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01.09.2011 | Preclinical study

Molecular classification of breast phyllodes tumors: validation of the histologic grading scheme and insights into malignant progression

verfasst von: Mei Kim Ang, Aik Seng Ooi, Aye Aye Thike, Patrick Tan, Zhongfa Zhang, Karl Dykema, Kyle Furge, Bin Tean Teh, Puay Hoon Tan

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2011

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Abstract

Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the development of borderline and malignant phyllodes tumors in an Asian population, and to assess if genetic data supported the categorization of these tumors into the existing three grades of benign, borderline, and malignant. Expression profiling of 21 phyllodes tumors (6 benign, 10 borderline, 5 malignant) was performed using Affymetrix U133Plus 2.0 GeneChips^®. Gene expression among benign, borderline, and malignant tumors was compared and a 29 gene list was able to classify them according to their histologic grade. Among these 29 genes are those responsible for matrix formation, cell adhesion, epidermis formation, and cell proliferation. Comparative genomic microarray analysis showed that the most common chromosomal alteration associated with borderline and malignant tumors was 1q gain, and an increasing number of chromosomal changes was noted with increasing histological grade. Upregulation of HOXB13 was seen in malignant relative to borderline phyllodes tumors and further investigated by immunohistochemistry in a corresponding set of formalin-fixed, paraffin-embedded tumors. HOXB13 protein overexpression was found to be correlated with stromal hypercellularity and atypia (P = 0.03, P = 0.039, respectively) and may be implicated in the development of malignant phyllodes tumors.

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Rosen PP, Dershaw D, Liberman L (1999) Breast pathology. Lippincott, Williams and Wilkins, Philadelphia

Reinfuss M, Mitus J, Duda K et al (1996) The treatment and prognosis of patients with phyllodes tumor of the breast: an analysis of 170 cases. Cancer 77:910–916PubMedCrossRef

Pietruszka M, Banes L (1978) Cystosarcoma phyllodes: a clinicopathological analysis of 42 cases. Cancer 41:1974–1983PubMedCrossRef

Halverson JD, Hori-Rubaina JM (1974) Cystosarcoma phyllodes of the breast. Am Surg 40:295–301PubMed

Tan PH, Jayabaskar T, Chuah K-L, Lee H-Y, Tan Y, Hilmy M, Hung H, Selvarajan S, Bay B-H (2005) Phyllodes tumors of the breast—the role of pathologic parameters. Am J Clin Pathol 123:529–540PubMedCrossRef

Jones AM, Mitter R, Springall R, Graham T, Winter E, Gillat C, Hanby AM, The Phyllodes Tumour Consortium, Tomlinson IPM, Sawyer EJ (2008) A comprehensive genetic profile of phyllodes tumors of the breast detects important mutations, intra-tumoral genetic heterogeneity and new genetic changes on recurrence. J Pathol 214:533–544

Rooshdiya ZK, Scolyer RA, Tse GM, Tan PH, Putti TC, Lee CS (2009) Pathogenic mechanisms in the initiation and progression of mammary phyllodes tumours. Pathology 41:105–117CrossRef

Yonemori K, Hasegawa T, Shimizu C et al (2006) Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast. Pathol Res Pract 202(10):705–712PubMedCrossRef

Tse GM, Putti TC, Kung FY et al (2002) Increased p53 protein expression in malignant mammary phyllodes tumors. Mod Pathol 15(7):734–740PubMedCrossRef

10.

Gatalica Z, Finkelstein S, Lucio E et al (2001) p53 protein expression and gene mutation in phyllodes tumors of the breast. Pathol Res Pract 197(3):183–187PubMedCrossRef

11.

Sawyer EJ, Poulsom R, Hunt FT et al (2003) Malignant phyllodes tumors show stromal overexpression of c-myc and c-kit. J Pathol 200(1):59–64PubMedCrossRef

12.

Tan PH, Jayabaskar T, Yip G, Tan Y, Hilmy M, Selvarajan S, Bay BH (2005) p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study. Mod Pathol 18:1527–1530PubMedCrossRef

13.

Carvalho S, e Silva AO, Milanezi F, Ricardo S, Leitao D, Amendoeira I, Schmitt FC (2004) c-KIT and PDGFRA in breast phyllodes tumours: overexpression without mutations? J Clin Pathol 57:1075–1079PubMedCrossRef

14.

