Ductal carcinoma in situ on stereotactic biopsy of suspicious breast microcalcifications: Expression of SPARC (Secreted Protein, Acidic and Rich in Cysteine) can predict postoperative invasion
Corresponding Author
Bartlomiej Szynglarewicz MD
Breast Unit, Department of Surgical Oncology, Lower Silesia Oncology Center, Wroclaw, Poland
Correspondence to: Dr. Bartlomiej Szynglarewicz, MD, Breast Unit, Department of Surgical Oncology, Lower Silesia Oncology Centre—Regional Comprehensive Cancer Center, L.Hirszelda 12, 53-431 Wroclaw, Poland. Fax: +48713689219. E-mail: [email protected]
Search for more papers by this authorPiotr Kasprzak MD
Department of Breast Imaging, Lower Silesia Oncology Center, Wroclaw, Poland
Search for more papers by this authorPiotr Donizy MD
Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland
Search for more papers by this authorPrzemyslaw Biecek MSc
Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, Warsaw, Poland
Search for more papers by this authorAgnieszka Halon MD
Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland
Search for more papers by this authorRafal Matkowski MD
Breast Unit, Department of Surgical Oncology, Lower Silesia Oncology Center, Wroclaw, Poland
Department of Oncology, Wroclaw Medical University, Wroclaw, Poland
Search for more papers by this authorCorresponding Author
Bartlomiej Szynglarewicz MD
Breast Unit, Department of Surgical Oncology, Lower Silesia Oncology Center, Wroclaw, Poland
Correspondence to: Dr. Bartlomiej Szynglarewicz, MD, Breast Unit, Department of Surgical Oncology, Lower Silesia Oncology Centre—Regional Comprehensive Cancer Center, L.Hirszelda 12, 53-431 Wroclaw, Poland. Fax: +48713689219. E-mail: [email protected]
Search for more papers by this authorPiotr Kasprzak MD
Department of Breast Imaging, Lower Silesia Oncology Center, Wroclaw, Poland
Search for more papers by this authorPiotr Donizy MD
Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland
Search for more papers by this authorPrzemyslaw Biecek MSc
Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, Warsaw, Poland
Search for more papers by this authorAgnieszka Halon MD
Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland
Search for more papers by this authorRafal Matkowski MD
Breast Unit, Department of Surgical Oncology, Lower Silesia Oncology Center, Wroclaw, Poland
Department of Oncology, Wroclaw Medical University, Wroclaw, Poland
Search for more papers by this authorAbstract
Background and Objectives
Secreted protein, acidic and rich in cysteine (SPARC) is able to play an important role in cancer invasion due to de-adhesive properties and impact on stromal remodeling. The aim of study was to investigate SPARC expression in preoperatively diagnosed breast DCIS and to assess its predictive value for the final invasion.
Methods
A total of 209 patients with DCIS found on stereotactic vacuum-assisted biopsy of suspicious microcalcifications were studied prospectively.
Results
SPARC staining was positive in luminal epithelial cells, stromal fibroblasts, and myoepithelial cells in 38%, 62%, and 61% of tumors, respectively. Neither patient age nor pattern of microcalcifications were related to SPARC expression. High nuclear grade and comedonecrosis were associated with strong immunoreactivity of SPARC in stromal fibroblasts and myoepithelial cells while not in luminal epithelial cells. Rate of postoperative invasion was significantly increased in DCIS with strong SPARC staining with regard to all investigated cells. None of standard parameters significantly influenced the upgrading risk. In multivariate analysis most significant and independent predictive factors were strong SPARC expression in luminal epithelial cells, and stromal fibroblasts.
Conclusions
SPARC can be a new biomarker helpful to identify more aggressive DCIS and for prediction of invasive disease on final pathology. J. Surg. Oncol. 2016;114:548–556. © 2016 Wiley Periodicals, Inc.
REFERENCES
- 1 Hohenester E, Maurer P, Hohenadl C, et al.: Structure of a novel etracellular Ca(2+)-binding module in BM-40. Nat Struct Biol 1996; 3: 67–73.
- 2 Bornstein P: Matricellular proteins: An overview. J Cell Commun Signal 2009; 3: 163–165.
- 3
Motamed K:
Sage EH: SPARC inhibits endothelial cell adhesion but not proliferation throuh a tyrosine phosphorylation-dependent pathway.
J Cell Biochem
1998;
70: 543–552.
10.1002/(SICI)1097-4644(19980915)70:4<543::AID-JCB10>3.0.CO;2-I CAS PubMed Web of Science® Google Scholar
- 4 Murphy-Ullrich JE, Lane TF, Pallera MA, et al.: SPARC mediates focal adhesion disassembly in endothelial cells through a follistatin-like region and the Ca2+-binding EF-hand. J Cell Biochem 1995; 57: 341–350.
- 5 Clark CJ, Sage EH: A prototypic matricellular protein in the tumor microenvironment—where there's SPARC, there's fire. J Cell Biochem 2008; 104: 721–732.
