Potential role of BCL2 in the recurrence of uterine smooth muscle tumors of uncertain malignant potential

Conconi,Donatella; Chiappa,Valentina; Perego,Patrizia; Redaelli,Serena; Bovo,Giorgio; Lavitrano,Marialuisa; Milani,Rodolfo; Dalprà,Leda; Lissoni,Andrea Alberto

doi:10.3892/or.2016.5274

Potential role of BCL2 in the recurrence of uterine smooth muscle tumors of uncertain malignant potential

Authors:
- Donatella Conconi
- Valentina Chiappa
- Patrizia Perego
- Serena Redaelli
- Giorgio Bovo
- Marialuisa Lavitrano
- Rodolfo Milani
- Leda Dalprà
- Andrea Alberto Lissoni
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Affiliations: School of Medicine and Surgery, University of Milano-Bicocca, I-20900 Monza, Italy, Department of Obstetrics and Gynecology, San Gerardo Hospital, I-20900 Monza, Italy, Unit of Pathology, San Gerardo Hospital, I-20900 Monza, Italy
Published online on: November 24, 2016 https://doi.org/10.3892/or.2016.5274
Pages: 41-47
Copyright: © Conconi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Uterine smooth muscle tumors are the most common female genital tract neoplasms. While leiomyosarcoma has been studied at length, smooth muscle tumors of uncertain malignant potential (STUMPs) still have ambiguous and unresolved issues, with a risk of relapse and evolution largely undefined. We performed an array comparative genomic hybridization analysis on a primitive STUMP and its local recurrence, histologically diagnosed as undifferentiated sarcoma. To the best of our knowledge, our report is the first genomic study on primitive STUMPs and the different relapsed tumors. The results showed few copy number alterations shared between both samples and the high heterogeneity in the STUMP was apparently lost in the sarcoma. Surprisingly the STUMP presented an amplification of the BCL2 gene, not observed in the relapsed tumor. Additionally, fluorescence in situ hybridization and immunohistochemical staining were performed to confirm BCL2 amplification and expression in these samples and in two other cases of primitive STUMPs and their corresponding relapsed tumors. The presence of BCL2 in multiple copies and expression in the two primitive STUMPs and two relapsed tumors was confirmed. The marked amplification of the BCL2 gene present in the primitive STUMP and the multiple copies also observed in other cases, suggest its potential role as a marker of STUMP malignant potential and recurrence.