Kersting C, Kuijper A, Schmidt H et al (2006) Amplifications of the epidermal growth factor receptor gene (EGFR) are common in phyllodes tumors of the breast and are associated with tumor progression. Lab Invest 86(1):54–61PubMedCrossRef

15.

Tse GM, Lui PC, Vong JS, Lau KM, Putti TC, Karim R, Scolyer RA, Lee CS, Yu AM, Ng DC, Tse AK, Tan PH (2009) Increased epidermal growth factor receptor (EGFR) expression in malignant mammary phyllodes tumors. Breast Cancer Res Treat 114:441–448PubMedCrossRef

16.

Kuijper A, van der Groep P, van der Wall E, van Diest PJ (2005) Expression of hypoxia-inducible factor 1 alpha and its downstream targets in fibroepithelial tumors of the breast. Breast Cancer Res 7:R808–R818PubMedCrossRef

17.

Tse GM, Tsang AK, Putti TC, Scolyer RA, Lui PC, Law BK, Karim RZ, Lee CS (2005) Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours. J Clin Pathol 58:185–189PubMedCrossRef

18.

Tse GM, Wong FC, Tsang AK, Lee CS, Lui PC, Lo AW, Law BK, Scolyer RA, Karim RZ, Putti TC (2005) Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour. J Clin Pathol 58:600–604PubMedCrossRef

19.

Koo CY, Bay BH, Lui PC et al (2006) Immunohistochemical expression of heparan sulfate correlates with stromal cell proliferation in breast phyllodes tumors. Mod Pathol 19(10):1344–1350PubMedCrossRef

20.

Niezabitowski A, Lackowska B, Rys J et al (1001) Prognostic evaluation of proliferative activity and DNA content in the phyllodes tumor of the breast: immunohistochemical and flow cytometric study of 118 cases. Breast Cancer Res Treat 65(1):77–85CrossRef

21.

Tse GM, Lui PC, Lee CS, Kung FY, Scolyer RA, Law BK, Lau TS, Karim R, Putti TC (2004) Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: a multicenter study of 185 cases. Hum Pathol 35:1053–1057PubMedCrossRef

22.

Tse GM, Ma TK, Chan KF, Law BK, Chen MH, Li KH, Chan EC, Mak MK (2001) Increased microvessel density in malignant and borderline mammary phyllodes tumours. Histopathology 38:567–570PubMedCrossRef

23.

Kuijper A, de Vos RA, Lagendijk JH, van der Wall E, van Diest PJ (2005) Progressive deregulation of the cell cycle with higher tumor grade in the stroma of breast phyllodes tumors. Am J Clin Pathol 123:690–698PubMedCrossRef

24.

Sawyer EJ, Hanby AM, Rowan AJ, Gillett CE, Thomas RE, Poulsom R, Lakhani SR, Ellis IO, Ellis P, Tomlinson IP (2002) The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours. J Pathol 196:437–444PubMedCrossRef

25.

Sawyer EJ, Hanby AM, Poulsom R, Jeffery R, Gillett CE, Ellis IO, Ellis P, Tomlinson IP (2003) Beta-catenin abnormalities and associated insulin-like growth factor expression are important in phyllodes tumours and fibroadenomas of the breast. J Pathol 200:627–632PubMedCrossRef

26.

Lae M, Vincent-Salomon A, Savignoni A, Huon I, Freneaux P, Sigal-Zafrani B, Aurias A, Sastre-Garau X, Couturier J (2007) Phyllodes tumors of the breast segregate in two groups according to genetic criteria. Mod Pathol 20:435–444PubMedCrossRef

27.

Lv S, Niu Y, Wei L, Liu Q, Wang X, Chen Y (2008) Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study. Breast Cancer Res Treat 112:411–418PubMedCrossRef

28.

Agelopoulos K, Kersting C, Korsching E, Schimdt H, Kuijper A, August C, Wulfing P, Tio J, Boecker W, van Diest PJ, Brandt B, Buerger H (2007) EGFR amplification specific gene expression in phyllodes tumours of the breast. Cell Oncol 29:443–451PubMed

29.

