Top

Published in:

Open Access 01-12-2010 | Research

Diagnostic utility of snail in metaplastic breast carcinoma

Authors: Aziza Nassar, Nicole Sookhan, Marta Santisteban, Sandra C Bryant, Judy C Boughey, Tamar Giorgadze, Amy Degnim

Published in: Diagnostic Pathology | Issue 1/2010

Abstract

Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer characterized by coexistence of carcinomatous and sarcomatous components. Snail is a nuclear transcription factor incriminated in the transition of epithelial to mesenchymal differentiation of breast cancer. Aberrant Snail expression results in lost expression of the cell adhesion molecule E-cadherin, an event associated with changes in epithelial architecture and invasive growth. We aimed to identify the utility of Snail, and of traditional immunohistochemical markers, in accurate MBC classification and to evaluate clinicopathologic characteristics and outcome.

We retrospectively reviewed 34 MBC cases from January 1997 to September 2007. The control group contained 26 spindle cell lesions. Immunohistochemistry used Snail, p63, epidermal growth factor receptor (EGFR), OSCAR, and wide spectrum cytokeratin (WS-KER). Negative was a score less than 1%. We found that Snail and EGFR are sensitive (100%) markers with low specificity (3.8% and 19.2%) for detecting MBC. p63 and WS-KER are specific (100%), with moderate sensitivity (67.6% and 76.5%); OSCAR is sensitive (85.3%) and specific (92.3%). A combination of any 2 of the p63, OSCAR, and WS-KER markers increased sensitivity and specificity. MBCs tended to be high-grade (77%), triple negative (negative for estrogen receptor, progesterone receptor, and HER2) [27/33; 81.8%], and carcinomas with low incidence of axillary lymph node involvement (15%), and decreased disease-free [71% (95%CI: 54%, 94%) at 3 yrs.) and overall survival. A combination of p63, OSCAR and WS-KER are useful in its work-up. On the other hand, Snail is neither a diagnostic nor a prognostic marker for MBC.

Available only for authorised users

Luini A, Aguilar M, Gatti G, Fasani R, Botteri E, Brito JA, Maisonneuve P, Vento AR, Viale G: Metaplastic carcinoma of the breast, an unusual disease with worse prognosis: the experience of the European Institute of Oncology and review of the literature. Breast Cancer Res Treat. 2007, 101: 349-353. 10.1007/s10549-006-9301-1.CrossRefPubMed

Günhan-Bilgen I, Memis A, Ustun EE, Zekioglu O, Ozdemir N: Metaplastic carcinoma of the breast: clinical, mammographic, and sonographic findings with histopathologic correlation. AJR. 2002, 178: 1421-1425.CrossRefPubMed

Park JM, Han BK, Moon WK, Choe YH, Ahn SH, Gong G: Metaplastic carcinoma of the breast: mammographic and sonographic findings. J Clin Ultrasound. 2000, 28: 179-186. 10.1002/(SICI)1097-0096(200005)28:4<179::AID-JCU5>3.0.CO;2-Y.CrossRefPubMed

Lien HC, Hsiao YH, Lin YS, Yao YT, Juan HF, Kuo WH, Hung MC, Chang KJ, Hsieh FJ: Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: identification of genes potentially related to epithelial-mesenchymal transition. Oncogene. 2007, 26 (57): 7859-71. 10.1038/sj.onc.1210593.CrossRefPubMed

Knutson KL, Lu H, Stone B, Reiman JM, Behrens MD, Prosperi CM, Gad EA, Smorlesi A, Disis ML: Immunoediting of cancers may lead to epithelial to mesenchymal transition. J Immunol. 2006, 177 (3): 1526-33.CrossRefPubMed

Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brishen C, Yang J, Weinberg RA: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008, 133 (4): 704-15. 10.1016/j.cell.2008.03.027.PubMedCentralCrossRefPubMed

Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, Haluska P, Ingle JN, Hartmann LC, Manjili MH, Radisky DC, Ferrone S, Knutson KL: Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009, 69 (7): 2887-95. 10.1158/0008-5472.CAN-08-3343.PubMedCentralCrossRefPubMed

Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, Notorfrancesco KL, Cardiff RD, Chodosh LA: The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 2005, 8 (3): 197-209. 10.1016/j.ccr.2005.07.009.CrossRefPubMed

Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA: The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000, 2 (2): 76-83. 10.1038/35000025.CrossRefPubMed

10.

Zhou BP, Hung MC: Wnt, hedgehog and Snail: sister pathways that control by GSK-3beta and beta-Trcp in the regulation of metastasis. Cell Cycle. 2005, 4 (6): 772-6. 10.4161/cc.4.6.1744.CrossRefPubMed

11.

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lǿnning PE, Bǿrresen-Dale AL, Brown PO, Botstein D: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98 (19): 10869-74. 10.1073/pnas.191367098.PubMedCentralCrossRefPubMed

12.

van't Veer LJ, Paik S, Hayes DF: Gene expression profiling of breast cancer: a new tumor marker. J Clin Oncol. 2005, 23 (8): 1631-5. 10.1200/JCO.2005.12.005.CrossRefPubMed

13.

Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, Talantov D, Timmermans M, Meijer-van Gelder ME, Yu J, Jutkoe T, Berns EM, Atkins D, Foekens JA: Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005, 365 (9460): 671-9.CrossRefPubMed

14.

Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, Wade PA: MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell. 2003, 113 (2): 207-19. 10.1016/S0092-8674(03)00234-4.CrossRefPubMed

15.

Dunne B, Lee AH, Pinder SE, Bell JA, Ellis IO: An immunohistochemical study of metaplastic spindle cell carcinoma, phyllodes tumor and fibromatosis of the breast. Hum Pathol. 2003, 34: 1009-1015. 10.1053/S0046-8177(03)00414-3.CrossRefPubMed

16.

Wargotz ES, Deos PH, Norris HJ: Metaplastic carcinomas of the breast. II. Spindle cell carcinoma. Hum Pathol. 1989, 20: 732-740. 10.1016/0046-8177(89)90065-8.CrossRefPubMed

17.

Wargotz ES, Norris HJ: Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma. Hum Pathol. 1989, 20: 628-635. 10.1016/0046-8177(89)90149-4.CrossRefPubMed

18.

Wargotz ES, Norris HJ: Metaplastic carcinomas of the breast. III. Carcinosarcoma. Cancer. 1989, 64: 1490-1499. 10.1002/1097-0142(19891001)64:7<1490::AID-CNCR2820640722>3.0.CO;2-L.CrossRefPubMed

19.

Wargotz ES, Norris HJ: Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin. Cancer. 1990, 65: 272-276. 10.1002/1097-0142(19900115)65:2<272::AID-CNCR2820650215>3.0.CO;2-6.CrossRefPubMed

20.

Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, Nieto MA: Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene. 2002, 21 (20): 3241-6. 10.1038/sj.onc.1205416.CrossRefPubMed

21.

Rosen PP, Ernsberger D: Low-grade adenosquamous carcinoma. A variant of metaplastic mammary carcinoma. Am J Surg Pathol. 1987, 11: 351-358. 10.1097/00000478-198705000-00003.CrossRefPubMed

22.

Sneige N, Yaziji H, Mandavilli SR, Perez ER, Ordonez NG, Gown AM, Ayala A: Low-grade (fibromatosis-like) spindle cell carcinoma of the breast. Am J of Surg Pathol. 2001, 25: 1009-1016. 10.1097/00000478-200108000-00004.CrossRef

23.

Brogi E: Benign and malignant spindle cell lesions of the breast. Semin Diagn Pathol. 2004, 21: 57-64. 10.1053/j.semdp.2003.10.007.CrossRefPubMed

24.

Dave G, Cosmatos H, Do T, Lodin K, Varshney D: Metaplastic carcinoma of the breast: a retrospective review. Int J Radiat Oncol Biol Phys. 2006, 64: 771-775. 10.1016/j.ijrobp.2005.08.024.CrossRefPubMed

25.

Downs-Kelly E, Nayeemuddin KM, Albarracin C, Wu Y, Hunt KK, Gilcrease MZ: Matrix-producing Carcinoma of the Breast: An Aggressive Subtype of Metaplastic Carcinoma. Am J Surg Pathol. 2009, 33 (4): 534-41. 10.1097/PAS.0b013e31818ab26e.CrossRefPubMed

26.

Hennessy BT, Giordano S, Broglio K, Duan Z, Trent J, Buchholz TA, Babiera G, Hortobagyi GN, Valero V: Biphasic metaplastic sarcomatoid carcinoma of the breast. Ann Oncol. 2006, 17: 605-613. 10.1093/annonc/mdl006.CrossRefPubMed

27.

Carter MR, Hornick JL, Lester S, Fletcher CD: Spindle cell (sarcomatoid) carcinoma of the breast: a clinicopathologic and immunohistochemical analysis of 29 cases. Am J Surg Pathol. 2006, 30: 300-309.PubMed

28.

Khan HN, Wyld L, Dunne B, Lee AH, Pinder SE, Evans AJ, Robertson JF: Spindle cell carcinoma of the breast: a case series of a rare histological subtype. Eur J Surg Oncol. 2003, 29: 600-603. 10.1016/S0748-7983(03)00107-0.CrossRefPubMed

29.

Al Sayed AD, El Weshi AN, Tulbah AM, Rahal MM, Ezzat AA: Metaplastic carcinoma of the breast clinical presentation, treatment results and prognostic factors. Acta Oncol (Stockholm, Sweden). 2006, 45: 188-195. 10.1080/02841860500513235.CrossRef

30.

Chao TC, Wang CS, Chen SC, Chen MF: Metaplastic carcinomas of the breast. J Surg Oncol. 1999, 71: 220-225. 10.1002/(SICI)1096-9098(199908)71:4<220::AID-JSO3>3.0.CO;2-L.CrossRefPubMed

31.

