VIEWS: 18 PAGES: 5 CATEGORY: Medicine POSTED ON: 7/14/2010
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.
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- email@example.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
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