Top

Published in:

01-09-2016 | Original Article

Expression of C-KIT, CD24, CD44s, and COX2 in benign and non-invasive apocrine lesions of the breast

Authors: Trine Tramm, Jee-Yeon Kim, Sebastian Leibl, Farid Moinfar, Fattaneh A. Tavassoli

Published in: Virchows Archiv | Issue 3/2016

Abstract

Benign apocrine metaplasia (AM) of the adult breast is a very common, but enigmatic lesion. It has been speculated that AM might be a precursor of malignancy or an indicator of a susceptibility of the breast tissue to develop neoplasia, mainly based on comparing the frequency of AM in breast cancer and non-breast cancer patients [1]. Studies using comparative genomic hybridization have supported this by showing similar molecular alterations in benign and malignant apocrine lesions [2]. Few studies, however, have compared expression of biomarkers involved in tumor progression in AM and progressively more advanced atypical apocrine lesions. The expression of C-KIT, COX2, CD24, and CD44s was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded material of 9 AM, 20 apocrine ductal intraepithelial neoplasia (DIN1c-3) and 40 atypical apocrine lesions (not qualifying for DIN1c-3) and compared to expression of the same biomarkers in adjacent normal ductal epithelium. Of the 66 apocrine lesions, 62 (94 %) did not express C-KIT compared to 4/63 (6 %) of the normal glands (Fisher’s exact, p < 0.001). COX2 was expressed in a significantly higher proportion of apocrine lesions than of normal glands (49 vs. 14 %, p < 0.001), and the number of apocrine lesions positive for CD24 was found to be higher with increasing aggressiveness of the lesions (Spearman, p < 0.001). In conclusion, benign and non-invasive proliferative apocrine lesions of the breast display immuno-phenotypical characteristics previously ascribed mainly to malignant transformation. This could lend support to the theory that AM is an early step towards malignant transformation, albeit associated with slow progression to carcinoma.

Available only for authorised users

Wellings SR, Alpers CE (1987) Apocrine cystic metaplasia: subgross pathology and prevalence in cancer-associated versus random autopsy breasts. Hum Pathol 18:381–386CrossRefPubMed

Jones C, Damiani S, Wells D, Chaggar R, Lakhani SR, Eusebi V (2001) Molecular cytogenetic comparison of apocrine hyperplasia and apocrine carcinoma of the breast. Am J Pathol 158:207–214CrossRefPubMedPubMedCentral

Haagensen DE Jr (1991) Is cystic disease related to breast cancer? Am J Surg Pathol 15:687–694CrossRefPubMed

Selim AG, Ryan A, El-Ayat G, Wells CA (2002) Loss of heterozygosity and allelic imbalance in apocrine metaplasia of the breast: microdissection microsatellite analysis. J Pathol 196:287–291CrossRefPubMed

Selim AG, El-Ayat G, Wells CA (2002) Expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast. Virchows Arch 441:449–455CrossRefPubMed

Elayat G, Selim AG, Wells CA (2010) Cell turnover in apocrine metaplasia and apocrine adenosis of the breast. Ann Diagn Pathol 14:1–7CrossRefPubMed

Elayat G, Selim AG, Wells CA (2009) Alterations of the cell cycle regulators cyclin D1, cyclin A, p27, p21, p16, and pRb in apocrine metaplasia of the breast. Breast J 15:475–482CrossRefPubMed

Cserni G (2008) Lack of myoepithelium in apocrine glands of the breast does not necessarily imply malignancy. Histopathology 52:253–255CrossRefPubMed

Tramm T, Kim JY, Tavassoli FA (2011) Diminished number or complete loss of myoepithelial cells associated with metaplastic and neoplastic apocrine lesions of the breast. Am J Surg Pathol 35:202–211CrossRefPubMed

10.

Yared MA, Middleton LP, Meric F, Cristofanilli M, Sahin AA (2004) Expression of c-kit proto-oncogene product in breast tissue. Breast J 10:323–327CrossRefPubMed

11.