Gibson GR, Qian D, Ku JK, Lai LL: Metaplastic breast cancer: clinical features and outcomes. Am Surg. 2005, 71: 725-730.PubMed

32.

Kurian KM, Al-Nafussi A: Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological study of 12 cases. Histopathology. 2002, 40: 58-64. 10.1046/j.1365-2559.2002.01319.x.CrossRefPubMed

33.

Gilbert JA, Goetz MP, Reynolds CA, Ingle JN, Giordano KF, Suman VJ, Blair HE, Jenkins RB, Lingle WL, Reinholz MM, Adjei AA, Ames MM: Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy. Mol Cancer Ther. 2008, 7: 944-951. 10.1158/1535-7163.MCT-07-0570.PubMedCentralCrossRefPubMed

34.

Gobbi H, Simpson JF, Jensen RA, Olson SJ, Page DL: Metaplastic spindle cell breast tumors arising within papillomas, complex sclerosing lesions, and nipple adenomas. Mod Pathol. 2003, 16: 893-901. 10.1097/01.MP.0000085027.75201.B5.CrossRefPubMed

35.

Denley H, Pinder SE, Tan PH, Sim CS, Brown R, Barker T, Gearty J, Elston CW, Ellis IO: Metaplastic carcinoma of the breast arising within complex sclerosing lesion: a report of five cases. Histopathology. 2000, 36: 203-209. 10.1046/j.1365-2559.2000.00849.x.CrossRefPubMed

36.

Tse GM, Tan PH, Lui PC, Putti TC: Spindle cell lesions of the breast--the pathologic differential diagnosis. Breast Cancer Res Treat. 2008, 109: 199-207. 10.1007/s10549-007-9652-2.CrossRefPubMed

37.

Reis-Filho JS, Milanezi F, Paredes J, Silva P, Pereira EM, Maeda SA, de Carvalho LV, Schmitt FC: Novel and Classic Myoepithelial/Stem Cell Markers in Metaplastic Carcinomas of the Breast. Appl Immunohistochem Mol Morphol. 2003, 11: 1-8. 10.1097/00022744-200303000-00001.PubMed

38.

Popnikolov NK, Ayala AG, Graves K, Gatalica Z: Benign Myoepithelial Tumors of the Breast Have Immunophenotype Characteristics Similar to Metaplastic Matrix Producing and Spindle Cell Carcinomas. Am J Clin Pathol. 2003, 120: 161-167. 10.1309/G6CTR8MDTFUW19XV.CrossRefPubMed

39.

Koker MM, Kleer CG: P63 expression in Breast Cancer. A Highly Sensitive and Specific Marker of Metaplastic Carcinoma. Am J Surg Pathol. 2004, 28: 1506-15122. 10.1097/01.pas.0000138183.97366.fd.CrossRefPubMed

40.

Leibl S, Sommersacher A, Denk H, Moinfar F: Metaplastic Breast Carcinomas: Are they of Myoepithelial Differentiation? Immunohistochemical Profile of the Sarcomatoid Subtype Using Novel Myoepithelial Markers. Am J Surg Pathol. 2005, 29: 347-353. 10.1097/01.pas.0000152133.60278.d2.CrossRefPubMed

41.

Tse GM, Tan PH, Chaiwun B, Putti TC, Lui PC, Tsang AK, Wong FC, Lo AW: p63 is useful in the diagnosis of mammary metaplastic carcinomas. Pathology. 2006, 38: 16-20. 10.1080/00313020500444625.CrossRefPubMed

42.

Sitterding SM, Wiseman WR, Schiller CL, Luan C, Chen F, Moyano JV, Watkin WG, Wiley EL, Cryns VL, Diaz LK: Alpha B-crystallin: a novel marker of invasive basal-like and metaplastic breast carcinomas. Ann Diagn Pathol. 2008, 12: 33-40. 10.1016/j.anndiagpath.2007.02.004.CrossRefPubMed

Title: Diagnostic utility of snail in metaplastic breast carcinoma
Authors: Aziza Nassar
Nicole Sookhan
Marta Santisteban
Sandra C Bryant
Judy C Boughey
Tamar Giorgadze
Amy Degnim
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2010
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/1746-1596-5-76

At a glance: The STEP trials

Springer Medicine

Diagnostic utility of snail in metaplastic breast carcinoma

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2010

A case of mesothelial/monocytic incidental cardiac excrescence and literature review

Exophytic benign mixed epithelial stromal tumour of the kidney: case report of a rare tumour entity

Gadd45β expression in chondrosarcoma: A pilot study for diagnostic and biological implications in histological grading

Automatic measurement of epithelium differentiation and classification of cervical intraneoplasia by computerized image analysis

Ocular fundus manifestation of two patients following long-term chloroquine therapy: a case report

Prostate-specific antigen and hormone receptor expression in male and female breast carcinoma