Your Federal Quarterly Tax Payments are due April 15th Get Help Now >>

Basal-like Breast Carcinoma: A Phenotypically Distinct Entity by ProQuest

VIEWS: 18 PAGES: 5

Gene microarray profiling of human breast carcinomas has recently categorized invasive breast carcinomas into 5 distinct subtypes; luminal A, luminal B, normal breastlike, human epithelial growth factor receptor 2 (HER2) overexpressing, and basal-like. Basal-like breast carcinomas are characterized by high expression of basal cytokeratins; low or absent expression of estrogen receptor, progesterone receptor, and HER2/neu; and expression of epidermal growth factor receptor (EGFR) and/or c-kit, and they are frequently associated with breast cancer 1 (BRCA1) mutations and poor clinical outcome. Recent studies have begun to provide insights into the molecular genetics, biology, morphology, and clinical outcome of this subtype of breast carcinoma. We reviewed the literature related to basal-like breast carcinomas to better understand this clinically significant subtype of breast carcinoma.

More Info
									                                    Basal-like Breast Carcinoma
                                          A Phenotypically Distinct Entity
                                   Bisong Haupt, MD; Jae Y. Ro, MD, PhD; Mary R. Schwartz, MD

● Gene microarray profiling of human breast carcinomas                  es a distinct set of genes. Basal-like subtype was charac-
has recently categorized invasive breast carcinomas into 5             terized by high expression of cytokeratins (CKs) 5 and 17,
distinct subtypes; luminal A, luminal B, normal breastlike,            laminin, and fatty acid–binding protein 7, whereas HER2
human epithelial growth factor receptor 2 (HER2) over-                 overexpressing was characterized by high expression of
expressing, and basal-like. Basal-like breast carcinomas are           several genes in the ERBB2 amplicon at 17q22.24, includ-
characterized by high expression of basal cytokeratins; low            ing ERBB2 and GRB7 (Table). In this classification, tumors
or absent expression of estrogen receptor, progesterone re-            with the same gene expression pattern are grouped to-
ceptor, and HER2/neu; and expression of epidermal growth               gether, which provides a mechanism for studying the as-
factor receptor (EGFR) and/or c-kit, and they are frequent-            sociation of gene expression profiles with tumor mor-
ly associated with breast cancer 1 (BRCA1 ) mutations and              phology, biologic behavior, response to therapy, and clin-
poor clinical outcome. Recent studies have begun to pro-               ical outcome of patients.
vide insights into the molecular genetics, biology, mor-                  Gene expression profiling of tumors has not gained ac-
phology, and clinical outcome of this subtype of breast car-           cess to the clinical application. Morphology of basal-like
cinoma. We reviewed the literature related to basal-like               breast carcinomas is not unique and overlaps with many
breast carcinomas to better understand this clinically sig-            other subtypes of breast cancer. Many studies have tried
nificant subtype of breast carcinoma.                                   to define basal-like breast carcinoma using immunohis-
   (Arch Pathol Lab Med. 2010;134:130–133)                             tochemical methodology. Different criteria have been
                                                                       used. Some investigators defined basal-like breast carci-
                                                                       nomas as expressing at least one of the basal CKs (CK5,
B   reast cancer is one of the most common human neo-
      plasms, accounting for 22% of all cancers in women
worldwide.1 The incidence rate is higher in North Amer-
                                                                       CK14, and CK17)3–7 or a combination of 2 basal CKs
                                                                       (CK5/6 and CK14 or CK17).8,9 Others have included lack
                                                                       of expression of estrogen receptor (ER) and HER2/neu in
ica, Europe, and Australia than in the less developed re-              addition to expression of basal CKs, most commonly
gions of Africa and Southern and Eastern Asia. Breast can-             CK5/6,8 or lack of expression of ER, progesterone receptor
cer is a highly heterogeneous group of cancers, with di-               (PR), and HER2/neu and expression of one basal CK, epi-
versity in its morphology, molecular genetics, biology, and            dermal growth factor receptor (EGFR), and/or c-kit.9 Dif-
clinical outcome.                                                      ferent criteria used certainly affect the tumor composites
   Conventionally, invasive human breast carcinomas have               defined as basal-like breast carcinomas immunohistochem-
been classified morphologically into infiltrating ductal and             ically, and probably the prognostic significance observed.
lobular carcinoma, tubular carcinoma, mucinous carcino-                Precise criteria are now needed to standardize the clinical
ma, medullary carcinoma, invasive papillary carcinoma,                 studies on this group of tumors.
metaplastic carcinoma, and a few uncommon types. Re-                      In this paper, we have reviewed tumor cell origin, mor-
cently, gene expression profiling, a method using cDNA                  phology, immunophenotype, and clinical outcome of bas-
microarray to explore gene expression patterns, has clas-              al-like breast carcinomas for us to better understand this
sified breast cancer into 5 distinct subtypes based on var-             group of aggressive breast cancer.
iations in gene expression patterns. These 5 subtypes are
luminal A and luminal B, normal breastlike, human epi-                                   TUMOR CELL ORIGIN
thelial growth factor receptor 2 (HER2) overexpressing,                   The cell origin of breast carcinoma is unclear and has
and basal-like subtypes.2 Each subtype of tumors express-              been studied for decades. The main functional units of the
                                                                       human breast are terminal duct lobular units, which con-
  Accepted for publication March 16, 2009.                             tain 2 types of cells: luminal/glandular and basal/myo-
  From the Department of Pathology (Drs Haupt, Ro, and Schwartz)       epithelial. Luminal cells express CKs 7, 8/18, and 19; ER;
and Weill Medical College of Cornell University (Drs Haupt and Ro),    and epithelial membrane antigen. Basal/myoepithelial
The Methodist Hospital, Houston, Texas. Dr Haupt is now with the       cells express smooth muscle actin, p63, CK5/6, CK17, and
Department of Pathology, Saint Louis University, St Louis, Missouri.   CK14. The functional terminal duct lobular units can be
  The authors have no relevant financial interest in the products or
companies described in this article.
                                                                       generated after transplanting isolated epithelial cells from
  Reprints: Bisong Haupt, MD, Department of Pathology, Saint Louis     different regions of mammary glands into the cleared
University, 1402 S Grand Blvd, St Louis, MO 63104 (e-mail:             mammary fat pads of mice, which has led to the devel-
bisongxu@yahoo.com).                                                   opment of the mammary stem cell hypothesis.10
130 Arch Pathol Lab Med—Vol 134, January 2010                                                  Basal-like Breast Carcinoma—Haupt et al
            Gene Expression by Different Subtypes of                        ce
								
To top