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1	Zhai YL, Nikaido T, Toki T, Shiozawa A, Orii A and Fujii S: Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus. Br J Cancer. 80:1658–1664. 1999. View Article : Google Scholar : PubMed/NCBI
2	Kotsopoulos IC, Barbetakis N, Asteriou C and Voutsas MG: Uterine smooth muscle tumor of uncertain malignant potential: A rare cause of multiple pulmonary nodules. Indian J Med Paediatr Oncol. 33:176–178. 2012. View Article : Google Scholar : PubMed/NCBI
3	Ip PP, Cheung AN and Clement PB: Uterine smooth muscle tumors of uncertain malignant potential (STUMP): A clinicopathologic analysis of 16 cases. Am J Surg Pathol. 33:992–1005. 2009. View Article : Google Scholar : PubMed/NCBI
4	Hewedi IH, Radwan NA and Shash LS: Diagnostic value of progesterone receptor and p53 expression in uterine smooth muscle tumors. Diagn Pathol. 7:12012. View Article : Google Scholar : PubMed/NCBI
5	Copland JA, Luxon BA, Ajani L, Maity T, Campagnaro E, Guo H, LeGrand SN, Tamboli P and Wood CG: Genomic profiling identifies alterations in TGFβ signaling through loss of TGFβ receptor expression in human renal cell carcinogenesis and progression. Oncogene. 22:8053–8062. 2003. View Article : Google Scholar : PubMed/NCBI
6	Dong M, How T, Kirkbride KC, Gordon KJ, Lee JD, Hempel N, Kelly P, Moeller BJ, Marks JR and Blobe GC: The type III TGF-β receptor suppresses breast cancer progression. J Clin Invest. 117:206–217. 2007. View Article : Google Scholar : PubMed/NCBI
7	Turley RS, Finger EC, Hempel N, How T, Fields TA and Blobe GC: The type III transforming growth factor-β receptor as a novel tumor suppressor gene in prostate cancer. Cancer Res. 67:1090–1098. 2007. View Article : Google Scholar : PubMed/NCBI
8	Liu XL, Xiao K, Xue B, Yang D, Lei Z, Shan Y and Zhang HT: Dual role of TGFBR3 in bladder cancer. Oncol Rep. 30:1301–1308. 2013.PubMed/NCBI
9	Luan SL, Boulanger E, Ye H, Chanudet E, Johnson N, Hamoudi RA, Bacon CM, Liu H, Huang Y, Said J, et al: Primary effusion lymphoma: Genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration. J Pathol. 222:166–179. 2010. View Article : Google Scholar : PubMed/NCBI
10	Mataki H, Enokida H, Chiyomaru T, Mizuno K, Matsushita R, Goto Y, Nishikawa R, Higashimoto I, Samukawa T, Nakagawa M, et al: Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C. J Hum Genet. 60:53–61. 2015. View Article : Google Scholar : PubMed/NCBI
11	Petrini I, Meltzer PS, Zucali PA, Luo J, Lee C, Santoro A, Lee HS, Killian KJ, Wang Y, Tsokos M, et al: Copy number aberrations of BCL2 and CDKN2A/B identified by array-CGH in thymic epithelial tumors. Cell Death Dis. 3:e3512012. View Article : Google Scholar : PubMed/NCBI
12	Panzeri E, Conconi D, Antolini L, Redaelli S, Valsecchi MG, Bovo G, Pallotti F, Viganò P, Strada G, Dalprà L, et al: Chromosomal aberrations in bladder cancer: Fresh versus formalin fixed paraffin embedded tissue and targeted FISH versus wide microarray-based CGH analysis. PLoS One. 6:e242372011. View Article : Google Scholar : PubMed/NCBI
13	Silvestrini R, Veneroni S, Daidone MG, Benini E, Boracchi P, Mezzetti M, Di Fronzo G, Rilke F and Veronesi U: The Bcl-2 protein: A prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients. J Natl Cancer Inst. 86:499–504. 1994. View Article : Google Scholar : PubMed/NCBI
14	Alderson LM, Castleberg RL, Harsh GR IV, Louis DN and Henson JW: Human gliomas with wild-type p53 express bcl-2. Cancer Res. 55:999–1001. 1995.PubMed/NCBI
15	Fontanini G, Vignati S, Bigini D, Mussi A, Lucchi M, Angeletti CA, Basolo F and Bevilacqua G: Bcl-2 protein: A prognostic factor inversely correlated to p53 in non-small-cell lung cancer. Br J Cancer. 71:1003–1007. 1995. View Article : Google Scholar : PubMed/NCBI
16	Kaklamanis L, Savage A, Whitehouse R, Doussis-Anagnostopoulou I, Biddolph S, Tsiotos P, Mortensen N, Gatter KC and Harris AL: Bcl-2 protein expression: Association with p53 and prognosis in colorectal cancer. Br J Cancer. 77:1864–1869. 1998. View Article : Google Scholar : PubMed/NCBI
17	Yip KW and Reed JC: Bcl-2 family proteins and cancer. Oncogene. 27:6398–6406. 2008. View Article : Google Scholar : PubMed/NCBI
18	Scarfò L and Ghia P: Reprogramming cell death: BCL2 family inhibition in hematological malignancies. Immunol Lett. 155:36–39. 2013. View Article : Google Scholar : PubMed/NCBI
19	Talaiezadeh A, Jalali F, Galehdari H and Khodadadi A: Time depended Bcl-2 inhibition might be useful for a targeted drug therapy. Cancer Cell Int. 15:1052015. View Article : Google Scholar : PubMed/NCBI
20	Fischer H, Stenling R, Rubio C and Lindblom A: Colorectal carcinogenesis is associated with stromal expression of COL11A1 and COL5A2. Carcinogenesis. 22:875–878. 2001. View Article : Google Scholar : PubMed/NCBI
21	Wang LH, Xiang J, Yan M, Zhang Y, Zhao Y, Yue CF, Xu J, Zheng FM, Chen JN, Kang Z, et al: The mitotic kinase Aurora-A induces mammary cell migration and breast cancer metastasis by activating the Cofilin-F-actin pathway. Cancer Res. 70:9118–9128. 2010. View Article : Google Scholar : PubMed/NCBI
22	Stadler ZK, Esposito D, Shah S, Vijai J, Yamrom B, Levy D, Lee YH, Kendall J, Leotta A, Ronemus M, et al: Rare de novo germline copy-number variation in testicular cancer. Am J Hum Genet. 91:379–383. 2012. View Article : Google Scholar : PubMed/NCBI
23	Mudduluru G, Vajkoczy P and Allgayer H: Myeloid zinc finger 1 induces migration, invasion, and in vivo metastasis through Axl gene expression in solid cancer. Mol Cancer Res. 8:159–169. 2010. View Article : Google Scholar : PubMed/NCBI