ORIGINAL ARTICLE
Is it ductal carcinoma in situ with microinvasion or “Ductogenesis”? The role of myoepithelial cell markers
This article has the following note(s):
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NOTIFICATION: Is it Ductal Carcinoma in Situ with Microinvasion or “Ductogenesis”? The Role of Myoepithelial Cell Markers
- Volume 2025Issue 1The Breast Journal
- First Published online: January 13, 2025
Shahla Masood MD,
Corresponding Author
Shahla Masood MD
Department of Pathology, University of Florida College of Medicine – Jax, Jacksonville, FL, USA
Correspondence
Shahla Masood, Department of Pathology, University of Florida College of Medicine – Jax, 655 W. 8th Street, Jacksonville, FL 32209, USA.
Email: [email protected]
Search for more papers by this authorShahla Masood MD,
Corresponding Author
Shahla Masood MD
Department of Pathology, University of Florida College of Medicine – Jax, Jacksonville, FL, USA
Correspondence
Shahla Masood, Department of Pathology, University of Florida College of Medicine – Jax, 655 W. 8th Street, Jacksonville, FL 32209, USA.
Email: [email protected]
Search for more papers by this authorAbstract
Mammary myoepithelial cells have been under-recognized for many years since they were considered less important in breast cancer tumorigenesis compared to luminal epithelial cells. However, in recent years with advances in genomics, cell biology, and research in breast cancer microenvironment, more emphasis has been placed on better understanding of the role that myoepithelial cells play in breast cancer progression. As the result, it has been recognized that the presence or absence of myoepithelial cells play a critical role in the assessment of tumor invasion in diagnostic breast pathology. In addition, advances in screening mammography and breast imaging has resulted in increased detection of ductal carcinoma in situ and consequently more diagnosis of ductal carcinoma in situ with microinvasion. In the present review, we discuss the characteristics of myoepithelial cells, their genomic markers and their role in the accurate diagnosis of ductal carcinoma in situ with microinvasion. We also share our experience with reporting of various morphologic features of ductal carcinoma in situ that may mimic microinvasion and introduce the term of ductogenesis.
REFERENCES
- 1Barsky SH, Karlin NJ. Mechanisms of disease: breast tumor pathogenesis and the role of the myoepithelial cell. Nat Clin Pract Oncol. 2006; 3: 138-151.
- 2Deugnier MA, Teulier J, Faraldo MM, et al. The importance of being a myoepithelial cell. Breast Cancer Res. 2002; 4: 224-230.
- 3Lakhani SR, O’Hare MJ. The mammary myoepithelial cell - Cinderella or ugly sister? Breast Cancer Res. 2001; 3: 1-4.
- 4Polyak K, Hu M. Do myoepithelial cells hold the key for breast tumor progression? J Mammary Gland Biol Neoplasia. 2005; 10: 231-247.
- 5Sternlicht MD, Barsky SH. The myoepithelial defense: a host defense against cancer. Med Hypotheses. 1997; 48: 37-46.
- 6Allinen M, Beroukhim R, Cali L, et al. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell. 2004; 6: 17-32.
- 7Barsky SH. Myoepithelial mRNA expression profiling reveals a common tumor – suppressor phenotype. Exp Mol Pathol. 2003; 74: 113-122.
- 8Sternlicht MD, Kedeshian P, Shao Z, et al. The human myoepithelial cell is a natural tumor suppressor. Clin Cancer Res. 1997; 3: 1949-1958.
- 9Schnitt SJ. The transition from ductal carcinoma in situ to invasive breast cancer: the other side of the coin. Breast Cancer Res. 2009; 11: 1010.
- 10Hu M, Yao J, Cai L, et al. Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet. 2005; 37: 899-905.
- 11Hilson JB, Schnitt SJ, Collins LC. Phenotypic alterations in myoepithelial cells associated with benign sclerosing lesions of the breast. Am J Surg Pathol. 2010; 34: 896-900.
- 12Werling RW, Hwang H, Yaziji H, et al. Immunohistochemcial distinction of invasive from noninvasive breast lesions. Am J Surg Pathol. 2003; 27: 82-90.
- 13Chivukula M, Domfeh A, Carter G, et al. Characterization of high-grade ductal carcinoma in situ with and without regressive changes: diagnostic and biologic implications. Appl Immunohistochem Mol Morphol. 2009; 17: 495-499.
- 14Hilson JB, Schnitt SJ, Collins LC. Phenotypic alterations in ductal carcinoma in situ-associated myoepithelial cells: biologic and diagnostic implications. Am J Surg Pathol. 2009; 33: 227-232.
