ORIGINAL ARTICLE
Comprehensive immunohistochemical analysis based on the origin of leiomyosarcoma
1
Department of Pathology, Faculty of Medicine, Ondokuz Mayls University Samsun, Atakum/Samsun, Turkey
Submission date: 2022-03-18
Final revision date: 2022-06-30
Acceptance date: 2022-10-27
Publication date: 2023-01-10
Corresponding author
Deniz Bayçelebi
Deniz Bayçelebi, MD, PhD Department of Pathology Faculty of Medicine Ondokuz Mayls University Kurupelit campus 55200 Atakum/Samsun, Turkey
Deniz Bayçelebi, MD, PhD Department of Pathology Faculty of Medicine Ondokuz Mayls University Kurupelit campus 55200 Atakum/Samsun, Turkey
Pol J Pathol 2022;73(3):233-243
KEYWORDS
TOPICS
ABSTRACT
Diagnostic criteria, biological behavior, and treatment approaches of leiomyosarcomas (LMS) may differ according to the origin of the tumor. This is important in terms of patient’s management, especially in tumors located in the peritoneum and retroperitoneal sites. In our study, we aimed to demonstrate the immunophenotypic characteristics of uterine and extra-uterine LMS using a large antibody panel, and to determine whether they potentially play a role in the differences among these tumor groups.
Between 2006 and 2018, 29 uterine and 42 extra-uterine primary LMS were included in this study. Using tissue samples taken from the areas that best represented the tumor, an immunohistochemical study was performed on the blocks prepared by tissue micro-array method with estrogen and progesterone receptor (PR), WT-1, SMA, desmin, caldesmon, calponin, p16, p53, MDM2, CDK4, bcl-2, cyclin D1, fascin, EMMPRIN, FOXM1, c-erb-B2, c-Myc, PAX8, and CD117. Staining results of uterine and extra-uterine LMS were evaluated with these 20 antibodies.
In uterine LMS compared with extra-uterine LMS, estrogen receptor (48% vs. 12%), PR (62% vs. 21%), desmin (79% vs. 50%), and EMMPRIN (69% vs. 45%) staining rate was detected higher. In extra-uterine LMS, caldesmon (88% vs. 69%), c-Myc (33% vs. 10%), and cyclin D1 (52% vs. 28%) were stained higher than uterine LMS (p < 0.05). No significant staining difference was detected with other antibodies.
We concluded that estrogen receptor, PR, desmin, EMMPRIN, caldesmon, c-Myc, and cyclin D1 antibodies may help to determine primary origin of the tumor in LMS cases.
Between 2006 and 2018, 29 uterine and 42 extra-uterine primary LMS were included in this study. Using tissue samples taken from the areas that best represented the tumor, an immunohistochemical study was performed on the blocks prepared by tissue micro-array method with estrogen and progesterone receptor (PR), WT-1, SMA, desmin, caldesmon, calponin, p16, p53, MDM2, CDK4, bcl-2, cyclin D1, fascin, EMMPRIN, FOXM1, c-erb-B2, c-Myc, PAX8, and CD117. Staining results of uterine and extra-uterine LMS were evaluated with these 20 antibodies.
In uterine LMS compared with extra-uterine LMS, estrogen receptor (48% vs. 12%), PR (62% vs. 21%), desmin (79% vs. 50%), and EMMPRIN (69% vs. 45%) staining rate was detected higher. In extra-uterine LMS, caldesmon (88% vs. 69%), c-Myc (33% vs. 10%), and cyclin D1 (52% vs. 28%) were stained higher than uterine LMS (p < 0.05). No significant staining difference was detected with other antibodies.
We concluded that estrogen receptor, PR, desmin, EMMPRIN, caldesmon, c-Myc, and cyclin D1 antibodies may help to determine primary origin of the tumor in LMS cases.
REFERENCES (61)
1.
Chiang S, Oliva E. Recent developments in uterine mesenchymal neoplasms. Histopathology 2013; 62: 124-137.
2.
