Mammaglobin vs GCDFP-15: An Immunohistologic Validation Survey for Sensitivity and Specificity

Rohit Bhargava, MD1; Sushil Beriwal, MD2; David J. Dabbs, MD1

Disclosures

Am J Clin Pathol. 2007;127(1):103-113. 

In This Article

Abstract and Introduction

There are limited data that compare the usefulness of mammaglobin with gross cystic disease fluid protein-15 (GCDFP-15) in the identification of breast carcinomas. Whole tissue sections of 29 breast carcinomas with matched lymph node metastases and 63 breast carcinomas on tissue microarray were stained with mammaglobin cocktail and GCDFP-15 antibodies. In addition, tissue microarrays (US Biomax, Rockville, MD) containing 544 different human tumors were also stained with the mammaglobin antibody cocktail. Positive staining was seen in 67 (55.4%) of 121 breast carcinomas with mammaglobin and in 28 cases (23.1%) with GCDFP-15. In the majority of cases, the staining intensity and number of cells staining were higher with mammaglobin than with GCDFP-15. Positive mammaglobin staining was also seen in 44 (8.1%) of 544 nonbreast tumors. Mammaglobin is a more sensitive marker than GCDFP-15 for breast carcinoma; however, it lacks the specificity of GCDFP-15.

The mammaglobin gene sequence fragments were first isolated in 1994 by Watson and Fleming[1] using a modified differential display polymerase chain reaction technique. A novel full-length complementary DNA clone was isolated by the same authors in 1996, which they designated as mammaglobin-1 (MGB1).[2] Mammaglobin is a secretory protein that has a predicted molecular mass of 10.5 kd and shares a high degree of homology with the rat prostatic steroid-binding protein subunit C3, human Clara cell 10-kd protein, and rabbit uteroglobin.

The MGB1 gene has been mapped to chromosome 11q12.3-q13.1 by fluorescence in situ hybridization (FISH).[3] Chromosome 11q13 is frequently amplified in breast carcinomas, but gene amplification or gross rearrangements have not been detected in breast tumors or cell lines.[3] In contrast, mammaglobin protein overexpression has been found in breast carcinomas. Watson and Fleming[2] found that 8 (23%) of 35 primary breast carcinomas overexpressed MGB1 relative to normal breast tissue specimens. Watson et al[3] also found that 5 (50%) of 10 breast carcinoma cell lines and 13 (62%) of 21 metastatic breast tumors exhibited high levels of MGB1 messenger RNA. The overexpression did not seem to correlate with histology, tumor grade, tumor stage, or hormone receptor status. Recent studies have suggested that mammaglobin is specific for breast carcinoma and expression is associated with well-differentiated, receptor-positive tumors.[4,5,6,7]

However, mammaglobin has not been extensively studied by immunohistochemical analysis in human tissues. To define the sensitivity of mammaglobin expression in breast tumors and in other malignancies, we studied mammaglobin expression by immunohistochemical analysis in a variety of human tumors. We also compared mammmaglobin sensitivity with that of gross cystic disease fluid protein-15 (GCDFP-15).

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