Bone and soft tissue sarcomas, tumors of the skinBone and soft tissue sarcomas, tumors of the skinСаркомы костей, мягких тканей и опухоли кожи2219-46142782-3687Publishing House ABV Press298EXPERIMENTAL ONCOLOGYЭКСПЕРИМЕНТАЛЬНАЯ ОНКОЛОГИЯMOLLECULAR AND BIOLOGIC MARKERS EXPRESSION IN CHONDROSARCOMAS AND ITS CORRELATION WITH CLINICAL AND MORPHOLOGICAL CHARACTERISTICS AND DESEASE OUTCOMEЭКСПРЕССИЯ МОЛЕКУЛЯРНО-БИОЛОГИЧЕСКИХ МАРКЕРОВ В ХОНДРОСАРКОМАХ, ИХ СВЯЗЬ С ОСНОВНЫМИ КЛИНИКОМОРФОЛОГИЧЕСКИМИ ХАРАКТЕРИСТИКАМИ ОПУХОЛИ И ПРОГНОЗОМBoulytchevaI. V.БулычеваИ. В.
Russian Federation
irena@boulytcheva.comSolovievYu. N.СоловьевЮ. Н.
Russian Federation
KushlinskiyN. E.КушлинскийН. Е.
Russian Federation
AlievM. D.АлиевМ. Д.
Russian Federation
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical ScienceРоссийский онкологический научный центр имени Н.Н. Блохина РАМН1111201244596511012022Copyright ©; 2012, Boulytcheva I.V., Soloviev Y.N., Kushlinskiy N.E., Aliev M.D.Copyright ©; 2012, Булычева И.В., Соловьев Ю.Н., Кушлинский Н.Е., Алиев М.Д.2012Boulytcheva I.V., Soloviev Y.N., Kushlinskiy N.E., Aliev M.D.Булычева И.В., Соловьев Ю.Н., Кушлинский Н.Е., Алиев М.Д.https://creativecommons.org/licenses/by/4.0https://sarbon.abvpress.ru/jour/article/view/298

We retrospectively reviewed 39 patients with chondrosarcomas of different grades and 10 patients with benign cartilaginous tumors from 2000 through 2011. The mean age of the patients was 38 years (range, 24-72 years) with a predilection for men (24/14 in chondrosarcomas). The minimum follow-up was 0,6 year. All patients underwent modern surgical treatment in N.N. Blokhin Cancer Research Centre, Moscow, Russia with incorporation of CT and MRI for details before and after the operation. To perform immunohistochemical study (MMP-1, 2, 9, TIMP-1, Coll-IV, COX-2, Bcl-2, Bax) we choose 39 cases of chondrosarcomas with aggressive radiographic, and (or) morphologic behavior. Local recurrence and metastases were rare in long bones and more common in axial skeleton. The prognostic factors that determine the outcome were related to anatomic site, tumor size, and adequacy of treatment. Multidisciplinary approach in diagnoses is mandatory. Over expression of Bax, MMP-1 and MMP-9 >40% is a marker for altered cell phenotype and more aggressive behavior of the tumor. Local recurrence and potential metastasis are low in the group of low grade (grade 1) chondrosarcomas. To better classify these lesions multidisciplinary approach is necessary. Radiographic criteria, morphology and immunohistochemistry help to tailor less aggressive surgical procedure without compromising the results of the treatment.

В большинстве хондросарком обнаружена экспрессия MMP-1 (84,6%), MMP-2 (71,8%), MMP-9 (97,4%), TIMP-1 (82,3%), Coll-IV - (67,7%), COX-2 (72,2%), Bcl-2 (72,2%), Bax (84,2%). Высокие уровни экспрессии ММР-1 в хондросаркомах достоверно связаны с показателями безрецидивной и общей выживаемости, а Bax - с безрецидивной выживаемостью. Риск рецидива хондросаркомы наибольший при сочетании критерия Т3 с высоким уровнем экспрессии белка ММР-9 в опухоли.