Crum CP, Nucci M, Howitt B, et al. Malignant leiomyosarcoma. In: Diagnostic gynecologic and obstetric pathology. Philadelphia, PA: Saunders/Elsevier 2017, 1737-58.
3.
Guo X, Jo VY, Mills AM, et al. Clinically relevant molecular subtypes in leiomyosarcoma. Clin Cancer Res 2015; 21: 3501-3511.
4.
Toledo G, Oliva E. Smooth muscle tumors of the uterus: a practical approach. Arch Pathol Lab Med 2008; 132: 595-605.
5.
Lamm W, Natter C, Sophie S, et al. Distinctive outcome in patients with non-uterine and uterine leiomyosarcoma. BMC Cancer 2014; 14: 981.
7.
Billings SD, Folpe AL, Weiss SW. Do leiomyomas of deep soft tissue exist? An analysis of highly differentiated smooth muscle tumors of deep soft tissue supporting two distinct subtypes. Am J Surg Pathol 2001; 25: 1134-1142.
8.
Horiuchi K, Yabe H, Mukai M, et al. Multiple smooth muscle tumors arising in deep soft tissue of lower limbs with uterine leiomyomas. Am J Surg Pathol 1998; 22: 897-901.
9.
Lee CH, Turbin da, Sung VYC, et al. A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors. Mod Pathol 2009; 22: 1519-1531.
10.
Paal E, Miettinen M. Retroperitoneal leiomyomas: a clinicopathologic and immunohistochemical study of 56 cases with a comparison to retroperitoneal leiomyosarcomas. Am J Surg Pathol 2001; 25: 1355-1363.
12.
Worhunsky DJ, Gupta M, Gholami S, et al. Leiomyosarcoma: one disease or distinct biologic entities based on site of origin? J Surg Oncol 2015; 111: 808-812.
13.
Bodner-Adler B, Bodner K, Czerwnka K, et al. Expression of p16 protein in patients with uterine smooth muscle tumors: an immunohistochemical analysis. Gynecol Oncol 2005; 96: 62-66.
14.
Miettinen M, Fetsch JF. Evaluation of biological potential of smooth muscle tumours. Histopathology 2006; 48: 97-105.
15.
Mittal K, Demopoulos RI. MIB-1 (Ki-67), p53, estrogen receptor, and progesterone receptor expression in uterine smooth muscle tumors. Hum Pathol 2001; 32: 984-987.
16.
O’Neill CJ, McBride HA, Connolly LE, et al. Uterine leiomyosarcomas are characterized by high p16, p53 and MIB1 expression in comparison with usual leiomyomas, leiomyoma variants and smooth muscle tumours of uncertain malignant potential. Histopathology 2007; 50: 851-858.
17.
Xiong L, Edwards CK, Zhou L. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature. Int J Mol Sci 2014; 15: 17411-1741.
18.
Thanopoulou E, Thway K, Khabra K, Judson I. Treatment of hormone positive uterine leiomyosarcoma with aromatase inhibitors. Clin Sarcoma Res 2014; 4: 5.
19.
Cui RR, Wright JD, Hou JY. Uterine leiomyosarcoma: a review of recent advances in molecular biology, clinical management and outcome. BJO 2017; 124: 1028-1037.
20.
Dei Tos AP, Maestro R, Doglioni C, et al. Tumor suppressor genes and related molecules in leiomyosarcoma. Am J Pathol 1996; 148: 1037-1045.
21.
Kawaguchi K, Oda Y, Saito T, et al. Mechanisms of inactivation of the p16INK4a gene in leiomyosarcoma of soft tissue: decreased p16 expression correlates with promoter methylation and poor prognosis. J Pathol 2003; 201: 487-495.
22.
Kefeli M, Ylldlz L, Kaya FC, et al. Fascin expression in uterine smooth muscle tumors. Int J Gynecol Pathol 2009; 28: 328-333.
23.
Makinen N, Vahteristo P, Kampjarvi K, et al. MED12 exon 2 mutations in histopathological uterine leiomyoma variants. Eur J Hum Genet, 2013; 21: 1300-1303.
24.
