Breast malignant, males, children

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Breast malignant, males, children

Breast cancer

Hormone receptors

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update February 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● Estrogen receptors (ER) have alpha and beta subtypes
● ER-alpha: “classic” functions of ER; may render breast epithelium susceptible to proliferative stimulation of estrogen; expressed in breast and endometrium; immunostains not specifically classified as ER-alpha or ER-beta are usually ER-alpha
● ER-beta: provides “housekeeping” functions; expressed in normal ovary and granulosa cells, carcinoma of breast, colon, prostate; values differ from ER-alpha in BRCA1 associated breast carcinoma (BMC Cancer 2008;8:100)

Features
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● Presence of estrogen (type alpha) and progesterone receptors correlates best with response to anti-estrogen treatment (tamoxifen or others) or chemotherapy
● Expression of ER-beta in ER-alpha negative breast cancer patients is an independent marker for favorable prognosis after adjuvant tamoxifen treatment (Clin Cancer Res 2007;13:1987, Hum Pathol 2001;32:113); may have prognostic value in ER+/PR+ patients (APMIS 2009;117:644)
● Otherwise, hormone expression correlates only weakly with prognosis; presence is associated with older age
● Endocrine therapy responsiveness is observed even with low expression of ER (1-5%)
● ER gene profiling (BMC Genomics 2008;9:239) or ER-beta mRNA (BMC Cancer 2007;7:131) may predict the 30-40% of ER+ tumors that will NOT respond to tamoxifen
● Immunostaining is done on paraffin fixed tissue (previously required fresh tissue)
● Recommended to fix tissue within 1 hour of receipt (Mod Pathol 2009;22:1457), and for at least 6 hours (for HER2, Arch Pathol Lab Med 2009;133:775)
● ER antibodies SP1 and 1D5 give similar results (Am J Clin Pathol 2009;132:396)
● Report % of tumor nuclei stained and intensity of staining (none, weak, moderate, strong)
● Note: tumor staining may be heterogeneous
● Note: must validate tumor protocols in each lab; SP2 antibody for PR may be less reliable (Am J Clin Pathol 2008;129:398)
● Compared to ER, PR staining adds only a limited amount of additional predictive information for response to hormonal therapy (Mod Pathol 2004;17:1545)
● Antigen retrieval techniques are required for ER if glyoxal fixative is used (Hum Pathol 2004;35:1058)
● Metastases to skin are often positive for androgen receptor, even if ER- and PR- (Mod Pathol 2000;13:119)
● ASCO/CAP recommendations for immunohistochemistry testing (Arch Pathol Lab Med 2010;134:930)

ER/PR positive tumors
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● Includes most colloid carcinomas, most well differentiated tumors, bcl2+ tumors
● ER+ tumors have lower microvessel density (Int Semin Surg Oncol 2007;4:22)

Micro images
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ER+ (strong)

ER alpha+

ER beta+

ER+ (weak)

ER negative tumors have high microvessel density (CD34 staining)

DCIS with ER and HER2 double immunostaining

PR+ tumor

PR+ in only a few cells

PR cytoplasmic staining is considered negative, Fig. B

PR membranous staining is considered negative, Fig. B

Contributed by Leica Microsystems, Biosystems Division:

Invasive ductal carcinoma - ER (6F11) with intense nuclear staining

Strong nuclear staining for PR

Additional references
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● Wikipedia (ER), Wikipedia (PR), US National Cancer Institute - Tutorial

ER/PR negative tumors

Clinical description
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● Tumors are usually moderate/poorly differentiated with axillary nodal metastases and poor prognosis (Arch Pathol Lab Med 2002;126:325)
● Includes metaplastic, adenoid cystic, apocrine and acinic cell carcinomas; also comedocarcinoma, medullary carcinoma and basal-like carcinoma (which are typically triple negative [ER, PR, HER2])
● Often occurs in premenopausal women
● 30% of primary operable breast cancers are ER negative; of these, 94% are high grade, 85% are invasive ductal NOS (Mod Pathol 2005;18:26)
● Amongst breast cancer subtypes, triple negative tumors have the worst overall survival and the worst disease free survival (Clin Med Res 2009;7:4)
● BRCA1 pathway dysfunction is found in a substantial proportion of basal-like and triple negative breast cancers and can be exploited therapeutically (e.g., inhibitors of the PARP enzyme and cross-linking agents, link)

Gross images
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Various images

Micro description for triple negative tumors (basal-like morphology)
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● Poorly differentiated with central fibrosis / necrosis
● Usually lymphoid stroma, pushing margin

Micro images
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CD10+ invasive ductal carcinoma (also ER-)

Various images

Image

Positive stains
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● More likely p53+, HER2+, EGFR+ than ER+ tumors (Mod Pathol 2005;18:26)
● Basal-like tumors (triple negative) are intensely CK5/6 positive (see image)
● Express one or more myoepithelial markers (CD10, S100, smooth muscle actin) more frequently than ER- tumors (47% vs. 8%, Mod Pathol 2004;17:646)

End of Breast malignant, males, children > Breast cancer > Hormone receptors

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