Mammaglobin

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Stains & CD markers
Mammaglobin

Authors: Priyadharshini Sivasubramaniam, M.B.B.S., Julie M. Jorns, M.D.

Editorial Board Members: Christian M. Schürch, M.D., Ph.D., Kristen E. Muller, D.O.

Last author update: 24 June 2024

Last staff update: 20 September 2024

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Mammaglobin

Table of Contents

Cite this page: Sivasubramaniam P, Jorns JM. Mammaglobin. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsmammaglobin.html. Accessed December 21st, 2024.

Definition / general

Mammaglobin A expression is highly specific for tumors derived from the breast, female genital tract and salivary glands

Essential features

Mammaglobin A expression is observed in luminal epithelial cells of the breast and is frequently overexpressed in mammary carcinomas
Among normal tissues, the adult mammary gland has the highest expression (by far)
Tumor marker of mammary, gynecologic or salivary origin with diagnostic and prognostic applications

Terminology

Mammaglobin A (MAM A)
Secretoglobin family 2A member 2 (SCGB2A2)
Human mammaglobin (hMAG; hMAM)

Pathophysiology

Human mammaglobin A is a 10 kDa small secretory protein subtype belonging to the uteroglobin / Clara cell protein family (Diagnostics (Basel) 2023;13:1202)
Although the physiology is not well understood, mammaglobin A is thought to play a vital role in cell signaling and immune response (Int J Mol Sci 2023;24:13407)
Thought to transport steroid hormones that contribute to regulating hormone responsive tissue, like the breast (Diagnostics (Basel) 2023;13:1202)
Among normal tissues, mammaglobin A expression is predominantly seen in the adult breast, with lower expression in endocervical glands, endometrium and salivary glands (Diagnostics (Basel) 2023;13:1202)
Frequently upregulated in breast cancer, endometrioid cancer and some salivary gland tumors (Diagnostics (Basel) 2023;13:1202)

Clinical features

Mammaglobin A is a biomarker expressed in both primary and metastatic breast carcinomas, with greater expression in primary tumors
Positive reactivity is significantly associated with ER positive breast carcinomas
Has potential applications as a serum tumor marker and in noninvasive detection of lymph node metastasis (Int J Mol Sci 2023;24:13407)

Interpretation

Cytoplasmic and membranous staining patterns (Eur J Histochem 2022;66:3315)

Uses by pathologists

Highly specific for most breast cancers; useful for detecting circulating or metastatic breast cancer (Arch Pathol Lab Med 2003;127:1330, Int J Clin Exp Pathol 2009;2:384, Mod Pathol 2010;23:654)
- Superior to gross cystic disease fluid protein 15 (GCDFP-15) (Arch Pathol Lab Med 2008;132:239)
- Has limited utility in medullary and metaplastic breast cancers (Am J Clin Pathol 2012;137:747)
- Has limited utility in triple negative breast cancers (Eur J Histochem 2022;66:3315)
Useful to differentiate between cutaneous and mammary apocrine carcinomas (Hum Pathol 2014;45:320)
Positive in endometrial and endocervical specimens (benign and malignant) (Int J Gynecol Pathol 2008;27:418)
Highly sensitive marker for secretory carcinoma but less specific since it may be expressed in other salivary gland neoplasms (Hum Pathol 2013;44:1982)

Prognostic factors

In breast cancer (Int J Mol Sci 2023;24:13407, Eur J Histochem 2022;66:3315)
- Overexpression is predictive of bone metastases, reflecting its role as a marker of poor prognosis
- Overexpression is associated with tumor grade, lymph node status and Ki67 status
- High circulating mammaglobin A is associated with poor prognosis and is detected in 25% of cases with RT PCR
- Expression is associated with tumor infiltrating lymphocytes (CD8 positive and CD4 positive T cells)
- Downregulation has been linked to tumor progression
High grade endometrial adenocarcinomas have been shown to have loss of expression which is associated with poor prognosis (Oncol Lett 2020;20:255, Int J Surg Pathol 2020;28:631)

Microscopic (histologic) description

Cytoplasmic or membranous cell staining

Microscopic (histologic) images

Contributed by Julie M. Jorns, M.D.

Benign breast glands

Ductal carcinoma in situ

Invasive carcinoma, NST

Clear cell carcinoma ovary

Endometrioid carcinoma ovary

Positive staining - normal

Variable intensity staining pattern noted in the luminal cells of the breast (Diagnostics (Basel) 2023;13:1202)
Intense expression may be seen in endocervical glands but is not uniformly expressed in all glands (Diagnostics (Basel) 2023;13:1202)
Variable expression is present in the endometrium (Diagnostics (Basel) 2023;13:1202)
Moderate expression is seen in scattered epithelial cells of the fallopian tube (Diagnostics (Basel) 2023;13:1202)
Weak to moderate expression in the eccrine glands of the skin (Diagnostics (Basel) 2023;13:1202)
Weak to moderate expression in a few scattered cells in the salivary glands (Diagnostics (Basel) 2023;13:1202)

