The Expression of C-myc, Tenascin and HER-2/neu in Uterine Sarcomas and its Relation to Clinical Outcome

Zusammenfassung

Einführung: Grund für diese Studie war die Messung der Expression der Onkogene C-myc, HER-2/neu und das extra zelluläre Matrixglukoprotein Tenascin in Uterussarkomen in Bezug auf den klinischen Verlauf (Überlebens- und Rezidiv-Raten) zu untersuchen. Patienten und Methoden: 36 Patientinnen mit Uterussarkomen nahmen an der Studie teil, wobei 22 an einen Müller'schen Mischtumor, 10 an Leiomysarkom und 4 an anderen Sarkomarten erkrankt waren. C-myc, Tenascin und HER-2/neu Expression wurde in allen 36 Fällen mittels immunhistochemischer Methoden bestimmt. Ergebnisse: C-myc war in 23 von 36 Fällen (64%), Tenascin in 15 von 36 Fällen (42%) und HER-2/neu in 8 von 36 Fällen (22%) positiv. Überlebens- und Rezidivraten unterschieden sich nicht signifikant bezüglich positiver und negativer Expression bei allen 3 getesteten Substraten in dieser Studie. Schlussfolgerung: Bei den 36 Uterussarkomen dieser Studie (22 Müller'sche Mischtumore, 10 Leiomysarkome und 4 andere Sarkome) war die untersuchte Expression von 3 Proteinen nicht mit einer erhöhten oder verminderten Überlebens- oder Redzidiv-Rate assoziiert.

Abstract

Introduction: The purpose of this study was to evaluate the expression of oncogenes C-myc, HER-2/neu and the extracellular matrix glucoprotein Tenascin in uterine sarcomas and its relation to clinical outcome (survival and recurrence rates). Patients or Methods: 36 patients with uterine sarcomas participated in the study, where 22 suffered from mixed mullerian tumors, 10 from leiomyosarcoma and 4 from other types. C-myc, Tenascin and HER-2/neu expression was evaluated in all 36 cases by the use of immunochistochemical procedures. Results: C-myc was positive in 23 out at 36 cases (64 %), Tenascin in 15 out at 36 cases (42 %), and HER/2-neu in 8 out at 36 cases (22 %). Survival and recurrence rates were not found to differ significantly between positive or negative expression of all three substances of our study. Conclusion: In the 36 uterine sarcomas of the present study (22 mixed mullerian tumors, 10 leiomyosarcomas and 4 other types), expression of any of the 3 proteins investigated is not associated with increased/decreased survival or recurrence.

Schlüsselwörter

C-myc - HER-2/neu - Tenascin - Überlebens- und Rezidivraten - Immunhistochemie

Key words

C-myc - HER-2/neu - Tenascin - survival and recurrence rates - immunohistochemistry

