuseppe, L. D., Terreri, S., Rossi, M., Battafarano, G., Pagliarosi, O., Flati, V., & Fattore, A. D. (2024) · Cells · doi:10.3390/cells13060537 · Cited by 18 · see citing works
Locally aggressive fibrous dysplasia
Kashima, T. G., Gamage, N. M., Ye, H., Amary, F. M., Flanagan, A. M., Ostlere, S., & Athanasou, N. A. (2013) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-013-1437-x · Cited by 18 · see citing works
Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials
Zając, W., Dróżdż, J., Kisielewska, W., Karwowska, W., Dudzisz‐Śledź, M., Zając, A. E., Borkowska, A. M., Szumera‐Ciećkiewicz, A., Szostakowski, B., Rutkowski, P. L., et al. (2023) · Cancers · doi:10.3390/cancers15153924 · Cited by 18 · see citing works
Can imaging distinguish between low-grade and dedifferentiated parosteal osteosarcoma?
Lin, H.-Y., Wu, H.-T. H., Wu, P., Wu, C.-L., Chen, P. C.-H., Chen, W., & Guo, W. (2018) · Journal of the Chinese Medical Association · doi:10.1016/j.jcma.2018.01.014 · Cited by 16 · see citing works
Osteosarcoma subtypes based on platelet-related genes and tumor microenvironment characteristics
Shu, Y., Peng, J., Feng, Z., Hu, K., Li, T., Zhu, P., Cheng, T., & Liang, H. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.941724 · Cited by 15 · see citing works
Surface bone sarcomas: an update on current clinicopathological diagnosis and treatment
Savvidou, O. D., Papakonstantinou, O., Lakiotaki, E., Zafeiris, I., Melissaridou, D., Korkolopoulou, P., & Papagelopoulos, P. J. (2021) · EFORT Open Reviews · doi:10.1302/2058-5241.6.210064 · Cited by 15 · see citing works
Decreased local and systemic levels of sFRP3 protein in osteosarcoma patients
Bravo, D., Salduz, A., Shogren, K. L., Okuno, M. N., Herrick, J. L., Okuno, S. H., Galindo, M. A., van Wijnen, A. J., Yaszemski, M. J., & Maran, A. (2018) · Gene · doi:10.1016/j.gene.2018.06.059 · Cited by 14 · see citing works
Molecular and immunohistochemical testing of bone tumours: review and update
Kovacs, S. K., Manassaporn, A., Nielsen, G. P., & Hung, Y. P. (2022) · Histopathology · doi:10.1111/his.14845 · Cited by 13 · see citing works
FISH analysis of selected soft tissue tumors: Diagnostic experience in a tertiary center
Vargas, A. C., Selinger, C. I., Satgunaseelan, L., Cooper, W. A., Gupta, R., Stalley, P., Brown, W., Soper, J., Schatz, J., Boyle, R., et al. (2018) · Asia-Pacific Journal of Clinical Oncology · doi:10.1111/ajco.12980 · Cited by 13 · see citing works
Osteosarcoma: A Comprehensive Morphological and Molecular Review with Prognostic Implications
Motassime, A. E., Vitiello, R., Comodo, R. M., Capece, G., Bocchino, G., Bocchi, M. B., Maccauro, G., & Meschini, C. (2025) · Biology · doi:10.3390/biology14101407 · Cited by 15 · see citing works
Sugiura, Y., Machinami, R., Matsumoto, S., Kanda, H., Ae, K., Takazawa, Y., & Takeuchi, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-94834-w · Cited by 12 · see citing works
Osteosarcoma of the Jaw: Classification, Diagnosis and Treatment
Ferrari, D., Moneghini, L., Allevi, F., Bulfamante, G., & Biglioli, F. (2017) · InTech eBooks · doi:10.5772/67564 · Cited by 12 · see citing works
Low-grade central osteosarcoma arising from bone infarct
Endo, M., Yoshida, T., Yamamoto, H., Ishii, T., Setsu, N., Kohashi, K., Matsunobu, T., Iwamoto, Y., & Oda, Y. (2013) · Human Pathology · doi:10.1016/j.humpath.2012.11.011 · Cited by 12 · see citing works
Significance of MTA1 in the molecular characterization of osteosarcoma
Kim, S. S., & Park, Y.-K. (2014) · Cancer and Metastasis Reviews · doi:10.1007/s10555-014-9523-3 · Cited by 12 · see citing works
The proto‐oncogene function of Mdm2 in bone