- 6 Sage EH, Bornstein P: Extracellular proteins that modulate cell-matrix interactions. SPARC, tenascin, and thrombospondin. J Biol Chem 1991; 266: 14831–14834.
- 7 Chen CC, Lau LF: Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol 2009; 41: 771–783.
- 8 Dvorak HF: Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986; 315: 1650–1659.
- 9 Witz IP, Levy-Nissenbaum O: The tumor microenvironment in the post-PAGET era. Cancer Lett 2006; 242: 1–10.
- 10 Potter JD: Morphogens, morphostats, microarchitecture, and malignancy. Nat Rev Cancer 2007; 7: 464–474.
- 11 Li H, Fan X, Houghton J: Tumor microenvironment: The role of the tumor stroma in cancer. J Cell Biochem 2007; 101: 805–815.
- 12 Framson PE, Sage EH: SPARC and tumor growth: Where the seed meets the soil? J Cell Biochem 2004; 92: 679–690.
- 13 Porter PL, Sage EH, Lane TF, et al.: Distribution of SPARC in normal and neoplastic human tissue. J Histochem Cytochem 1995; 43: 791–800.
- 14 Nagaraju GP, Dontula R, El-Rayes BF, et al.: Molecular mechanisms underlying the divergent roles of SPARC in human carcinogenesis. Carcinogenesis 2014; 35: 967–973.
- 15 Ernster VL, Ballard-Barbash R, Barlow WE, et al.: Detection of ductal carcinoma in situ in women undergoing screening mammography. J Natl Cancer Inst 2002; 94: 1546–1554.
- 16 Gajdos C, Tartter PI, Bleiweiss IJ, et al.: Mammographic appearance of nonpalpable breast cancer reflects pathologic characteristics. Ann Surg 2002; 235: 246–251.
- 17 de Roos MA, van der Vegt B, de Vries J, et al.: Pathological and biological differences between screen-detected and interval ductal carcinoma in situ of the breast. Ann Surg Oncol 2007; 14: 2097–2104.
- 18 Silvertein MJ, Recht A, Lagios MD, et al.: Special report: Consensus conference III. Image-detected breast cancer: State-of-the-art diagnosis and treatment. J Am Coll Surg 2009; 209: 504–520.
- 19 Knudsenm ES, Ertel A, Davicioni E, et al.: Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia. Breast Cancer Res Treat 2012; 133: 1009–1024.
- 20 Lester SC, Bose S, Chen YY, et al.: Protocol for the examination of specimens from patients with ductal carcinoma in situ of the breast. Arch Pathol Lab Med 2009; 133: 15–25.
- 21
Schwartz GF,
Lagios MD,
Carter D, et al.:
Consensus conference on the classification of ductal carcinoma in situ.
Cancer
1997;
80: 1798–1802.
10.1002/(SICI)1097-0142(19971101)80:9<1798::AID-CNCR15>3.0.CO;2-0 PubMed Web of Science® Google Scholar
- 22 Tabar L, Tot T, Dean PB: Breast Cancer: The Art and Science of Early Detection With Mammography, 1st edition. Stuttgart, New York: Thieme; 2005.
- 23 Szynglarewicz B, Kasprzak P, Biecek P, et al: Screen-detected carcinoma in situ found on stereotactic vacuum-assisted biopsy of suspicious microcalcifications without mass: Radiological–histological correlation. Radiol Oncol 2016; 50: 145–152.
- 24 Lee SK, Yang JH, Woo SY, et al.: Nomogram for predicting invasion in patients with preoperative diagnosis of ductal carcinoma in situ of the breast. Br J Surg 2013; 100: 1756–1763.
- 25 Schulz S, Sinn P, Golatta M, et al.: Prediction of underestimated invasiveness in patients with ductal carcinoma in situ of the breast on percutaneous biopsy as rationale for recommending concurrent sentinel lymph node biopsy. Breast 2013; 22: 537–542.
- 26 Park HS, Park S, Cho J, et al.: Risk predictors of underestimation and the need for sentinel node biopsy in patients diagnosed with ductal carcinoma in situ by preoperative needle biopsy. J Surg Oncol 2013; 107: 388–392.
- 27 Osako T, Iwase T, Ushijima M, et al.: Incidence and prediction of invasive disease and nodal metastasis in preoperatively diagnosed ductal carcinoma in situ. Cancer Sci 2014; 105: 576–582.
- 28 Kim J, Han W, Lee JW, et al.: Factors associated with upstaging from ductal carcinoma in situ following core needle biopsy to invasive cancer in subsequent surgical excision. Breast 2012; 21: 641–645.
- 29 Han JS, Molberg KH, Sarode V: Predictors of invasion and axillary lymph node metastasis in patients with a core biopsy diagnosis of ductal carcinoma in situ: An analysis of 255 cases. Breast J 2011; 17: 223–229.
- 30 Szynglarewicz B, Kasprzak P, Halon A, et al.: Preoperatively diagnosed ductal cancers in situ of the breast presenting as even small masses are of high risk for the invasive cancer foci in postoperative specimen. World J Surg Oncol 2015; 13: 218.