- 15Egan MJ, Newman J, Crocker J, et al. Immunohistochemcial localization of S100 protein in benign and malignant conditions of the breast. Arch Pathol Lab Med. 1987; 111: 28-31.
- 16Kahn HJ, Marks A, Thom H, et al. Role of antibody to S100 protein in diagnostic pathology. Am J Clin Pathol. 1983; 79: 341-347.
- 17Nayar R, Breland C, Bedrossian U, et al. Immunoreactivity of ductal cells with putative myoepithelial markers: a potential pitfall in breast carcinoma. Ann Diagn Pathol. 1999; 3: 165-173.
- 18Damiani S, Ludvikova M, Tomasic G, et al. Myoepithelial cells and basal lamina in poorly differentiated in situ duct carcinoma of the breast: an immunocytochemical study. Virchows Arch. 1999; 434: 227-234.
- 19Tsubura A, Shikata N, Unui T, et al. Immunohistochemcial localization of myoepithelial cells and basement memberane in normal, benign and malignant human breast lesions. Virchows Arch A Pathol Anat Histopathol. 1988; 413: 133-139.
- 20Guelstein VI, Tchypysheva TA, Ermilova VD, et al. Myoepithelial and basement membrane antigens in benign and malignant human breast tumors. Int J Cancer. 1993; 53: 269-277.
- 21Gusterson BA, Warburton MJ, Mitchell D, et al. Distribution of myoepithelial cells and basement membrane proteins in the normal breast and in benign and malignant breast disease. Cancer Res. 1982; 42: 4763-4770.
- 22Gottlieb C, Raju U, Greenwald KA. Myoepithelial cells in the differential diagnosis of complex benign and malignant breast lesions: an immunohistochemcial study. Mod Pathol. 1990; 3: 135-140.
- 23Jarasch ED, Nagle RB, Kaufmann M, et al. Differential diagnosis of benign epithelialproliferations and carcinomas of the breast using antibodies to cytokeratins. Hum Pathol. 1988; 19: 276-289.
- 24Nagle RB, Bocker W, Davis J, et al. Characterization of breast carcinomas by two monoclonal antibodies distinguishing myoepithelial from luminal epithelial cells. J Histochem Cytochem. 1986; 34: 869-881.
- 25Gugliotta P, Sapino A, Macri L, et al. Specific demonstration of myoepithelial cells by anti-alpha smooth muscle actin antibody. J Histochem Cytochem. 1988; 36: 659-663.
- 26Mukai K, Schollmeyer JV, Rosai J. Immunohistochemical Localization of actin: applications in surgical pathology. Am J Surg Pathol. 1981; 5: 91-97.
- 27Papotti M, Eusebi V, Gugliotta P, et al. Immunohistochemical analysis of benign and malignant papillary lesions of the breast. Am J Surg Pathol. 1983; 7: 451-461.
- 28Skalli O, Ropraz P, Trzeciak A, et al. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986; 103: 2787-2796.
- 29Wang NP, Wan BC, Skelly M, et al. Antibodies to novel myoepithelium-associated proteins distinguish benign lesions and in situ carcinoma from invasive carcinoma of the breast. Appl Immuno-histochem. 1997; 5: 141-151.
- 30Gudjonsson T, Adriance MC, Sternlicht MD, et al. Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia. J. Mammary Gland Biol Neoplasia. 2005; 10: 261-272.
- 31Barsky SH, Karlin NJ. Myoepithelial cells: autocrine and paracrine suppressors of breast cancer progression. J Mammary Gland Biol Neoplasia. 2005; 10: 249-260.
- 32Pang JB, Savas P, Fellowes AP, et al. Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer. Mod Pathol. 2007; 30: 952-963.
- 33Mardekian SK, Bombonati A, Palazzo JP. DuDuctal carcinoma in situ of the breast: the importance of morphologic and molecular interactions. Hum Pathol. 2016; 49: 114-123.
- 34Man YG, Tai L, Barner R, et al. Cell clusters overlying focally disrupted mammary myoepithelial cell layers and adjacent cells within the same duct display different immunohistochemical and genetic features: implications for tumor progression and invasion. Breast Cancer Res. 2003; 5: R231-R241.
- 35Ma XJ, Dahiya S, Richardson E, et al. Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res. 2009; 11: R7.
- 36Gudjonsson T, Ronnov-Jessen L, Villadsen R, et al. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci. 2002; 115: 39-50.
- 37Dey P. Epigenetic changes in tumor microenvironment. Ind J Cancer. 2011; 48: 507-512.