References

• 1 Harlow B L, Weiss N S, Lofton S. The epidemiology of sarcomas of the uterus.  J Natl Cancer Inst. 1986;  76 399-402
• 2 Jemal A, Taylor M, Samuels A. et al . Cancer statistics, 2003.  CA Cancer J Clin. 2003;  53 5-26
• 3 Nordal R R, Thoresen S O. Uterine saromas in Norway 1956 - 1992; incidence, survival and mortality.  Eur J Cancer. 1997;  33 907-911
• 4 Olah K S, Dunn J A, Gee H. Leiomyosarcomas have a poorer prognosis than mixted mesodermal tumours when adjusting for known prognostic factors: the result of a retrospective study of 423 cases of uterine sarcoma.  Br J Obstet Gynaecol. 1992;  99 590-594
• 5 Echt G, Jepson J, Steel J. et al . Treatment of uterine sarcomas.  Cancer. 1990;  66 35-39
• 6 Doss L L, Llorens A S, Henriquez E M. Carcinosarcoma of the uterus: α 40-year experience from the state of Missouri.  Gynecol Oncol. 1984;  18 43-53
• 7 Ronnett B M, Zaino R J, Ellenson L H. et al .Endometrial cancer. Kurman RJ Blaustein’s Pathology of the Female Genital Tract New York; Springer 2002 5th ed: 501-560
• 8 Bartsich E G, Bowe E T, Moore J G. Leiomyosarcoma of the uterus.  Obstet Gynecol. 1968;  32 101-106
• 9 Giuntoli R L, Metzinger D S, Di Marco C S. et al . Retrospective review of 208 patients with leiomyosarcoma of the uterus: prognostic indicators, surgical management, and adjuvant therapy.  Gynecol Oncol. 2003;  89 460-469
• 10 Silverberg S G. Leiomyosarcoma of the uterus: a clinicopathologic study.  Obstet Gynecol. 1971;  28 613-628
• 11 Chang K L, Crabtree G S, Kim Lim-Tan S. et al . Primary uterine endometrial stromal neoplasms. A clinicipathologic study of 117 cases.  Am J Surg Pathol. 1990;  14 415-438
• 12 Larson B, Silfversword C, Nilsson B. et al . Mixed mullerian tumors of the uterus - prognostic factors: a clinical and histopathologic study of 147 cases.  Radiother Oncol. 1999;  21 123-132
• 13 Iwasa Z, Haga H, Konishi I. et al . Prognostic factors in uterine carcinosarcoma: a clinicopathologic study of 25 patients.  Cancer. 1998;  82 512-519
• 14 Berchuck A, Rubin S C, Hoskins W J. et al . Treatment of uterine leiomyosarcoma.  Obstet Cynecol. 1988;  71 845-854
• 15 Wolfson A H, Wolfson D J. et al . A multivariate analysis of clinicopathologic factors for predicting outcome in uterine sarcoma.  Gynecol Oncol. 1994;  52 56-61
• 16 Lennart K, Lennart B, Ulf S. et al . Flow cytometric analysis of uterine sarcomas.  Gynecol Oncol. 1994;  55 339-343
• 17 Nordal R R, Kristensen G B, Karen J. et al . The prognostic significance of surgery, tumor size, malignancy grade, menopausal status, and DNA ploidy in endometrial stromal sarcoma.  Gynecol Oncol. 1996;  62 254-259
• 18 Nordal R R, Kristensen G B, Stenwig A E. et al . An evaluation of prognostic factors in uterine carcinosarcoma.  Gynecol Oncol. 1997;  67 316-321
• 19 Seki A, Kodama J, Miyagi Y. et al . Amplification of the mdm-2 gene and p53 abnormalities in uterine sarcomas.  Int J Cancer. 1997;  26 33-37
• 20 Layfield L J, Liu K, Dodge R. et al . Uterine smooth muscle tumors: utility of classification by proliferation, ploidy, and prognostic markers vescus traditional histopathology.  Arch Pathol Lab Med. 2000;  124 221-227
• 21 Swisher E M, Gown A M, Skelly M. et al . The expression of epidermal growth factor receptor, HER-2/neu, p53, and Ki-67 antigen in uterine malignant mixed mesodermal tumors and adenosarcoma.  Gynecol Oncol. 1996;  60 81-88
• 22 Helman L J, Meltzer P. Mechanisms of sarcomas development.  Nat Rev Cancer. 2003;  3 685-694
• 23 Wang L, Felix J C, Lee J L. et al . The proto-oncogene c-Kit is expressed in leiomyosarcomas of the uterus.  Gynecol Oncol. 2003;  90 402-406
• 24 Raspollini M R, Susini T, Amunni G. et al . COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?.  Gynecol Oncol. 2005;  96 159-167
• 25 Horiuchi A, Nikaido T, Ito K. et al . Reduced expression of calponin h1 in leiomyosarcoma of the uterus.  Lab Invest. 1998;  78 839-846
• 26 Horiuchi A, Nikaido T, Taniguchi S. et al . Possible role of calponin h1 as a tumor suppressor in human uterine leiomyosarcoma.  J Natl Cancer Inst. 1999;  91 790-796
• 27 Ramondetta L M, Burke T W, Jhingran A. et al . Phase II trial of cisplatin, ifosfamide et mesna in patients with advanced or recurrent malignant mixed mullerian tumors with evaluation of potential molecular targets.  Gynecol Oncol. 2003;  90 529-536
