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Aberrations of the APC gene, which plays an important role in the genesis of familial adenomatous polyposis and colorectal carcinoma, were investigated in 31 surgical specimens of primary breast carcinoma. These studies utilized the polymerase chain reaction followed by restriction-fragment-length polymorphism and single-strand-conformation polymorphism analyses combined with tumor cell enrichment by cell sorting. Loss of heterozygosity at the APC locus was detected in 8 (38%) of 21 informative cases, but only 2 (6%) of 31 tumors carried a mutated APC gene. Direct DNA sequencing analysis confirmed mutations at codon 1081 (AGC to ATC) resulting in an amino acid substitution of serine for isoleucine, and at codon 1096 (CAG to CAT) resulting in a substitution of glutamine for histidine. There were no significant correlations between the loss of heterozygosity or mutation at the APC locus and any clinicopathological characteristics. Our present observations suggest that the mutations of the APC gene may play an important role in the genesis of certain breast carcinomas, and that another tumor-suppressor gene, which is the true target of frequent loss of heterozygosity, may exist near the APC gene.

Lymphoepithelioma-like carcinoma (LELC) is a tumor which occurs outside the nasopharynx and has morphological features identical to nasopharyngeal lymphoepithelioma. LELC of the breast (LELC-B) is uncommon, and its resemblance to medullary carcinoma of the breast (MC-B) obscures distinction between these two tumors. We report a case of LELC-B occurring in a 47-year-old woman. The tumor consisted of multinodules without circumscription. The tumor cells mainly exhibited loose clusters being permeated by numerous lymphocytes. The tumor cell clusters showed inconspicuous margins, which were far from syncytial patterns. The epithelial nature of the tumor cells was demonstrated by positivity for epithelial membrane antigen, AE1/AE3 and CAM5.2. Furthermore, glandular differentiation of the tumor cells was confirmed using electron microscopy for the first time. Epstein-Barr virus (EBV) was not detected using either in situ hybridization or polymerase chain reaction. These findings, together with former reports of LELC-B, suggest that the distinction between LELC-B and MC-B depends on whether circumscription and syncytial growth patterns exist. The other findings, including absence of EBV and immunohistochemical aspects of the tumor cells, are not considered different thus far. Although the prognosis of LELC-B is thought to be favorable, which is also similar to MC-B, distant metastasis was detected in the present case. To confirm the clinicopathological entity of these two tumors, it is important to recognize the difference between LELC-B and MC-B.

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Loss of heterozygosity (LOH) at the retinoblastoma (Rb) gene locus was investigated in 33 breast carcinomas by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis after tumor cell enrichment by cell sorting. The efficacy of cell sorting was evaluated by comparing the results of PCR-SSCP with and without cell sorting. Ten of 17 (59%) informative cases showed LOH at this locus by cell sorting combined with PCR-SSCP, although LOH was detectable in six (35%) cases without cell sorting. Flow cytometry and histologic examination revealed that this underestimation may occur when the tumor cell population is less than 50% in the specimens analyzed. It is concluded that LOH of the Rb gene occurs more frequently in human breast carcinoma than previously thought, and thus may contribute significantly to the development and/or progression of this tumor.