Markowski DN, Huhle S, Nimzyk R, et al. MED12 mutations occurring in benign and malignant mammalian smooth muscle tumors. Genes Chromosomes Cancer 2013; 52: 297-304.
25.
Longacre TA, Lim D, Parra-Herran C. Uterine Leiomyosarcoma. In: World Health Organization Classification of Tumors of Female Genital Tumors. Lyon, France: IARC Press 2020, 283-285.
26.
Dry SM, Fröhling S. Leiomyosarcoma. In: World Health Organization Classification of Tumors of Soft Tissue and Bone. Lyone, France: IARC Press 2020, 195-197 .
27.
Billings SD, Panagopoulos I, Leiomyoma. In: World Health Organization Classification of Tumors of Soft Tissue and Bone. Lyon, France: IARC Press 2020, 188-189.
28.
Folpe A, Eiston D, Kutzner H. Cutaneous leiomyosarcoma. In: World Health Organization Classification of Tumors of Skin Tumours. Lyone, France: IARC Press 2020, 330.
29.
Bodner K, Bodner-Adler B, Kimberger O, et al. Bcl-2 receptor expression in patients with uterine smooth muscle tumors: an immunohistochemical analysis comparing leiomyoma, uterine smooth muscle tumor of uncertain malignant potential, and leiomyosarcoma. J Soc Gynecol Investig 2004; 11: 187-191.
30.
De Graaff MA, de Rooij MAJ, van den Akker BEWM, et al. Inhibition of Bcl-2 family members sensitises soft tissue leiomyosarcomas to chemotherapy. Br J Cancer 2016; 114: 1219-1226.
31.
Kefeli M, Yildiz L, Gun S, et al. EMMPRIN (CD147) expression in smooth muscle tumors of the uterus. Int J Gynecol Pathol 2016; 35: 1-7.
32.
Maekawa A, Kohanshi K, Setsu N, et al. Expression of Forkhead box M1 in soft tissue leiomyosarcoma: clinicopathologic and in vitro study using a newly established cell line. Cancer Sci 2016; 107: 95-102.
33.
Oliva E, Young RH, Amin MB, et al. An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies. Am J Surg Pathol 2002; 26: 403-412.
34.
Özçelik B, Akgün H, SERiN IS et al. Uterin leiomyosarkomlarda C-kit pozitifliği ile Bcl-2 artlŞl araslndaki iliŞki. Türk Jinekolojik Onkoloji Dergisi 2004; 7: 59-65.
35.
Raspollini MR, Amunni G, Villanucci A, et al. c-Kit expression in patients with uterine leiomyosarcomas: a potential alternative therapeutic treatment. Clin Cancer Res 2004; 10: 3500-3503.
36.
Wang L, Felix JC, Lee JL, et al. The proto-oncogene c-kit is expressed in leiomyosarcomas of the uterus. Gynecol Oncol 2003; 90: 402-406.
37.
Yildiz L, Kefeli M, Aydln, O et al. Fascin expression in melanocytic lesions of the skin. Eur J Dermatol 2009; 19: 445-450.
38.
Zhai YL, Nikaido T, Toki T, et al. Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus. Br J Cancer 1999; 80: 1658-1664.
39.
Rao UN, Finkelstein SD, Jones MW. Comparative immunohistochemical and molecular analysis of uterine and extrauterine leiomyosarcomas. Modern Pathology 1999; 12: 1001-1009.
40.
Kelley TW, Borden EC, Goldblum JR. Estrogen and progesterone receptor expression in uterine and extrauterine leiomyosarcomas: an immunohistochemical study. Appl Immunohistochem Mol Morphol 2004; 12: 338-341.
41.
Carvalho JC, Thomas DG, Lucas DR. Cluster analysis of immunohistochemical markers in leiomyosarcoma delineates specific anatomic and gender subgroups. Cancer 2009; 115: 4186-4195.
42.
Bing Z, Pasha TL, Acs G, et al. Cytoplasmic overexpression of WT-1 in gastrointestinal stromal tumor and other soft tissue tumors. Appl Immunohistochem Mol Morphol 2008; 16: 316-321.
