Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers

Ping Tang, Xi Wang, Linda Schiffhauer, Jianmin Wang, Patricia Bourne, Qi Yang, Andrew Quinn, Steven I. Hajdu

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Ductal carcinoma in situ (DCIS) is a group of heterogeneous lesions genetically, morphologically, and biologically. Recently, breast epithelium in the terminal ductal lobular unit has been sub-classified based on the expression of several cytokeratin markers as stem cells (CK5/6 +), luminal cells (CK8, CK18 +), and basal cells (CK14, CK17 +). In this study we describe the relationship between DCIS of different nuclear grades (non-high grade and high grade) and these cell origin markers. Fifty-three cases of non-high grade and 46 cases of high grade DCIS were selected, and representative sections from each case were stained with antibodies to these cytokeratin markers. High grade DCIS showed significantly higher rates of expression with stem and basal cell markers compared with non-high grade DCIS (p <0.05). The majority of DCIS, both high grade and non-high grade, expressed luminal cell markers (67% to 91%) and single type of cell origin marker (72% to 87%). High-grade DCIS more frequently co-expressed all three types of cell origin markers compared with non-high grade DCIS (p <0.05). In summary, a subset of high grade DCIS frequently rises from stem or/and basal cell populations; the subset is associated with poor prognosis in invasive breast carcinoma. Thus, these markers may be used to identify a potentially more aggressive subgroup of breast carcinoma at its pre-invasive stage (DCIS), and to manage it accordingly. Second, most DCIS express luminal cell markers, suggesting that malignant transformation occurs relatively late along the cell differentiation pathway, contrary to the traditional belief that most neoplasms arise from a more primitive stem cell population. Third, the majority of DCIS exclusively express one type of progenitor marker, indicating that in most incidences they may arise from a single progenitor population. Last, triple expression of all types of cell origin marker is frequently associated with high grade DCIS, suggesting that more complicated pathways are involved in these more aggressive lesions. Further studies are needed to delineate the relationships of cell origin markers in DCIS and invasive carcinoma to the clinical outcome.

Original languageEnglish (US)
Pages (from-to)16-22
Number of pages7
JournalAnnals of Clinical and Laboratory Science
Volume36
Issue number1
StatePublished - Dec 1 2006

Fingerprint

Carcinoma, Intraductal, Noninfiltrating
Cells
Keratins
Stem cells
Antibodies
Stem Cells
Breast Neoplasms
Population
Cell Differentiation

Keywords

  • Breast carcinoma
  • Ductal carcinoma in situ
  • Intraductal carcinoma
  • Nuclear grade

ASJC Scopus subject areas

  • Microbiology
  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology
  • Molecular Biology
  • Hematology
  • Clinical Biochemistry
  • Medical Laboratory Technology

Cite this

Tang, P., Wang, X., Schiffhauer, L., Wang, J., Bourne, P., Yang, Q., ... Hajdu, S. I. (2006). Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers. Annals of Clinical and Laboratory Science, 36(1), 16-22.

Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers. / Tang, Ping; Wang, Xi; Schiffhauer, Linda; Wang, Jianmin; Bourne, Patricia; Yang, Qi; Quinn, Andrew; Hajdu, Steven I.

In: Annals of Clinical and Laboratory Science, Vol. 36, No. 1, 01.12.2006, p. 16-22.

Research output: Contribution to journalArticle

Tang, P, Wang, X, Schiffhauer, L, Wang, J, Bourne, P, Yang, Q, Quinn, A & Hajdu, SI 2006, 'Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers', Annals of Clinical and Laboratory Science, vol. 36, no. 1, pp. 16-22.
Tang P, Wang X, Schiffhauer L, Wang J, Bourne P, Yang Q et al. Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers. Annals of Clinical and Laboratory Science. 2006 Dec 1;36(1):16-22.
Tang, Ping ; Wang, Xi ; Schiffhauer, Linda ; Wang, Jianmin ; Bourne, Patricia ; Yang, Qi ; Quinn, Andrew ; Hajdu, Steven I. / Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers. In: Annals of Clinical and Laboratory Science. 2006 ; Vol. 36, No. 1. pp. 16-22.
@article{62dc0dfcbc7a49869176749be30bf175,
title = "Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers",
abstract = "Ductal carcinoma in situ (DCIS) is a group of heterogeneous lesions genetically, morphologically, and biologically. Recently, breast epithelium in the terminal ductal lobular unit has been sub-classified based on the expression of several cytokeratin markers as stem cells (CK5/6 +), luminal cells (CK8, CK18 +), and basal cells (CK14, CK17 +). In this study we describe the relationship between DCIS of different nuclear grades (non-high grade and high grade) and these cell origin markers. Fifty-three cases of non-high grade and 46 cases of high grade DCIS were selected, and representative sections from each case were stained with antibodies to these cytokeratin markers. High grade DCIS showed significantly higher rates of expression with stem and basal cell markers compared with non-high grade DCIS (p <0.05). The majority of DCIS, both high grade and non-high grade, expressed luminal cell markers (67{\%} to 91{\%}) and single type of cell origin marker (72{\%} to 87{\%}). High-grade DCIS more frequently co-expressed all three types of cell origin markers compared with non-high grade DCIS (p <0.05). In summary, a subset of high grade DCIS frequently rises from stem or/and basal cell populations; the subset is associated with poor prognosis in invasive breast carcinoma. Thus, these markers may be used to identify a potentially more aggressive subgroup of breast carcinoma at its pre-invasive stage (DCIS), and to manage it accordingly. Second, most DCIS express luminal cell markers, suggesting that malignant transformation occurs relatively late along the cell differentiation pathway, contrary to the traditional belief that most neoplasms arise from a more primitive stem cell population. Third, the majority of DCIS exclusively express one type of progenitor marker, indicating that in most incidences they may arise from a single progenitor population. Last, triple expression of all types of cell origin marker is frequently associated with high grade DCIS, suggesting that more complicated pathways are involved in these more aggressive lesions. Further studies are needed to delineate the relationships of cell origin markers in DCIS and invasive carcinoma to the clinical outcome.",
keywords = "Breast carcinoma, Ductal carcinoma in situ, Intraductal carcinoma, Nuclear grade",
author = "Ping Tang and Xi Wang and Linda Schiffhauer and Jianmin Wang and Patricia Bourne and Qi Yang and Andrew Quinn and Hajdu, {Steven I.}",
year = "2006",
month = "12",
day = "1",
language = "English (US)",
volume = "36",
pages = "16--22",
journal = "Annals of Clinical and Laboratory Science",
issn = "0091-7370",
publisher = "Association of Clinical Scientists",
number = "1",

