Breast pathology, assessment of stromal invasion

• Collagen IV³ and laminin²: demonstrate basement membrane. Invasion occurs when malignant cells breach the basement membrane. However, invasive tumour may also synthesize basement membrane, rendering this approach of limited value.

Myoepithelial cells are present around non-invasive lesions but absent from invasive tumours. Various markers can be used to demonstrate them. Markers that stain myofibroblasts may be misinterpreted as staining myoepithelial cells, particularly if the myofibroblasts are flattened by adjacent nests of tumour cells. Similarly, immunoreactive blood vessels may become flattened and mimic myoepithelial cells. Genuine myoepithelial cells often show a slight bulging of the cytoplasm towards the epithelial cells and are accompanied by a lack of myofibroblasts in the surrounding stroma. It is generally easier to be confident of the presence of myoepithelial cells in benign lesion than to be confident of their genuine absence in invasive lesions. Using two markers may avoid misinterpretation; a combination of p63 and SMM-HC has been recommended¹.

	Marker	advantages	disadvantages
	Smooth muscle actin	strongly positive in myoepithelial cells: good highlighting of the architecture of small glandular proliferations, such as sclerosing adenosis	strongly positive in myofibroblasts in reactive stroma around invasive carcinoma, in blood vessels and rarely in scattered epithelial cells
	Calponin5	strong positivity in myoepithelial cells: less staining of myofibroblasts than with SMA	Stains blood vessels
	Smooth muscle myosin heavy chain (SMM-HC)5	much less staining of myofibroblasts than for SMA and calponin	slightly less sensitive than SMA and calponin, stains blood vessels
	HHF35		strong staining of epithelial cells4
	p63 (staining is nuclear)5,6	not expressed by myofibroblasts and blood vessels5,6: the best marker in the presence of reactive stroma	may appear discontinuous around some cases of DCIS; may stain epithelial cells, albeit weakly5,6
	S-100		often stains epithelial cells: not recommended4
	CD10	less staining of myofibroblasts than with SMA8; does not stain blood vessels8	less sensitive than other markers
	Cytokeratin 5: really more useful in differentiating UDH (positive) from ADH/DCIS/LCIS (negative)9		stains epithelial cells in usual ductal hyperplasia, low sensitivity for myoepithelial cells
	Maspin		can stain epithelial cells, limited data11
	WT-1		can stain epithelial cells, limited data12
	P-cadherin	strong staining of myoepithelial cells in ducts and lobules10: does not stain myofibroblasts10.	can stain epithelial cells and stromal cells10, limited data

		p63	Smooth muscle myosin heavy chain (SMM-HC)5	Calponin5
myoepithelial cells		85/855	85/855	85/855
	focal gaps around epithelium	9/855	6/855	1/855
myofibroblasts		0/855	7/855	65/855
vascular smooth muscle		0/855	85/855	85/855
luminal epithelial cells		9/85 (in only one case did the level of staining of epithelial cells approach that seen in myoepithelial cells)5	0/855	0/855

Rare types of invasive carcinoma show genuine myoepithelial differentiation. These include adenoid cystic carcinoma⁶, low-grade adenosquamous carcinoma^5,6, malignant adenomyoepithelioma⁵, malignant myoepithelioma and metaplastic (spindle cell) carcinoma. In particular, adenosquamous carcinoma may show peripheral staining of tumour nests for myoepithelial markers.

References

¹Lerwill, M. F. (2004). "Current practical applications of diagnostic immunohistochemistry in breast pathology." Am J Surg Pathol 28(8): 1076-91.

²Charpin, C., J. C. Lissitzky, et al. (1986). "Immunohistochemical detection of laminin in 98 human breast carcinomas: a light and electron microscopic study." Hum Pathol 17(4): 355-65.

³Willebrand, D., F. T. Bosman, et al. (1986). "Patterns of basement membrane deposition in benign and malignant breast tumours." Histopathology 10(12): 1231-41.

⁴Nayar, R., C. Breland, et al. (1999). "Immunoreactivity of ductal cells with putative myoepithelial markers: A potential pitfall in breast carcinoma." Ann Diagn Pathol 3(3): 165-73.

⁵Werling, R. W., H. Hwang, et al. (2003). "Immunohistochemical distinction of invasive from noninvasive breast lesions: a comparative study of p63 versus calponin and smooth muscle myosin heavy chain." Am J Surg Pathol 27(1): 82-90.

⁶Barbareschi, M., L. Pecciarini, et al. (2001). "p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast." Am J Surg Pathol 25(8): 1054-60.

⁷Yaziji, H., A. M. Gown, et al. (2000). "Detection of stromal invasion in breast cancer: the myoepithelial markers." Adv Anat Pathol 7(2): 100-9.

⁸Moritani, S., R. Kushima, et al. (2002). "Availability of CD10 immunohistochemistry as a marker of breast myoepithelial cells on paraffin sections." Mod Pathol 15(4): 397-405.

⁹Lacroix-Triki, M., E. Mery, et al. (2003). "Value of cytokeratin 5/6 immunostaining using D5/16 B4 antibody in the spectrum of proliferative intraepithelial lesions of the breast. A comparative study with 34betaE12 antibody." Virchows Arch 442(6): 548-54.

¹⁰Kovacs, A. and R. A. Walker (2003). "P-cadherin as a marker in the differential diagnosis of breast lesions." J Clin Pathol 56(2): 139-41.

¹¹Mohsin, S. K., M. Zhang, et al. (2003). "Maspin expression in invasive breast cancer: association with other prognostic factors." J Pathol 199(4): 432-5.

¹²Silberstein, G. B., K. Van Horn, et al. (1997). "Altered expression of the WT1 wilms tumor suppressor gene in human breast cancer." Proc Natl Acad Sci U S A 94(15): 8132-7.

This page last revised 11.9.2004.

©SMUHT/PW Bishop