43.
Abeler VM, Nenodovic M. Diagnostic immunohistochemistry in uterine sarcomas: a study of 397 cases. Int J Gynecol Pathol 2011; 30: 236-243.
44.
Hisaoka M, Wei-Qui S, Morio, T et al. Specific but variable expression of h-caldesmon in leiomyosarcomas: an immunohistochemical reassessment of a novel myogenic marker. Appl Immunohistochem Mol Morphol 2001; 9: 302-308.
45.
Rangdaeng S, Truong LD. Comparative immunohistochemical staining for desmin and muscle-specific actin. A study of 576 cases. Am J Clin Pathol 1991; 96: 32-45.
46.
Demicco EG, Boland GM, Brewer Savannah KJ et al. Progressive loss of myogenic differentiation in leiomyosarcoma has prognostic value. Histopathology 2015; 66: 627-638.
47.
Jeffers MD, Richmond JA, Macaulay EM. Overexpression of the c-myc proto-oncogene occurs frequently in uterine sarcomas. Mod Pathol 1995; 8: 701-704.
48.
Tsiatis AC, Herceg ME, Keedy VL, et al. Prognostic significance of c-Myc expression in soft tissue leiomyosarcoma. Mod Pathol 2009; 22: 1432-1438.
49.
Hong A, Davies S, Steven G, et al. Cyclin D1 overexpression in AIDS-related and classic Kaposi sarcoma. Appl Immunohistochem Mol Morphol 2004; 12: 26-30.
50.
Horvai AE, Kramer MJ, O’Donnell R. Beta-catenin nuclear expression correlates with cyclin D1 expression in primary and metastatic synovial sarcoma: a tissue microarray study. Arch Pathol Lab Med 2006; 130: 792-798.
51.
Kim JK, Diehl JA. Nuclear cyclin D1: an oncogenic driver in human cancer. J Cell Physiol 2009; 220: 292-296.
52.
Lin L, Hicks D, Xu B, et al. Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma. Mod Pathol 2005; 18: 705-709.
53.
Maelandsmo GM, Berner JM, Florenes VA, et al. Homozygous deletion frequency and expression levels of the CDKN2 gene in human sarcomas – relationship to amplification and mRNA levels of CDK4 and CCND1. Br J Cancer 1995; 72: 393-398.
54.
Lee CH, Ali RH, Rouzbahman M, et al. Cyclin D1 as a diagnostic lmmunomarker for endometrial stromal sarcoma with YWHAE-FAM22 rearrangement. Am J Surg Pathol 2012; 36: 1562-1570.
55.
Anderson SE, Nonaka D, Chuai S, et al. p53, epidermal growth factor, and platelet-derived growth factor in uterine leiomyosarcoma and leiomyomas. Int J Gynecol Cancer 2006; 16: 849-853.
56.
Blom R, Guerrieri C, Stal O, et al. Leiomyosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases. Gynecol Oncol 1998; 68: 54-61.
57.
Hall KL, Teneriello MG, Taylor RR, et al. Analysis of Ki-ras, p53, and MDM2 genes in uterine leiomyomas and leiomyosarcomas. Gynecol Oncol 1997; 65: 330-335.
58.
Konomoto T, Fukuda T, Hayashi K, et al. Leiomyosarcoma in soft tissue: examination of p53 status and cell proliferating factors in different locations. Hum Pathol 1998; 29: 74-81.
59.
O’Reilly PE, Raab SS, Niemann TH, et al. p53, proliferating cell nuclear antigen, and Ki-67 expression in extrauterine leiomyosarcomas. Mod Pathol 1997; 10: 91-97.
60.
Kobayashi H, Uekuri C, Akasaka J, et al. The biology of uterine sarcomas: a review and update. Mol Clin Oncol 2013; 1: 599-609.
61.
Posligua L, Silva EG, Deavers MT, et al. Low-grade smooth muscle tumors of the primary and the secondary mullerian system: a proposed concept of multicentricity. Int J Gynecol Pathol 2012; 31: 547-555.
Share
RELATED ARTICLE
| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