Olivos, D. J., Perrien, D. S., Hooker, R. A., Cheng, Y., Fuchs, R. K., Hong, J. M., Bruzzaniti, A., Chun, K. T., Eischen, C. M., Kacena, M. A., et al. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27133 · Cited by 10 · see citing works
Dedifferentiated parosteal osteosarcoma of the maxilla: a case report and review of the literature
MIYASHITA, H., Yoshida, K., Soma, T., Kameyama, K., Sasaki, A., Hisaoka, M., Yazawa, M., Morioka, H., Takahashi, M., Nakagawa, T., et al. (2018) · Journal of Medical Case Reports · doi:10.1186/s13256-018-1747-3 · Cited by 10 · see citing works
Santana, L. A. D. M., Felix, F. A., de Arruda, J. A. A., da Silva, L. P., Brito, É. D. A. C., Takeshita, W. M., & Trento, C. L. (2020) · Oral Surgery Oral Medicine Oral Pathology and Oral Radiology · doi:10.1016/j.oooo.2020.10.009 · Cited by 10 · see citing works
Osteosarcomatous Divergence in Dedifferentiated Liposarcoma Presenting as a Colonic Mass
Gordhandas, J., Lin, G., Tipps, A. M. P., & Zare, S. (2019) · Case Reports in Pathology · doi:10.1155/2019/8025103 · Cited by 9 · see citing works
Liu, L., Sun, J., Liu, S., Zhang, C., & Jiang, L. (2024) · Journal of Stomatology Oral and Maxillofacial Surgery · doi:10.1016/j.jormas.2024.102098 · Cited by 8 · see citing works
Liu, M., Zheng, S.-J., Chen, Y., Li, N., Ren, P.-F., Dai, L.-P., Duan, Z.-P., & Zhang, J.-Y. (2014) · Journal of Immunology Research · doi:10.1155/2014/906532 · Cited by 8 · see citing works
Unlocking bone for proteomic analysis and FISH
Mueller, C., Gambarotti, M., Benini, S., Picci, P., Righi, A., Stevanin, M., Hombach‐Klonisch, S., Henderson, D., Liotta, L. A., & Espina, V. A. (2019) · Laboratory Investigation · doi:10.1038/s41374-018-0168-7 · Cited by 8 · see citing works
Soft tissue tumor pathology: New diagnostic immunohistochemical markers
Doyle, L. A. (2015) · Seminars in Diagnostic Pathology · doi:10.1053/j.semdp.2015.02.012 · Cited by 7 · see citing works
Zhang, M., Wang, X., Zhao, J., Yan, J., He, X., Qin, D., Liang, F., Tong, K., & Wang, J. (2023) · Molecular Biotechnology · doi:10.1007/s12033-023-00812-0 · Cited by 7 · see citing works
Kaur, H., Kala, S., Sood, A., Mridha, A. R., Kakkar, A., Yadav, R., Mishra, S., & Mishra, D. (2022) · Head and Neck Pathology · doi:10.1007/s12105-022-01434-9 · Cited by 6 · see citing works
Abtahi, J., & Ajan, A. (2018) · The Open Dentistry Journal · doi:10.2174/1874210601812011059 · Cited by 5 · see citing works
Toya, M., Yamada, Y., Yokoyama, R., Taguchi, K., Nabeshima, K., Isayama, T., & Oda, Y. (2020) · Pathology - Research and Practice · doi:10.1016/j.prp.2020.152832 · Cited by 5 · see citing works
Pathology of pleomorphic/undifferentiated and dedifferentiated bone neoplasms
Brčić, I., & Rosenberg, A. E. (2021) · Seminars in Diagnostic Pathology · doi:10.1053/j.semdp.2021.04.005 · Cited by 5 · see citing works
Pediatric Chondromyxoid Fibroma-Like Osteosarcoma
Stark, M. W., Heinrich, S. D., Raju, S., Mackey, D., Wasilewska, E. M., & Craver, R. D. (2016) · Fetal and Pediatric Pathology · doi:10.1080/15513815.2016.1259376 · Cited by 5 · see citing works
Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma
Shi, Y., Wang, Z., Shao, Y., Guang, Q., Zhang, J., Liu, B., Wu, C., Wang, Y., & Sui, P. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149808 · Cited by 4 · see citing works
A rare rib lesion due to parosteal osteosarcoma: a case report
Tözüm, H., Aydemir, A. N., Demiroğlu, M., Özkan, K., Ceyran, A. B., & Kılıç, B. (2019) · Journal of Medical Case Reports · doi:10.1186/s13256-018-1958-7 · Cited by 4 · see citing works
Chen, C., He, X., Chen, M., Du, T., Qin, W., Jing, W., & Zhang, H. (2023) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-023-03530-9 · Cited by 3 · see citing works