- 38Man YG, Sang Q. The significance of facal myoepithelial cell layer disruptions in human breast tumor invasion: a paradigm shift from the ‘protease-centered’ hypothesis. Exp Cell Res. 2004; 301: 103-118.
- 39Rohilla M, Bal A, Singh G, et al. Pheotypic and functional characterization of ductal carcinoma in situ associated myoepithelial cells. Clin. Breast Cancer. 2015; 15: 335-342.
- 40Abdelkarim M, Vintonenko N, Starzec A, et al. Invading basement membrane matrix is sufficient for MDA-MB-231 breast cancer cells to develop a stable in vivo metastatic phenotype. PLoS ONE. 2001; 6:e23334.
- 41Hu M, Yao J, Carroll DK, et al. Regulation of in situ to invasive breast carcinoma transition. Cancer Cell. 2008; 13: 394-406.
- 42Adriance MC, Inman JL, Petersen OW, et al. Myoepithelial cells: good fences make good neighbors. Breast Cancer Res. 2005; 7: 190-197.
- 43Wen YH, Weigelt B, Reis-Filho JS. Microglandular adenosis: a non-obligate precursor of triple-negative breast cancer? Histol Histopathol. 2013; 18: 1099-1108.
- 44Shui RH, Cheng YF, Yang WT. Invasive carcinoma arising in breast microglandular adenosis: a clinicopathologic study of three cases and review of the literature. Zhonghua Bing Li Xue Za Zhi. 2011; 40: 471-474.
- 45Yamaguchi R, Maeshiro K, Ellis IO, et al. Infiltrative epitheliosis of the breast. J Clin Pathol. 2012; 65: 766-768.
- 46Eberle CA, Piscuoglio S, Rakha EA, et al. Infiltrating epitheliosis of the breast: characterization of histologic features, immunophenotype and genomic profile. Histopathology. 2016; 16: 1030-1039.
- 47Cserni G. Lack of myoepithelium in apocrine glands of the breast does not necessarily imply malignancy. Histopathology. 2008; 52: 253-255.
- 48Cserni G. Benign apocrine papillary lesions of the breast lacking or virtually lacking myoepithelial cells – potential pitfalls in diagnosing malignancy. APMIS. 2012; 120: 249-252.
- 49Seal M, Wilson C, Naus GJ, et al. Encapsulated apocrine papillary carcinoma of the breast – a tumour of uncertain malignant potential: report of five cases. Virchows Arch. 2009; 455: 477-483.
- 50Tan BY, Thike AA, Ellis IO, et al. Cliniopathologic characteristics of solid papillary carcinoma of the breast. Am J Surg Pathol. 2016; 40: 1334-1342.
- 51Sanders M, Lester S. Paget disease of the breast with invasion from nipple skin into the dermis. Arch Pathol Lab Med. 2013; 137: 307.
- 52Tan PH, Schnitt SJ, van de Vijver MJ, Ellis IO, Lakhani SR. Papillary and neuroendocrine breast lesions: the WHO stance. Histopathology. 2015; 66: 761-770.
- 53Nassar H, Qureshi H, Adsay NV, et al. Clinicopathologic analysis of solid papillary carcinoma of the breast and associated invasive carcinomas. Am J Surg Pathol. 2006; 30: 501-507.
- 54Lester S. Robbins and Cotran Pathologic Basis of Disease, 8th edn. Philadelphia, PA: Saunders Elsevier; 2010.
10.1016/B978-1-4377-0792-2.50028-6 Google Scholar
- 55Highland KE, Finley JL, Neill JS, et al. Collagenous spherulosis. Report of a case with diagnosis by fine needle aspiration biopsy with immunocytochemical and ultrastructual observations. Acta Cytol. 1993; 37: 3-9.
- 56Lagios MD, Westdahl P, Margolin FR, et al. Duct carcinoma in situ: relationship of extent of noninvasive disease to the frequency of occult invasion, multicentricity, lyumph node metastases, and short term treatment failures. Cancer. 1982; 50: 1309-1314.
10.1002/1097-0142(19821001)50:7<1309::AID-CNCR2820500716>3.0.CO;2-# CAS PubMed Web of Science® Google Scholar
- 57Silverstein JM, Waisman JR, Gamagami P, et al. Intraductal carcinoma of the breast (208 cases): clinical factors influencing treatment choice. Cancer. 1990; 66: 102-108.