Ulivi P, Zoli W, Medri L, Amadori D, Saragoni L, Barbanti F, Calistri D, Silvestrini R (2004) c-kit and SCF expression in normal and tumor breast tissue. Breast Cancer Res Treat 83:33–42CrossRefPubMed

12.

Natali PG, Nicotra MR, Sures I, Mottolese M, Botti C, Ullrich A (1992) Breast cancer is associated with loss of the c-kit oncogene product. Int J Cancer 52:713–717CrossRefPubMed

13.

Ko CD, Kim JS, Ko BG, Son BH, Kang HJ, Yoon HS, Cho EY, Gong G, Ahn SH (2003) The meaning of the c-kit proto-oncogene product in malignant transformation in human mammary epithelium. Clin Exp Metastasis 20:593–597CrossRefPubMed

14.

Matsuda R, Takahashi T, Nakamura S, Sekido Y, Nishida K, Seto M, Seito T, Sugiura T, Ariyoshi Y, Takahashi T (1993) Expression of the c-kit protein in human solid tumors and in corresponding fetal and adult normal tissues. Am J Pathol 142:339–346PubMedPubMedCentral

15.

Tsuura Y, Suzuki T, Honma K, Sano M (2002) Expression of c-kit protein in proliferative lesions of human breast: sexual difference and close association with phosphotyrosine status. J Cancer Res Clin Oncol 128:239–246CrossRefPubMed

16.

Celis JE, Gromov P, Moreira JM, Cabezon T, Friis E, Vejborg IM, Proess G, Rank F, Gromova I (2006) Apocrine cysts of the breast: biomarkers, origin, enlargement, and relation with cancer phenotype. Mol Cell Proteomics 5:462–483CrossRefPubMed

17.

Imada T, Matsuoka J, Nobuhisa T, Okawa T, Murata T, Tabuchi Y, Shirakawa Y, Ohara N, Gunduz M, Nagatsuka H, Umeoka T, Yamamoto Y, Nakajima M, Tanaka N, Naomoto Y (2006) COX-2 induction by heparanase in the progression of breast cancer. Int J Mol Med 17:221–228PubMed

18.

Hu M, Peluffo G, Chen H, Gelman R, Schnitt S, Polyak K (2009) Role of COX-2 in epithelial-stromal cell interactions and progression of ductal carcinoma in situ of the breast. Proc Natl Acad Sci U S A 106:3372–3377CrossRefPubMedPubMedCentral

19.

Ristimaki A, Sivula A, Lundin J, Lundin M, Salminen T, Haglund C, Joensuu H, Isola J (2002) Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62:632–635PubMed

20.

Kristiansen G, Winzer KJ, Mayordomo E, Bellach J, Schluns K, Denkert C, Dahl E, Pilarsky C, Altevogt P, Guski H, Dietel M (2003) CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res 9:4906–4913PubMed

21.

Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, Feleppa F, Huschtscha LI, Thorne HJ, kConFab, Fox SB, Yan M, French JD, Brown MA, Smyth GK, Visvader JE, Lindeman GJ (2009) Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 15:907–913CrossRefPubMed

22.

Celis JE, Cabezon T, Moreira JM, Gromov P, Gromova I, Timmermans-Wielenga V, Iwase T, Akiyama F, Honma N, Rank F (2009) Molecular characterization of apocrine carcinoma of the breast: validation of an apocrine protein signature in a well-defined cohort. Mol Oncol 3:220–237CrossRefPubMed

23.

Fogel M, Friederichs J, Zeller Y, Husar M, Smirnov A, Roitman L, Altevogt P, Sthoeger ZM (1999) CD24 is a marker for human breast carcinoma. Cancer Lett 143:87–94CrossRefPubMed

24.

Bircan S, Kapucuoglu N, Baspinar S, Inan G, Candir O (2006) CD24 expression in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study. Pathol Res Pract 202:569–576CrossRefPubMed

25.

Wang Z, Shi Q, Wang Z, Gu Y, Shen Y, Sun M, Deng M, Zhang H, Fang J, Zhang S, Xie F (2011) Clinicopathologic correlation of cancer stem cell markers CD44, CD24, VEGF and HIF-1alpha in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study. Pathol Res Pract 207:505–513CrossRefPubMed

26.

