Best practice in diagnostic immunohistochemistry: prostate carcinoma and its mimics in needle core biopsies

The unrelenting challenge encountered when differentiating limited-volume prostate carcinoma and sometimes subtle variants from its many morphologic mimics has increased the use of ancillary immunohistochemistry in routine prostate needle biopsies. The availability of prostate cancer-associated and basal cell-associated markers has been an invaluable addition to diagnostic surgical pathology.

To review commonly used immunohistochemical stains, including innovative combinations, for confirmation or differential diagnosis of prostate carcinoma, and to propose appropriately constructed panels using morphologic patterns in prostate needle biopsies.

These best practices are based on our experience with routine and consultative case sign-outs and on a review of the published English-language literature from 1987 through 2008.

Basal cell-associated markers p63, high-molecular-weight cytokeratin 34 beta E12, cytokeratin 5/6 or a cocktail containing p63 and high-molecular-weight cytokeratin 34 beta E12 or cytokeratin 5/6 and prostate carcinoma-specific marker alpha-methylacyl coenzyme A (coA) racemase alone or in combination are useful adjuncts in confirming prostatic carcinoma that either lacks diagnostic, qualitative or quantitative features or that has an unusual morphologic pattern (eg, atrophic, pseudohyperplastic) or is in the setting of prior treatment. The combination of alpha-methylacyl coA racemase positivity with negative staining for basal cell-associated markers supports a malignant diagnosis in the appropriate morphologic context. Dual chromogen basal cell- associated markers (p63 [nuclear] and high-molecular-weight cytokeratin 34 beta E12/cytokeratin 5/6 [cytoplasmic]) and alpha-methylacyl coA racemase in an antibody cocktail provide greater sensitivity for the basal cell layer, easing evaluation and minimizing loss of representation of the focal area interest because the staining is performed on one slide. In the posttreatment setting, pancytokeratin facilitates detection of subtle-treated cancer cells. Prostate-specific antigen and prostatic acid phosphatase markers are helpful in excluding secondary malignancies involving the prostate, such as urothelial carcinoma, and occasionally in excluding nonprostatic benign mimickers, such as nephrogenic adenoma, mesonephric gland hyperplasia, and Cowper glands. There is no role for ordering immunohistochemistry prospectively in all cases of prostatic needle biopsies.