Multifocal low-grade central osteosarcoma: a rare case
Boyle, R., Giuffrè, B., & Bonar, S. F. (2016) · Skeletal Radiology · doi:10.1007/s00256-016-2384-9 · Cited by 3 · see citing works
Pinieux, G. D. B. D., Gomez‐Brouchet, A., & Bouvier, C. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-416721-6.00024-8 · Cited by 3 · see citing works
Jeong, H. S., Lee, S. K., Kim, J.-Y., Yoo, C., & Joo, M. W. (2025) · Diagnostics · doi:10.3390/diagnostics15243120 · Cited by 2 · see citing works
Farshid, G., Otto, S., Collis, M., Napper, S., & Nicola, M. (2023) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000001098 · Cited by 2 · see citing works
Recurrent cementoblastoma with multifocal growth and cellular atypia: a case report
Oya, K., Takeshita, A., Wakamori, K., Song, M., Kimura, H., Hirose, K., Shimamoto, H., Sato, S., Matsunaga, K., Uzawa, N., et al. (2024) · Diagnostic Pathology · doi:10.1186/s13000-024-01479-0 · Cited by 2 · see citing works
Tabareau-Delalande, F., & Pinieux, G. D. B. D. (2016) · Current Oral Health Reports · doi:10.1007/s40496-016-0086-y · Cited by 2 · see citing works
Protocolo para el estudio de muestras y estandarización del informe patológico de tumores óseos
Machado, I., Pozo‐Kreilinger, J. J., Marcilla, D., Cruz, J., Tardío, J. C., Astudillo, A., & Bagué, S. (2016) · Revista Española de Patología · doi:10.1016/j.patol.2016.08.003 · Cited by 2 · see citing works
Polμ deficiency induces moderate shortening of P53−/− mouse lifespan and modifies tumor spectrum
Escudero, B., Herrero, D., Torres, Y., Cañón, S., de Molina-Iracheta, A., Carmona, R. M., Suela, J., Blanco, L., Samper, E., & Bernad, A. (2017) · DNA repair · doi:10.1016/j.dnarep.2017.04.001 · Cited by 2 · see citing works
Dedifferentiation in low-grade osteosarcoma: a Japanese Musculoskeletal Oncology Group (JMOG) study
Hirai, T., Kobayashi, H., Kobayashi, E., Saito, M., Akiyama, T., Kikuta, K., Nakai, T., Endo, M., Tsukamoto, S., Hakozaki, M., et al. (2022) · International Journal of Clinical Oncology · doi:10.1007/s10147-022-02223-8 · Cited by 2 · see citing works
Nodomi, S., Umeda, K., Okamoto, T., Saida, S., Hiramatsu, H., Watanabe, K., Adachi, S., & Heike, T. (2016) · Pediatric Blood & Cancer · doi:10.1002/pbc.26052 · Cited by 2 · see citing works
Two cases of parosteal osteosarcoma with unusual histological and molecular features
Farah, B. L., & Sittampalam, K. (2020) · Pathology · doi:10.1016/j.pathol.2020.08.018 · Cited by 2 · see citing works
Tsukamoto, S., Righi, A., Mavrogenis, A. F., Masunaga, T., Honoki, K., Fujii, H., Kido, A., Tanaka, Y., Tanaka, Y., & Errani, C. (2024) · MUSCULOSKELETAL SURGERY · doi:10.1007/s12306-024-00821-5 · Cited by 1 · see citing works
Sinonasal Specific Bone Lesions, Including Fibro-Osseous and Select Odontogenic Lesions
Torres, J. M. V., & Kerr, D. A. (2024) · Surgical pathology clinics · doi:10.1016/j.path.2024.08.001 · Cited by 1 · see citing works
Saoud, C., Zhang, Y., Benhamida, J. K., Villafania, L. B., Gundem, G., Cimera, R., Sinchun, H., Shukla, N. N., Reed, D. R., Papaemmanouil, E., et al. (2025) · Modern Pathology · doi:10.1016/j.modpat.2025.100931 · Cited by 1 · see citing works
de la Guardia, V., O’Meally, A. A., Gambarotti, M., Spinnato, P., Frisoni, T., Cocchi, S., Magagnoli, G., Ibrahim, T., Benini, S., Pacheco, M., et al. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154326 · Cited by 1 · see citing works
Chiu, C.-Y., Lin, T.-P., Hang, J., Huang, H.-E., Kao, T.-H., & Shen, S. (2023) · Radiology Case Reports · doi:10.1016/j.radcr.2023.11.085 · Cited by 1 · see citing works
Tallegas, M., Gomez‐Brouchet, A., Legrand, M., Bouvier, C., & Pinieux, G. D. B. D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821666-8.00017-7 · Cited by 1 · see citing works
