Identification of MGB1 as a marker in the differential diagnosis of lung tumors in patients with a history of breast cancer by analysis of publicly available SAGE data

Abstract

The risk of developing second primary cancers is increased in patients with breast cancer. The lung is one of the major target organs, and therefore a differential diagnosis between primary and metastatic cancers is required for the treatment of lung tumors in patients with a history of breast cancer. However, biopsy specimens frequently result in small, fragmented tissues containing only a few, degenerated cancer cells. We attempted to find a useful marker for differential diagnosis, using the online SAGE database. We selected three molecules, small breast epithelial mucin (SBEM), prostate epithelium-specific Ets transcription factor (PDEF), and mammaglobin (MGB1), as potential markers for breast cancer. SBEM and PDEF proved of no use for practical differential diagnosis because they are expressed in the normal bronchus. In contrast, expression of MGB1 was detected in all 22 primary breast cancers, but not in 22 normal lung tissues. Furthermore, all 12 metastatic breast cancers examined demonstrated positive MGB1 transcripts, whereas one of 48 primary lung adenocarcinomas expressed MGB1. This suggests that MGB1 can serve as a differential molecular marker. In practice, prospective examination, using the nine cases with a history of breast cancer, confirmed the usefulness of MGB1 in differential diagnosis.

Figure 1

Expression analysis of potential breast-specific molecules (A) reveals that bulk tissue of normal lung (lane 1) expressed SBEM and PDEF, but not MGB1. Detailed examination using laser capture microdissection (lanes 2 to 4) demonstrated that bronchial surface epithelium and bronchial gland cells, but not the peripheral lung, were the source of the expression. In tumors (B), MGB1 expression was specific to breast cancers (B, lanes 9 to 15), with the notable exception of small-cell lung carcinomas (B, lane 8). DW indicates distilled water.

Figure 2

Practical application of MGB1 to an 80-year-old woman, who had a history of breast cancer 13 years previously. A lung tumor (A) and a lymph node of her left neck (B) were biopsied. In the lung tumor specimen, a few degenerated atypical cells are seen in the background fibrosis. Although the atypical cells are suggestive of an adenocarcinoma, it is impossible to determine whether the adenocarcinoma is primary or metastatic simply from HE sections (A). Positive staining of TTF-1 (C) and the absence of a transcript for MGB1 (D) suggests that this lung tumor is a primary pulmonary adenocarcinoma. By contrast, the metastatic cancer in the lymph node specimen is negative for TTF-1 and positive for MGB1 (D), suggesting metastatic breast cancer.