TIMP-1Coll-IVCOX-2Bcl-2Baxchondrosarcomaatypical chondromaexpression MMP-1TIMP-1Coll-IVCOX-2Bcl-2Baxхондросаркомаатипическая хондромаэкспрессия MMP-1ММР-2ММР-9ММР-2ММР-9Алиев М.Д. Злокачественные опухоли костей. М., Издательская группа РОНЦ им. Н.Н. Блохина РАМН. 2008, 408 с.Bridge J.A., Bhatia P.S., Anderson J.R., Neff J.R. Biologic and clinical significance of cytogenetic and molecular cytogenetic abnormalities in benign and malignant cartilaginous lesions. Cancer Genet. Cytogenet. 1993, v. 69, p. 79-90.Bjornsson J., McLeod R.A., Unni K.K. et al. Primary chondrosarcoma of long bones and limb girdles. Cancer. 1998, v. 83, p. 2105-2119.Rodgers U.R., Kevorkian L., Surridge A.K. et al. Expression and function of matrix metalloproteinase (MMP)-28. Matrix Biology. 2009, v. 28, No. 5, p. 263-272.Dornauer K., Soder S., Inwards C.Y Matrix biochemistry and cell biology of dedifferentiated chondrosarcomas. Pathology Internat. 2010, v. 60, p. 365-372.Berend K.R., Toth A.P., Harrelson J.M. et al. Association between Ratio of Matrix Mettaloproteinase1 to Tissue Inhibitor of Metalloproteinase1 and Local Recurrence, Metastasis, and Survival in Human Chondrosarcoma. J. Bone and Joint Surg. 1998, v. 80A, No. 1, p. 1117.Aigner T., Dertinger S., Vornehm S. et al. Phenotypic diversity of neoplasti chondrocytes and extracellular matrix gene expression in cartilaginous neoplasms. Am. J. Pathol. 1997, v. 150, p. 2133-2141.Galbavy S., Lukac L., Porubsky J. et al. Collagen type IV in epithelial tumors of colon. Acta Histochem. 2002, v. 104, No. 4, p. 331-334.Yang E., Korsmeyer S.J. Molecular atopsis: a discourse on the Bcl2 family and cell death. Blood. 1996, v. 88, p. 386-401.Deveraux Q.L., Reed J.C. IAP family proteins suppressors of apoptosis. Genes Dev. 1999, v. 13, p. 239-252.Ferreira C.G., Epping M., Kruyt F.A. et al. Apoptosis: target of cancer therapy. Clin. Cancer Res. 2002, v. 8, p. 2024-2034.Bovee J.V., van den Broek L.J., Cleton Jansen A.M., Hogendoorn P.C. Upregulation of PTHrP and Bcl2 expression characterizes the progression of osteochondroma towards peripheral chondrosarcoma and is a late event in central chondrosarcoma. Lab. Invest. 2000, v. 80, p. 1925-1934.Amling M., Posl M., Hentz M.W. et al. PTHrP and Bcl-2: essential regulatory molecules in chondrocyte differentiation and chondrogenic tumors. Verh. Dtsch. Ges. Pathol. 1998, v. 82, p. 160-169.Rozeman L.B., Hameetman L., Cleton-Jansen A.M. et al. Absence of IHH and retention of PTHrP signaling in enchonromas and central chondrosarcomas. J. Pathol. 2005, v. 205, p. 476-482.Smith W.L., DeWitt D.L., Garavito R.M. Cyclooxygenases: structural, cellular, and molecular biology. Ann. Rev. Biochem. 2000, v. 69, p. 145-182.Pilbeam C.C., Harrison J.R., Raisz L.G. Prostaglandins and bone metabolism. In: Bilezikian J.P., Raisz L.G., Rodan G.A., editors. Principles of bone biology. New York: Academic Press. 2002, p. 979-994.Endo M., Matsumura T., Yamagichi T. et al. Cyclooxygenase-2 overexpression associated with a poor prognosis in chondrosarcomas. Hum. Pathol. 2006, v. 37, No. 4, p. 471-476.Кушлинский Н.Е. Молекулярно-биологические исследования при опухолях костей. В кн.: «Злокачественные опухоли костей» (под ред. М.Д. Алиева). М., Издательская группа РОНЦ им. Н.Н. Блохина РАМН. 2008, с. 19-54.Mandahl N., Gustafson P., Mertens F. et al. Cytogenetic aberrations and their prognostic impact in chondrosarcoma. Genes Chromosomes Cancer. 2002, v. 33, p. 188-200.Naumov V., Generozov E., Kushlinskiy N. Genotyping of candidate single nucleotide polymorphisms associated with osteosarcoma in a group of patients with various bone tumors. In abstracts of 25th Annual Meeting of the European MusculoSkeletal Oncology Society (May 15-16, 2012, Bologna, Italy Instituto Ortopedico Rizzoli). Bologna. 2012, p. 148.