10.1002/1097-0142(19900701)66:1<102::AID-CNCR2820660119>3.0.CO;2-5 CAS PubMed Web of Science® Google Scholar
- 58 Royal College of Pathologists Working Group. Pathology reporting in breast cancer screening. J Clin Pathol. 1991; 44: 710-725.
- 59Rosner D, Lane WW, Penetrante R. Ductal carcinoma in situ with microinvasion: a curable entity using surgery alone without need for adjuvant therapy. Cancer. 1991; 67: 1498-1503.
10.1002/1097-0142(19910315)67:6<1498::AID-CNCR2820670606>3.0.CO;2-I CAS PubMed Web of Science® Google Scholar
- 60Pinder SE, Ellis IO, Schnitt S, et al. Microinvasive carcinoma. In: SR Lakhani, IO Ellis, SJ Schnitt, P Tan, MJ Vijvair, editors. WHO classification of tumours of the breast. Lyon: IARC Press; 2012: 96-97.
- 61Bianchi S, Vezzosi V. Microinvasive carcinoma of the breast. Pathol Oncol Res. 2008; 14: 105-111.
- 62Giuliano AE, Connolly JL, Edge SB, et al. Breast cancer: major changes in the American Joint Committee on Cancer. Eight edition cancer staging manual. CA Cancer J Clin. 2017; 62: 290-303.
- 63Vieira CC, Mercado CL, Cangiarella JF Jr, et al. Microinvasive ductal carcinoma in situ: clinical presentation, imaging features, pathologic findings and outcome. Eur J Radiol. 2010; 73: 102-107.
- 64Kim M, Kim HJ, Chung YR, et al. Microinvasive carcinoma versus ductal carcinoma in situ: a comparison of clinicopathological features and clinical outcomes. J Breast Cancer. 2018; 21: 197-205.
- 65Wang L, Zhang W, Lyu S, et al. Clinicopathologic characteristics and molecular subtypes of microinvasive carcinoma of the breast. Tumour Biol. 2015; 36: 2241-2248.
- 66Orzalesi L, Casella D, Criscenti V, et al. Microinvasive breast cancer pathological parameters, cancer sub-types distribution, and correlation with axillary lymph nodes invasion. Results of a large single institution series. Breast Cancer. 2016; 23: 640-648.
- 67Lari SA, Kuerer HM. Biological markers in DCIS and risk of breast recurrence: a systematic review. J Cancer. 2011; 2: 232-261.
- 68Margalit DN, Sreedhara M, Chen YH, et al. Microinvasive breast cancer: ER, PR, and HER-2/neu status and clinical outcomes after breast conserving therapy or mastectomy. Ann Surg Oncol. 2013; 20: 811-818.
- 69Gradishar WJ, Anderson BO, Balassanian R, et al. Breast Cancer Version 2.2015. J Natl Compr Cancer Netw. 2015; 13: 448-475.
- 70Zavotsky J, Hansen N, Brennan MB, et al. Lymph Node metastasis from ductal carcinoma in situ with microinvasion. Cancer. 1999; 85: 2439-2443.
10.1002/(SICI)1097-0142(19990601)85:11<2439::AID-CNCR19>3.0.CO;2-J CAS PubMed Web of Science® Google Scholar
- 71Sopik V, Sun P, Narod ST. Impact of micoinvasion on breast cancer mortality in women with ductal carcinoma in situ. Breast Cancer Res Treat. 2018; 167: 787-795.
- 72Koscielyn S, Tubiana M, Le MG, et al. Breast cancer: relationship between the size of the primary tumor and the probability of metastatic dissemination. Br J Cancer. 1984; 49: 709-715.
- 73Tubiana M, Koscielny S. The rationale for early diagnosis of cancer-the example of breast cancer. Acta Oncol. 1999; 38: 295-303.
- 74Ponten J. Natural history of breast cancer. Acta Oncol. 1990; 29: 325-329.
- 75Ellis IO, Lee AH, Elston CW, et al. Microinvasive carcinoma of the breast: diagnostic criteria and clinical relevance. Histopathology. 1999; 35: 470-472.
- 76Schnitt SJ. Microinvasive carcinoma of the breast: a diagnosis in search of a definition. Adv Anat Pathol. 1998; 5: 367-372.
- 77Yaziji H, Gown AM, Sneige N. Gown Am, Sneige N. Detection of stromal invasion in breast cancer: the myoepithelial markers. Adv Anat Pathol. 2000; 7: 100-109.
- 78Schnitt SJ, Collins LC. Biopsy Interpretation Series: Biopsy Interpretation of the Breast. Philadelphia, PA: Lipincott Williams & Wilkins. 2009: 236-248.