Positive staining - disease

Breast carcinoma (Semin Diagn Pathol 2022;39:313)
- Invasive breast carcinomas overall positivity in 50 - 70%
- Highest frequency of expression in luminal type invasive tubular and lobular carcinoma (Diagnostics (Basel) 2023;13:1202)
- Expression by biomarker profile
  - ER positive / HER2 negative breast carcinoma (50 - 80%)
  - HER2 positive breast carcinoma (50 - 60%)
Salivary gland neoplasms (Hum Pathol 2013;44:1982)
- Secretory carcinoma (100%, 15 of 15 cases) showed strong and diffuse expression
- Low grade cribriform cystadenocarcinoma (100%, 1 of 1 case) demonstrated strong and diffuse expression
- Salivary duct carcinoma (67%, 2 of 3 cases) displayed strong and diffuse expression
- Polymorphous low grade adenocarcinoma (67%, 2 of 3 cases) exhibited diffuse intense expression in one case versus focal and strong expression in another one

Negative staining

ER negative / HER2 negative breast carcinoma (9 - 30%)
Ovarian neoplasms: low positivity rates in high (14%) and low (6%) grade serous carcinomas
Mucoepidermoid carcinoma (11%, 2 of 18 cases) demonstrated strong and focal expression
Salivary gland neoplasms: acinic cell carcinoma (0%, 0 of 10 cases) adenoid cystic carcinoma (0%, 0 of 44 cases); pleomorphic adenomas (6%, 2 of 33 cases positive, with diffuse intense expression in one and focal weak expression in another case) (Hum Pathol 2013;44:1982)
Skin tumors: pilomatrixoma (0%, 0 of 32 cases), basal cell carcinoma (0%, 0 of 83 cases), benign nevus (0%, 0 of 29 cases), malignant melanoma (0%, 0 of 45 cases) and merkel cell carcinoma (0%, 0 of 41 cases), squamous cell carcinoma (2.2% weak positive) (Diagnostics (Basel) 2023;13:1202)
Female genital tract squamous cell carcinoma: vagina (0%, 0 of 73 cases), vulva (0%, 0 of 124 cases) and cervix (0%, 0 of 125 cases) (Diagnostics (Basel) 2023;13:1202)
Lung cancers: adenocarcinoma (0%, 0 of 176 cases), squamous cell carcinoma (0%, 0 of 69 cases), small cell carcinoma (0%, 0 of 16 cases) (Diagnostics (Basel) 2023;13:1202)
Others: cholangiocarcinoma, colonic adenocarcinoma, esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, germ cell tumors, hepatocellular carcinoma, lymphoma, melanoma, mesothelioma, pancreatic adenocarcinoma, prostatic adenocarcinoma, urothelial carcinoma, renal cell carcinoma, sarcoma, thymoma (Diagnostics (Basel) 2023;13:1202)

Molecular / cytogenetics description

Mammaglobin is found on chromosome 11q13, an area often amplified in breast cancer
Mammaglobin expression is influenced by transcriptional regulation mechanism (Oncogene 1998;16:817)
Potential of serum mammaglobin as a diagnostic biomarker for breast neoplasms has been reported to be encouraging but it needs additional validation (J Lab Physicians 2022;15:20)

Molecular / cytogenetics images

Images hosted on other servers:

Protumor and antitumor activities

Sample pathology report

Spine, T12, core biopsy:
- Positive for metastatic (lobular) breast carcinoma (see comment)
- Comment: Immunohistochemistry shows that metastatic carcinoma is positive for keratin 7, GATA3, mammaglobin and TRPS1 and negative for keratin 20 and E-cadherin, supporting the diagnosis.

Board review style question #1

Mammaglobin A is least frequently expressed in breast carcinomas with which biomarker profile?

Basal (ER negative, PR negative, HER2 negative)
HER2 (ER negative, PR negative, HER2 positive)
Luminal A (ER positive, PR positive, HER2 negative)
Luminal B (ER positive, PR negative, HER2 negative)

Board review style answer #1

A. Basal (ER negative, PR negative, HER2 negative). Mammaglobin A is least frequently expressed in basal-like or triple negative (ER negative, PR negative and HER2 negative) breast cancers, in which 30% or fewer will show mammaglobin A expression. Answers B, C and D are incorrect because mammaglobin A is frequently expressed in breast cancer, with highest expression among luminal types, followed by HER2 overexpressing breast cancer.

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Reference: Mammaglobin

Board review style question #2

In the setting of metastatic carcinoma to the bone, positive mammaglobin A immunohistochemistry is most suggestive of which primary site of origin?

Breast
Cervix
Lung
Ovary

Board review style answer #2

A. Breast. Mammaglobin A expression has the highest specificity for breast origin, particularly when diffuse and moderate to strong intensity; however, some cervical adenocarcinomas and ovarian carcinomas may express mammaglobin A. Answers B and D are incorrect because they are possible but less likely; these diagnoses may be considered, with appropriate correlation with clinical, morphologic and other immunophenotype features. Answer C is incorrect because lung carcinomas should not express mammaglobin A.

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Reference: Mammaglobin

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