Focus on Antibodies - July 2000

Myoepithelial Markers: An Aid in the Interpretation of Breast Biopsies 


As all surgical pathologists know, the distinction of invasive breast lesions from certain types of noninvasive lesions can be a difficult one, particularly on small needle biopsy samples. Studies have shown that invasive breast carcinoma lacks an associated myoepithelial layer on the periphery of the invasive nests of tumor cells, although this layer is intact or partially intact in benign lesions and CIS. Therefore, identification of an intact or partially intact myoepithelial layer in a breast lesion provides supportive evidence of a noninvasive process. In the past, smooth muscle actin (SMA) was often used for this purpose, but due to the extensive cross reaction of SMA with myofibroblasts, interpretation of SMA immunostains in a number of these types of cases was problematic.



Fig. 1: Smooth Muscle Myosin Immunostain on
normal terminal duct-lobular unit. The normal
myoepithelial layer is highlighted nicely.


Fortunately, there are several new markers of myoepithelial cells available (smooth muscle myosin heavy chains and calponin), that do not suffer from this
problem (Fig. 1), and for this reason they are extremely useful as aids in the interpretation of certain difficult breast biopsies. Below is an example of a case
where immunostains for smooth muscle myosin allowed a confident interpretation of a problematic case to be rendered.


Case Study 46 year-old female with a mammographic lesion underwent stereotactic needle biopsies of the breast. Pathologic examination revealed a background of fibrocystic change, and one focus that raised the possibility of tubular carcinoma (Fig. 2).



Fig 2: H&E sections of atypical ductal
proliferation in breast.


However, the examining pathologist was unsure based on morphology alone. For this reason, an immunostain for smooth muscle myosin heavy chains was requested, revealing an absent myoepithelial layer associated with the proliferating ducts of interest. (Figures 3-5). This finding provided strong evidence in support of the interpretation of tubular carcinoma, and allowed a definitive diagnosis of tubular carcinoma to be rendered.


Fig 3: Low power photomicrograph of smooth
muscle myosin immunostain, demonstrating
normal ducts and lobules on the left, with the
area of tubular carcinoma on the right.



Fig 4: Medium power photomicrograph of
myosin immunostain on tubular carcinoma. A
normal duct (with intact myoepithelial cells) and
a small blood vessel are noted on the right side
of the photograph, but myoepithelial cells are
absent from the area of tubular carcinoma.



Fig 5: High power photomicrograph of myosin
immunostain showing clear-cut absence of a
myoepithelial layer surrounding the neoplastic
ducts, with staining of the smooth muscle of an
adjacent blood vessel wall noted on the right,
serving as an internal positive control.


These new markers have been found to aid in the following differential diagnostic problems:

-- Radial Scar vs. Infiltrating Tubular Carcinoma
-- Cancerization of Sclerosing Adenosis by DCIS (mimicking invasive carcinoma)
-- Invasive Cribriform Carcinoma vs. DCIS
-- Adenoid Cystic Carcinoma vs. Collagenous Spherulosis or Cribriform DCIS
-- Papillary Carcinoma vs. Papilloma
-- Nipple Adenoma vs Infiltrating carcinoma.



Yaziji H, Gown, Am, Sneige N: Detection of Stromal Invasion in Breast Cancer: The Myoepithelial Markers. Advances in Anatomic Pathology 7 (2): 100-109, 2000.

Wang NP Wan BC, Skelly M et al: Antibodies to Novel Myoepithelium-Associated Proteins Distinguish Benign Lesions and Carcinoma Insitu from Invasive Carcinoma of the Breast. Applied Immunohistochemistry 5 (3): 141-151, 1997.