Inwards, C. Y., & Wenger, D. E. (2015) · Springer eBooks · doi:10.1007/978-1-4471-6578-1_13 · Cited by 1 · see citing works
Bone Tumours - A Comprehensive Review of Selected Topics
Amarasekera, H. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.100923
Perspective Chapter: Osteosarcomas of the Head and Neck
Plass, I. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.107456 · Cited by 1 · see citing works
Tumor Markers in Common Oral and Maxillofacial Lesions
Azizi, T. (2015) · InTech eBooks · doi:10.5772/59342
Fujihara, S., Yamasaki, T., Shimokawa, K., & Yoon, H. (2016) · Open Journal of Pathology · doi:10.4236/ojpathology.2016.61003
Molecular Pathogenesis of Bone Tumours
Smolle, M. A., & Haybaeck, J. (2017) · Springer eBooks · doi:10.1007/978-3-319-53661-3_3
Werner, M. (2015) · Springer eBooks · doi:10.1007/978-3-642-04566-0_47
Nielsen, G. P., Rosenberg, A. E., Deshpande, V., Hornicek, F. J., Kattapuram, S. V., & Rosenthal, D. I. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-47777-2.50013-6
Inwards, C. Y., & Wenger, D. E. (2020) · Springer eBooks · doi:10.1007/978-3-030-28315-5_15
Molecular genetics of bone tumors
Agaram, N. P. (2022) · Diagnostic histopathology · doi:10.1016/j.mpdhp.2022.09.004
(2021) · American Registry of PathologyArlington, Virginia eBooks · doi:10.55418/9781933477138-05
Synchronous Low-Grade Central Osteosarcoma and Ewing Sarcoma: A Rare Case Report
Christensen, D., Belair, J. A., Basu-Mallick, A., Brown, S., Klein, M. J., & Jiang, W. (2024) · International Journal of Surgical Pathology · doi:10.1177/10668969241239675
Nonodontogenic Intraosseous Tumors
(2017) · Elsevier eBooks · doi:10.1016/b978-0-323-39054-5.00017-5
Osteitis in long bones of SAPHO syndrome mimicking osteosarcoma
Cui, R., & Dai, S. (2024) · Lara D. Veeken · doi:10.1093/rheumatology/keae241
Kattoor, J., Sindhu Nair, P., & Geothe, J. (2024) · Springer eBooks · doi:10.1007/978-981-99-4738-6_5
Montag, A. (2016) · Elsevier eBooks · doi:10.1016/b978-1-4160-5768-0.00008-1
González-López, J., González‐Rojo, P., Berenguer-Rubio, A., Casaní-Galdón, S., García, D., Valera, M. S., Vidal, A., Huart, M. C., Rangel, A., de la Calva, C., et al. (2026) · Revista Española de Patología · doi:10.1016/j.patol.2026.100881
- Authors
- Yoshida, A., Ushiku, T., Motoi, T., Beppu, Y., Fukayama, M., Tsuda, H., & Shibata, T.
- Affiliations
- National Cancer Center Hospital (JP)
- The University of Tokyo (JP)
- Tokyo Metropolitan Komagome Hospital (JP)
- National Cancer Center Research Institute (JP)
- Corresponding author
- Yoshida, Akihiko
- Tsuda, Hitoshi
- Shibata, Tatsuhiro
- Venue
- American Journal of Surgical Pathology
- Published
- 2012-03
- Volume
- 36
- Issue
- 3
- Pages
- 423-431
- ISSN
- 0147-5185 (ISSN-L)
- OpenAlex
- W2032358116
- Cited by
- 98
- References
- 31
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 9 · 2020: 5 · 2019: 7 · 2018: 10 · 2017: 5 · 2016: 12 · 2015: 9 · 2014: 9 · 2013: 3
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Surgical Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21590386)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- high-grade osteosarcoma, low-grade osteosarcoma, MDM2, CDK4, gene amplification, tumor subclassification, parosteal osteosarcoma, immunohistochemical markers
- MeSH terms
- Adolescent, Adult, Aged, Biopsy, Bone Neoplasms, Child, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Recurrence, Local, Predictive Value of Tests, Prognosis, Retrospective Studies, Osteosarcoma, Biomarkers, Tumor, Cyclin-Dependent Kinase 4, Proto-Oncogene Proteins c-mdm2, Cell Dedifferentiation, Young Adult, Neoplasm Grading, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