• 28 Emoto M, Iwasaki H, Ishiguro M. et al . Angiogenesis in carcinosarcomas of the uterus: differences in the microvessel density and expression of vascular endothelial growth factor between the epithelial and mesenchymal elements.  Hum Pathol. 1999;  30 1232-1241
• 29 Roy R N, Gerulath A H, Cecutti A. et al . Loss of IGF-II imprinting in endometrial tumors: overexpression in carcinosarcoma.  Cancer Lett. 2000;  153 67-73
• 30 Borst M P, Baker V V, Dixon D. et al . Oncogene alterations in endometrial carcinoma.  Cancer Res. 1990;  38 364-366
• 31 Williams J A, Wang Z R, Parrish R S. et al . Fluorescence in situ hybridization analysis of HER-2/neu, C-myc, and p53 in endometrial cancer.  Exp Mol Pathol. 1999;  67 135-143
• 32 Monk B J, Chapman J A, Johnson G A. et al . Correlation of c-myc and HER-2/neu amplification and expression with histopathologic variables in uterine corpus cancer.  Am J Obstet Gynecol. 1994;  171 1193-1198
• 33 Kohn E C. Aging issue in invasion and metastasis.  Cancer. 1999;  71 552
• 34 Berchuck A, Rodriguez G, Kinney P B. et al . Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease.  Am J Obstet Gynecol. 1991;  164 17-21
• 35 Hetzel D J, Wilson T O, Keeney G L. et al . HER-2/neu expression: A major prognostic factor in endometrial cancer.  Cancer Res. 1992;  47 179-185
• 36 Lu K H, Bell D A, Welch W E. et al . Evidence for the multifocal origin of bilateral and advanced human serous borderline ovarian tumors.  Cancer Res. 1998;  58 2328-2330
• 37 Chert M A, Qi W N, Erickson H P. et al . Tenascin - C expression and distribution in cultured human chondrocytes and chodrosarcoma cells.  J Orthop Res. 2002;  20 834-841
• 38 Chert M A, Jung S T. et al . The clinical significance of Tenascin - C splice variant expression in chondrosarcoma.  Oncology. 2001;  61 306-314
• 39 Tanaka M, Yamazaki T, Araki N. Clinical significance of Tenascin-C expression in osteosarcoma: Tenascin-C promotes distant metastases of osteosarcoma.  Int J Mol Med. 2000;  5 505-510
• 40 Kostianovsky M, Greko M A, Gangiarella J. Tenascin-C expression in ultrastructurally defined angiogenic and vasculogenic lesions.  Ultrastruct Pathol. 1997;  21 537-544
• 41 Saxon B R, Brand R W, Han P. Cellular expression of adhesion factors in childhood rhabdomyosarcoma.  Pediatr Pathol Lab Med. 1997;  17 259-266
• 42 Guarino M, Reale D, Micoli G. The extracellular matrix in sarcomatoid carcinomas of the breast.  Virchows Arch A Pathol Anat Histopathol. 1993;  423 131-136
• 43 Ilmonen S, Jahkola T, Turunen J P. et al . Tenascin-C in primary malignant melanoma of the skin.  Histopathology. 2004;  45 450-411
• 44 Koljonen V, Jahkola T, Tukianen E. et al . Tenascin-C in primary Merkell cell carcinoma.  J Clin Pathol. 2005;  58 297-300
• 45 Chiouet-Ehrismann R. Tenascins.  Int J Biochem Cell Biol. 2004;  36 986-990
• 46 Kahn H J, Fekete E, From L. Tenascin differentiates dermatofibroma from dermatofibrosarcoma protuberans:comparison with CD34 and factor XIIIa.  Hum Pathol. 2001;  193 511-516
• 47 Lightner V A, Slemp C A, Erickson H P. Localization and quantitation of hexabrachion (Tenascin) in skin, embryonic brain, tumors, and plasma.  Ann NY Acad Sci. 1990;  580 260-275
• 48 Jeffers M D, Richmond J A, Macaulay E M. Overexpression of the c-myc proto-oncogene occurs frequently in uterine sarcomas.  Mod Pathol. 1995;  8 701-704
• 49 Emoto M, Iwasaki H, Oshima K. et al . Charasteristics of rhabdomyosarcoma cell lines derived from uterine carcinosarcomas.  Virchows Arch. 1997;  431 249-256
• 50 Fotiou S K, Tserkezoglou A J, Maher H. et al . Chromosome aberrations and expression of ras and myc oncogenes in leiomyomas and a leiomyosarcoma of the uterus.  Eur J Gynaecol Oncol. 1992;  13 340-345
• 51 Vollmer G, Lightner V A, Carter C A. et al . Localization of Tenascin in uterine sarcomas and partially transformed endometrial stromal cell.  Pathobiology. 1993;  61 67-76
• 52 Guarino M, Giordano F, Pallotti F. et al . Malignant mixed mullerian tumor of the uterus. Features favoring the origin from a common cell clone and an epithelial - to mesenchymal transformation mechanism of histogenesis.  Tumori. 1998;  84 391-397
• 53 Schnyder B, Semadeni R O, Fischer R W. et al . Distribution pattern of Tenascin-C in normal and neoplastic mesenchymal tissues.  Int J Cancer. 1997;  72 217-224
• 54 Amant F, Vloeberghs V, Woestenborghs H. et al . ERBB-2 gene overexpression and amplification in uterine sarcomas.  Gynecol Oncol. 2004;  95 583-587