Use of immunohistochemistry in the diagnosis of problematic breast lesions

Most diagnoses in breast pathology can be made with H&E sections. Nevertheless immunohistochemistry plays a useful supplementary role. This article reviews the common uses of immunohistochemistry in diagnostic breast pathology. It is important to be aware of the limitations of individual antibodies. Such problems can often be overcome by using panels of antibodies. Quality control is also essential: internal and external controls should show appropriate staining. Immunohistochemistry must be interpreted in combination with the morphology seen on H&E sections. Myoepithelial markers, such as smooth muscle actin, smooth muscle myosin heavy chain and p63, are useful for distinguishing invasive carcinoma from sclerosing lesions and ductal carcinoma in situ (DCIS), and in the classification of papillary lesions. Basal cytokeratins can help distinguish epithelial hyperplasia of usual type (UEH) and clonal proliferations such as DCIS and lobular carcinoma in situ (LCIS). UEH usually shows patchy expression whereas DCIS and other clonal proliferations are typically negative. E-cadherin can usually separate DCIS and LCIS: DCIS typically shows membrane staining and most LCIS is negative. Cytokeratins can be used to detect small nodal metastases or subtle invasive carcinomas such as invasive lobular carcinomas. Immunohistochemistry plays a useful role in diagnosing spindle cell lesions such as a panel of cytokeratins to identify spindle cell carcinomas. Immunohistochemistry is helpful in recognising metastases to the breast. Different antibodies are useful for different tumours: WT1 for ovarian carcinoma; TTF1 for pulmonary adenocarcinoma; S100, melan-A and HMB45 for melanoma; and lymphoid markers for lymphoma.