}

TY - JOUR

T1 - Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers

AU - Tang, Ping

AU - Wang, Xi

AU - Schiffhauer, Linda

AU - Wang, Jianmin

AU - Bourne, Patricia

AU - Yang, Qi

AU - Quinn, Andrew

AU - Hajdu, Steven I.

PY - 2006/12/1

Y1 - 2006/12/1

N2 - Ductal carcinoma in situ (DCIS) is a group of heterogeneous lesions genetically, morphologically, and biologically. Recently, breast epithelium in the terminal ductal lobular unit has been sub-classified based on the expression of several cytokeratin markers as stem cells (CK5/6 +), luminal cells (CK8, CK18 +), and basal cells (CK14, CK17 +). In this study we describe the relationship between DCIS of different nuclear grades (non-high grade and high grade) and these cell origin markers. Fifty-three cases of non-high grade and 46 cases of high grade DCIS were selected, and representative sections from each case were stained with antibodies to these cytokeratin markers. High grade DCIS showed significantly higher rates of expression with stem and basal cell markers compared with non-high grade DCIS (p <0.05). The majority of DCIS, both high grade and non-high grade, expressed luminal cell markers (67% to 91%) and single type of cell origin marker (72% to 87%). High-grade DCIS more frequently co-expressed all three types of cell origin markers compared with non-high grade DCIS (p <0.05). In summary, a subset of high grade DCIS frequently rises from stem or/and basal cell populations; the subset is associated with poor prognosis in invasive breast carcinoma. Thus, these markers may be used to identify a potentially more aggressive subgroup of breast carcinoma at its pre-invasive stage (DCIS), and to manage it accordingly. Second, most DCIS express luminal cell markers, suggesting that malignant transformation occurs relatively late along the cell differentiation pathway, contrary to the traditional belief that most neoplasms arise from a more primitive stem cell population. Third, the majority of DCIS exclusively express one type of progenitor marker, indicating that in most incidences they may arise from a single progenitor population. Last, triple expression of all types of cell origin marker is frequently associated with high grade DCIS, suggesting that more complicated pathways are involved in these more aggressive lesions. Further studies are needed to delineate the relationships of cell origin markers in DCIS and invasive carcinoma to the clinical outcome.

AB - Ductal carcinoma in situ (DCIS) is a group of heterogeneous lesions genetically, morphologically, and biologically. Recently, breast epithelium in the terminal ductal lobular unit has been sub-classified based on the expression of several cytokeratin markers as stem cells (CK5/6 +), luminal cells (CK8, CK18 +), and basal cells (CK14, CK17 +). In this study we describe the relationship between DCIS of different nuclear grades (non-high grade and high grade) and these cell origin markers. Fifty-three cases of non-high grade and 46 cases of high grade DCIS were selected, and representative sections from each case were stained with antibodies to these cytokeratin markers. High grade DCIS showed significantly higher rates of expression with stem and basal cell markers compared with non-high grade DCIS (p <0.05). The majority of DCIS, both high grade and non-high grade, expressed luminal cell markers (67% to 91%) and single type of cell origin marker (72% to 87%). High-grade DCIS more frequently co-expressed all three types of cell origin markers compared with non-high grade DCIS (p <0.05). In summary, a subset of high grade DCIS frequently rises from stem or/and basal cell populations; the subset is associated with poor prognosis in invasive breast carcinoma. Thus, these markers may be used to identify a potentially more aggressive subgroup of breast carcinoma at its pre-invasive stage (DCIS), and to manage it accordingly. Second, most DCIS express luminal cell markers, suggesting that malignant transformation occurs relatively late along the cell differentiation pathway, contrary to the traditional belief that most neoplasms arise from a more primitive stem cell population. Third, the majority of DCIS exclusively express one type of progenitor marker, indicating that in most incidences they may arise from a single progenitor population. Last, triple expression of all types of cell origin marker is frequently associated with high grade DCIS, suggesting that more complicated pathways are involved in these more aggressive lesions. Further studies are needed to delineate the relationships of cell origin markers in DCIS and invasive carcinoma to the clinical outcome.

KW - Breast carcinoma

KW - Ductal carcinoma in situ

KW - Intraductal carcinoma

KW - Nuclear grade

UR - http://www.scopus.com/inward/record.url?scp=33646502692&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646502692&partnerID=8YFLogxK

M3 - Article

VL - 36

SP - 16

EP - 22

JO - Annals of Clinical and Laboratory Science

JF - Annals of Clinical and Laboratory Science

SN - 0091-7370

IS - 1

ER -