Mammaglobin and CRxA-01 in pleural effusion cytology: potential utility of distinguishing metastatic breast carcinomas from other cytokeratin 7-positive/cytokeratin 20-negative carcinomas

Cancer. 2004 Dec 25;102(6):368-72. doi: 10.1002/cncr.20627.


Background: The most common causes of malignant pleural effusions in women are metastatic lung carcinomas and breast carcinomas. It is often very difficult to distinguish between breast carcinomas and other metastatic carcinomas when they share a similar morphology and a similar cytokeratin profile (CK7-positive/CK20-negative [CK7+/CK20-]). To better differentiate between metastatic mammary carcinomas and other metastatic carcinomas in pleural effusion cytology, the authors studied the potential use of a novel antibody, CRxA-01, which was identified by a cDNA subtraction library, together with a well characterized antibody against mammaglobin.

Methods: A computer search for patients with malignant pleural effusion specimens between January 1992 and November 2002 generated 228 patients, 71 of whom had cell block material and a known clinical history. Primary malignancies among these patients included 20 breast carcinomas, 32 lung carcinomas, 4 endometrial carcinomas, 9 ovarian carcinomas, 4 gastrointestinal carcinomas, and 2 genitourinary carcinomas. All specimens were immunostained with anti-CK7, CK20, CRxA-01, and mammaglobin antibodies. Only CK7-positive/CK20-negative (CK7+/CK20-) specimens were included in the current study, and only definitive membranous staining for CRxA-01 and cytoplasmic staining for mammaglobin were considered to be positive.

Results: For patients with metastatic breast carcinomas, mammaglobin was positive in 11 of 20 (55%) tissue specimens and CRxA-01 was positive in 12 of 20 (60%) tissue specimens. When CRxA-01 and mammaglobin were used together, 16 of 20 (80%) tissue specimens were positive for mammaglobin or/and CRxA-01 antibodies. This staining pattern was not seen for tissue specimens from patients with other metastatic carcinomas. Two of 4 (50%) uterine carcinoma specimens and 6 of 9 (67%) ovarian carcinoma specimens were positive for CRxA-01 only.

Conclusions: CRxA-01 and mammaglobin were expressed in most metastatic breast carcinoma specimens. Other CK7+/CK20- carcinoma specimens did not express mammaglobin and showed weak or negative staining for CRxA-01. When used together, CRxA-01 and mammaglobin greatly improved the sensitivity and specificity for the detection of metastatic breast carcinoma in pleural effusion specimens.

MeSH terms

  • Antibodies, Neoplasm / analysis*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / pathology*
  • Carcinoma / pathology*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / pathology*
  • Mammaglobin A
  • Neoplasm Metastasis
  • Neoplasm Proteins / analysis*
  • Pleural Effusion / cytology*
  • Sensitivity and Specificity
  • Uteroglobin / analysis*


  • Antibodies, Neoplasm
  • Biomarkers, Tumor
  • CRxA-01 antibody, human
  • Mammaglobin A
  • Neoplasm Proteins
  • SCGB2A2 protein, human
  • Uteroglobin