Mammaglobin Expression in Lymph Nodes Is an Important Marker of Metastatic Breast Carcinoma

Abstract

Abstract Context.—Organ specificity is a desirable property of a tumor marker, especially in metastatic adenocarcinomas of unknown primary origin. Mammaglobin, a mammary-specific member of the uteroglobin family, is known to be overexpressed in human breast cancer. Objective.—We investigated mammaglobin A expression in metastatic carcinomas of lymph nodes from the breast and various other organs and its usefulness in identifying metastatic carcinoma of the breast. For comparative purposes, we also investigated BRST-1 and BRST-2 expression. Design.—We produced recombinant mammaglobin and polyclonal antimammaglobin antibodies. Mammaglobin expression was analyzed by immunohistochemical staining using a tissue microarray and by reverse transcription–polymerase chain reaction in 210 carcinomas, including those of the breast (n = 70), lung (n = 30), stomach (n = 30), colorectum (n = 25), hepatobiliary tract (n = 20), urinary tract (n = 10), thyroid gland (n = 10), ovary and endometrium (n = 10), and salivary gland (n = 5). Results.—Mammaglobin expression was observed in 59 cases (84.3%) of breast cancer and in 21 cases (15.0%) of nonbreast cancer. The BRST-1 and BRST-2 expression rates were 75.7% and 44.3% in breast cancer and 26.4% and 2.1% in nonbreast cancer, respectively. Mammaglobin is superior to BRST-1 for both specificity and sensitivity and is superior to BRST-2 for sensitivity. Conclusion.—Our data suggest that mammaglobin is one of the first relatively mammary-specific and mammary-sensitive markers. Mammaglobin and BRST-2 appear to represent useful markers for breast cancer and should be used as a component of panels evaluating tumors of unknown primary sites.