The role of myoepithelial cells
in breast disease.

N. Agnantis

The mammary myoepithelial cells form the outer layer in ducts and tubuloalveolar structures, surrounding the inner epithelial (luminal) cells and being surrounded by basement membrane. Due to their contractile ability they play an important role in milk ejection during lactation. They are also speculated to play a role in mammary development and tumorigenesis. The identity of myoepithelial precursor cell is not clear yet. Several data suggest the presence of a bipotent mammary progenitor cell, that can give rise to both luminal and myoepithelial cells
In hyperplasias the myoepithelia are admixed with the epithelial proliferation and play an active role in this process, since both cell types proliferate. The in situ carcinomas are neoplasms, and this fact implies a monoclonal expansion of one cell population, which results in a very monomorphic histologic appearance. One of the reasons for this apearance is that the myoepithelial cells are excluded from the neoplastic process.
The immunohistochemical detection of myoepithelial markers remains the optimal approach to distinguish between benign and malignant lesions. Thus, the presence of an intact outer myoepithelial layer characterizes all benign breast lesions, while continuous or focally discontinuous layer is noted in ductal carcinoma in situ. The hallmark of invasive carcinoma is the loss of the outer myoepithelial cell layer.
Several markers have been reported as ideal for highlighting myoepithelial cells: actin, SMM-HC, calponin, h-caldesmon, S-100 protein, keratins 5, 7, 14 and more recently maspin and CD10. Recent studies have demonstrated that myoepithelial cells also express p63, a nuclear protein homologous to p53. p63-positive myoepithelial cells have been noted surrounding benign epithelial lesions, and forming a consistent but discontinuous rim around epithelial cells of in situ carcinomas, while they are absent in invasive carcinomas. The pattern of p63-immunoreactivity is nuclear and so it is different from that observed with antibodies against cytoskeletal proteins, which is cytoplasmic. Results from our laboratory support the exhisting data that p63 can be useful in the distinction between adenosis and invasive ductal carcinoma, or between in situ and invasive carcinoma.p63 immunostaining could also be proved useful in the evaluation of intraductal papillary lesions.
The myoepithelial cells also express important regulatory molecules that are believed to regulate their development and differentiation, namely the Epidermal Growth Factor Receptor, Fibroblast Growth factor-2 (FGF2), members of the Wnt family and activin ?. In addition, it has been shown that the myoepithelial cells are necessary for the establishment and the maintenance of the mammary bilayer and that they have «tumor suppressor» potential.
Up to now we know very little about the cellular and molecular characteristics of the precursors of myoepithelial cells, and the mechanisms that regulate the myoepithelial phenotype and allow for the expression of a double identity (smooth muscle and epithelial). Furthermore, the nature of the signals that are involved in the interaction between epithelial and myoepithelial cells is largely unknown. These unanswered questions provide a wide field for future research.

N. J. Agnantis, MD, PhD,
FRC Path, AGE
Professor of Pathology,
President-Elect of ESP (2005-2007)
Director Department of Pathology, University of Ionnina Medical School,
Greece

 

Male breast cancer

I. Roisman

Breast cancer in men is a rare disease, accounting for approximately 1% of all breast cancer patients. Although the epidemiologic literature regarding female breast cancer is extensive, relatively little is known about the etiology of male breast cancer (MBC).
Major genetic factors associated with an increased risk of breast cancer for men include BRCA2 mutations, which are believed to account for the majority of inherited breast cancer in men, Klinefelter syndrome, and a positive family history. Suspected genetic factors include AR gene mutations, CYP17 polymorphism, Cowden syndrome, and CHEK2. Diseases with increased oestrogen action increase the risk of MBC. Mutations of distinct genes are estimated to account for up to roughly 10% of MBC. BRCA2 gene mutations are responsible for approximately 80% of the families with hereditary breast cancer. A family history of breast cancer poses higher risks for Jewish versus non-Jewish women, particularly for early-onset breast cancer. This appears to be due in large part to the high prevalence (2.5%) of three BRCA1 and BRCA2 founder mutations in Ashkenazi Jews.
About 4% to 8% of non-Jewish MBC patients versus 19% of Jewish MBC patients carry germline BRCA mutations. Jewish women are disproportionately impacted by BRCA mutations throughout life, with a 10% carrier rate for breast cancer diagnosed at any age and a 21% to 30% carrier rate for breast cnacer diagnosed by age 40. Comparable rates in non-Jewish populations are 6.1% for breast cancer diagnosed before age 50. We introduce our experience with MBC.
Between 2001 – 2004 we treated 43 men with breast cancer. One patient had bilateral breast cancer. The mean age was 64. 89% of the patients presented with breast mass. 77.3%, as in the literature, were invasive duct carcinoma, 68% were in stage I, and 11% were in stage IV. Modified radical mastectomy was the operation all the patients underwent. Five year survival were: stage I – 73%, stage II – 42%, stage III – 26%. We shall present in details our findings and discuss the literature.

I. Roisman1, I. Lifshitz2, G. Raphaeli3, O. Klem4,
I. Goldmann5, A. Bitterman5, Z. Kovacs5
1 Horev Medical Center, Haifa;
2 Kupat Holim Meuchedet, Jerusalem;
2 Hadassah Medical Center, Jerusalem;
4 Kupat Holim Meuchedet, Haifa;
5 Carmel Medical Center, Haifa,
Israel