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PMID: 14580259 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Cell clusters overlying focally disrupted mammary myoepithelial cell layers and adjacent cells within the same duct display different immunohistochemical and genetic features: implications for tumor progression and invasion.

Breast cancer research : BCR ·Vol. 5 ·No. 6 ·2003-00-00 ·Pages R231-41

Man YG, Tai L, Barner R, Vang R, Saenger JS, Shekitka KM, Bratthauer GL, Wheeler DT, Liang CY, Vinh TN, Strauss BL

Abstract

Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale. Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by > or = 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability. Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers. Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation of a biologically more aggressive cell clone and the myoepithelial cell layer breakdown possibly associated with tumor progression or invasion.

MeSH Terms
Breast/chemistry,metabolism,pathology Breast Neoplasms/genetics,metabolism,pathology Carcinoma in Situ/genetics,metabolism,pathology Carcinoma, Ductal/genetics,metabolism,pathology Collagen Type IV/analysis DNA Mutational Analysis DNA, Neoplasm/chemistry,genetics Disease Progression Epithelial Cells/chemistry,metabolism,pathology Female Humans Immunohistochemistry Keratins/analysis Laminin/analysis Loss of Heterozygosity Microsatellite Repeats/genetics Muscle, Smooth/chemistry,metabolism,pathology Neoplasm Invasiveness Receptors, Estrogen/analysis,genetics
Chemicals
Collagen Type IV DNA, Neoplasm Laminin Receptors, Estrogen Keratins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Man Yan-gao
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology and American Registry of Pathology, Washington, DC, USA. man@afip.osd.mil
Tai Lisa
Barner Ross
Vang Russell
Saenger Jeffrey S
Shekitka Kris M
Bratthauer Gary L
Wheeler Darren T
Liang Chang Y
Vinh Tuyethoa N
Strauss Brian L
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Article Info
Journal
Breast cancer research : BCR
Abbr.
Breast Cancer Res
ISSN
1465-542X
DOI
10.1186/bcr653
Email
man@afip.osd.mil
Published
2003-00-00
Epub
2003-00-03
Pages
R231-41
Language
English
Region
England
NLM ID
100927353
PMCID
PMC314413
Subset
IM
External Links
PubMed source DOI: 10.1186/bcr653 PMC Full Text View journal details
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