- 31 Iacobuzio-Donahue CA, Argani P, Hempen PM, et al.: The desmoplastic response to infiltrating breast carcinoma: Gene expression at the site of primary invasion and implications for comparisons between tumor types. Cancer Res 2002; 62: 5351–5357.
- 32 Briggs J, Chamboredon S, Castellazzi M, et al.: Transcriptional upregulation of SPARC, in response to c-Jun overexpression, contributes to increased motility, and invasion of MCF7 breast cancer cells. Oncogene 2002; 21: 7077–7091.
- 33 Gilles C, Bassuk JA, Pulyeva H, et al.: SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res 1998; 58: 5529–5536.
- 34 Dhanesuan N, Sharp JA, Blick T, et al.: Doxycycline-inducible expression of SPARC/osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition. Breast Cancer Res Treat 2002; 75: 73–85.
- 35 Koblinski JE, Kaplan-Singer BR, VanOsdol SJ, et al.: Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis. Cancer Res 2005; 65: 7370–7377.
- 36 Watkins G, Douglas-Jones A, Bryce R, et al.: Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes. Prostaglandins Leucot Essent Fatty Acids 2005; 72: 267–272.
- 37 Gerson KD, Shearstone JR, Maddula VS, et al.: Integrin β4 regulates SPARC protein to promote invasion. J Biol Chem 2012; 287: 9835–9844.
- 38 Barth PJ, Moll R, Ramaswamy A: Stroma remodeling and SPARC (secreted protein acid rich in cysteine) expression in invasive ductal carcinomas of the breast. Virchows Arch 2005; 446: 532–536.
- 39 Choi Y, Lee HJ, Jang MH, et al.: Epithelial-mesenchymal transition increases during progression of in situ to invasive basal-like breast cancer. Hum Pathol 2013; 44: 2581–2589.
- 40 Jang MH, Kim HJ, Kim EJ, et al.: Expression of epithelial-mesenchymal transition-related markers in triple-negative breast cancer: ZEB1 as a potential biomarker for poor clinical outcome. Hum Pathol 2015; 46: 1267–1274.
- 41 Hsiao YH, Lien HC, Hwa HL, et al.: SPARC (Osteonectin) i breast tumors of different histologic types and its role in the outcome of invasive ductal carcinoma. Breast J 2010; 16: 305–308.
- 42 Witkiewicz AK, Freydin B, Chervoneva I, et al.: Stromal CD10 and SPARC expression in ductal carcinoma in situ (DCIS) patients predicts disease recurrence. Cancer Biol Ther 2010; 10: 391–396.
- 43 Ma XJ, Dahiya S, Richardson E, et al.: Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res 2009; 11: R7.
- 44 Allinen M, Beroukhim R, Cai L, et al.: Molecular characterisation of the tumor microenvironment in breast cancer. Cancer Cell 2004; 6: 17–32.
- 45 Wellings SR, Jensen HM: On the origin and progression of ductal carcinoma in the human breast. J Natl Cancer Inst 1973; 50: 1111–1118.
- 46 Carter CL, Corle DK, Micozzi MS, et al.: A prospective study of the development of breast cancer in 16,692 women with benign breast disease. Am J Epidemiol 1988; 128: 467–477.
- 47 Buerger H, Mommers EC, Littmann R, et al.: Ductal invasive G2 and G3 carcinomas of the breast are the end stages of at least two different lines of genetic evolution. J Pathol 2001; 194: 165–170.
- 48 Roylance R, Gorman P, Hanby A, et al.: Allelic imbalance analysis of chromosome 16q shows that grade I and grade III invasive ductal breast cancers follow different genetic pathways. J Pathol 2002; 196: 32–36.
- 49 Hwang ES, DeVries S, Chew KL, et al.: Patterns of chromosomal alterations in breast dustl carcinoma in situ. Clin Cancer Res 2004; 10: 5160–5167.
- 50 Torres L, Ribeiro FR, Pandis N, et al.: Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases. Breast Cancer Res Treat 2007; 102: 143–155.
- 51 Allred DC, Wu Y, Mao S, et al.: Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution. Clin Cancer Res 2008; 14: 370–378.
- 52 Cunha PO, Ornstein M, Jones JL: Progression of ductal carcinoma in situ from the pathological perspective. Breast Care (Basel) 2010; 5: 233–239.
- 53 Klein CA: Parallel progression of primary tumours and metastases. Nat Rev Cancer 2009; 9: 302–312.
- 54 Husemann Y, Geigl JB, Schubert F, et al.: Systemic spread is an early step in breast cancer. Cancer Cell 2008; 13: 58–68.
- 55 Inoue K, Fry EA: Novel molecular markers for breast cancer. Biomark Cancer 2016; 8: 25–42.
- 56 Doebar SC, de Monye C, Stoop H, et al.: Ductal carcinoma in situ diagnosed by breast needle biopsy Predictors of invasion in the excision specimen. Breast 2016; 27: 15–21.