Jones AM, Mitter R, Poulsom R, Gillett C, Hanby AM, Pyhllodes Tumour Consortium, Tomlinson IPM, Sawyer EJ (2008) mRNA expression profiling of phyllodes tumours of the breast: identification of genes important in the development of borderline and malignant phyllodes tumours. J Pathol 216:408–417

30.

Yang XJ, Tan MH, Kim HL et al (2005) A molecular classification of papillary renal cell carcinoma. Cancer Res 65:5628–5637PubMedCrossRef

31.

Ihaka R, Gentleman R (1996) R: a language for data analysis and graphics. J Comput Graph Stat 5:299–314CrossRef

32.

Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang J, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80PubMedCrossRef

33.

Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, Bunney WE, Myers RM, Speed TP, Akil H, Watson SJ, Meng F (2005) Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucl Acids Res 33:e175PubMedCrossRef

34.

Dykema KJ, Furge KA (2004) Diminished transcription of chromosome arm 4q is inversely related to local spreading of hepatocellular carcinoma. Genes Chromosom Cancer 41(4):390–394PubMedCrossRef

35.

Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Statistical applications in genetics and molecular biology [electronic resource] 3004:3:Article 3

36.

Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57:289–300

37.

Zeltser L, Desplan C, Heintz N (1996) Hoxb-13: a new Hox gene in a distant region of the HOXB cluster maintains colinearity. Development 122:2475–2484PubMed

38.

Ma X-J, Wang Z, Ryan PD, Isakoff SJ, Barmettler A, Fuller A, Muir B, Mohapatra G, Salunga R, Tuggle JT, Tran Y, Tran D, Tassin A, Amon P, Wang W, Wang W, Enright E, Stecker K, Estepa-Sabal E, Smith B, Younger J, Balis U, Michaelson J, Bhan A, Habin K, Baer TM, Brugge J, Haber DA, Erlander MG, Sgroi DC (2004) A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell 5:607–616PubMedCrossRef

39.

Cantile M, Pettinato G, Procino A, Feliciello I, Cindolo L, Cillo C (2003) In vivo expression of the whole HOX gene network in human breast cancer. Eur J Cancer 39:257–264PubMedCrossRef

40.

Yamashita T, Tazawa S, Yawei Z, Katayama H, Kato Y, Nishiwaki K, Yokohama Y, Ishikawa M (2006) Suppression of invasive characteristics by antisense introduction of overexpression HOX genes in ovarian cancer cells. Int J Oncol 28:931–938PubMed

41.

Miao J, Wang Z, Porvencher H, Muir B, Dahiya S, Carney E, Leong C-O, Sgroi D, Orsulic S (2007) HOXB13 promotes ovarian cancer progression. PNAS 104(43):17093–17098PubMedCrossRef

42.

Jung C, Kim R-S, Zhang H, Lee S-J, Sheng H, Loehrer PJ, Gardner TA, Jeng M-H, Kao C (2005) HOXB13 is downregulated in colorectal cancer to confer TCF4-mediated transactivation. Br J Cancer 92:2233–2239PubMedCrossRef

43.

Jung C, Kim RS, Zhang H, Lee SJ, Jeng MH (2004) HOXB13 induces growth suppression of prostate cancer cells as a repressor of hormone-activated androgen receptor signalling. Cancer Res 64:9185–9192PubMedCrossRef

44.

Jung C, Kim RS, Lee SJ, Wang C, Jeng MH (2004) HOXB13 homeodomain protein suppresses the growth of prostate cancer cells by the negative regulation of T-cell factor 4. Cancer Res 64:3046–3051PubMedCrossRef

45.

Abate-Shen C (2002) Dergulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer 2:777–785PubMedCrossRef

46.

Tse GMK, Niu Y, Shi H-J (2009) Phyllodes tumor of the breast: an update. Breast Cancer (2009 May 12, Epub)

Titel: Molecular classification of breast phyllodes tumors: validation of the histologic grading scheme and insights into malignant progression
verfasst von: Mei Kim Ang
Aik Seng Ooi
Aye Aye Thike
Patrick Tan
Zhongfa Zhang
Karl Dykema
Kyle Furge
Bin Tean Teh
Puay Hoon Tan
Publikationsdatum: 01.09.2011
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2011
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-010-1204-5

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