Afify A, McNiel MA, Braggin J, Bailey H, Paulino AF (2008) Expression of CD44s, CD44v6, and hyaluronan across the spectrum of normal-hyperplasia-carcinoma in breast. Appl Immunohistochem Mol Morphol 16:121–127CrossRefPubMed

27.

Tavassoli FA (1998) Ductal carcinoma in situ: introduction of the concept of ductal intraepithelial neoplasia. Mod Pathol 11:140–154PubMed

28.

Tavassoli FA, Norris HJ (1994) Intraductal apocrine carcinoma: a clinicopathologic study of 37 cases. Mod Pathol 7:813–818PubMed

29.

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983–3988CrossRefPubMedPubMedCentral

30.

Masood S, Rosa M (2009) The challenge of apocrine proliferations of the breast: a morphologic approach. Pathol Res Pract 205:155–164CrossRefPubMed

31.

Zagorianakou P, Zagorianakou N, Stefanou D, Makrydimas G, Agnantis NJ (2006) The enigmatic nature of apocrine breast lesions. Virchows Arch 448:525–531CrossRefPubMed

32.

Wells CA, El-Ayat GA (2007) Non-operative breast pathology: apocrine lesions. J Clin Pathol 60:1313–1320CrossRefPubMedPubMedCentral

33.

O’Malley FP, Bane AL (2004) The spectrum of apocrine lesions of the breast. Adv Anat Pathol 11:1–9CrossRefPubMed

34.

Wells CA, McGregor IL, Makunura CN, Yeomans P, Davies JD (1995) Apocrine adenosis: a precursor of aggressive breast cancer? J Clin Pathol 48:737–742CrossRefPubMedPubMedCentral

35.

Goto K (2015) Immunohistochemistry for CD117 (KIT) is effective in distinguishing cutaneous adnexal tumors with apocrine/eccrine or sebaceous differentiation from other epithelial tumors of the skin. J Cutan Pathol 42:480–488CrossRefPubMed

36.

Nishida H, Daa T, Kashima K, Arakane M, Urabe S, Yoshikawa Y, Gamachi A, Yokoyama S (2015) KIT (CD117) expression in benign and malignant sweat gland tumors. Am J Dermatopathol 37(12):898–905

37.

Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K (2010) Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res 16:876–887CrossRefPubMedPubMedCentral

38.

Moinfar F (2007) Essentials of diagnostic breast pathology: a practical approach. Springer, Germany

39.

Fuehrer N, Hartmann L, Degnim A, Allers T, Vierkant R, Frost M, Visscher D (2012) Atypical apocrine adenosis of the breast: long-term follow-up in 37 patients. Arch Pathol Lab Med 136:179–182CrossRefPubMedPubMedCentral

Title: Expression of C-KIT, CD24, CD44s, and COX2 in benign and non-invasive apocrine lesions of the breast
Authors: Trine Tramm
Jee-Yeon Kim
Sebastian Leibl
Farid Moinfar
Fattaneh A. Tavassoli
Publication date: 01-09-2016
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 3/2016
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-016-1966-1

At a glance: The STEP trials

Springer Medicine

Expression of C-KIT, CD24, CD44s, and COX2 in benign and non-invasive apocrine lesions of the breast

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2016

Book Review—Diagnostic pathology: soft tissue tumors, 2nd edition

Loss of expression of the SWI/SNF complex is a frequent event in undifferentiated/dedifferentiated urothelial carcinoma of the urinary tract

Micropapillary morphology is an indicator of poor prognosis in patients with urothelial carcinoma treated with transurethral resection and radiochemotherapy

The spectrum of ectopic thymomas

Nestin expression on tumour vessels and tumour-infiltrating macrophages define a poor prognosis subgroup of pt1 clear cell renal cell carcinoma

For staining of ALK protein, the novel D5F3 antibody demonstrates superior overall performance in terms of intensity and extent of staining in comparison to the currently used ALK1 antibody