Monoclonal antibodies CC49 and B72.3, which recognize a tumor associated glycoprotein (TAG-72) related to sialyted Tn antigen, have been used in clinical trials for radionuclide imaging, and treatment of colon, breast and ovarian carcinoma. In addition, studies with CC49 in patients with metastatic hormone refractory prostate cancer have been initiated based on the observed expression of TAG-72 in primary prostate cancer. We examined whether TAG-72 expression is a common feature of primary, metastatic and hormonally treated prostatic carcinoma. Immunohistochemical analysis of 25 primary prostatic carcinomas confirmed previous data that 21 of 25 specimens (80%) were immunoreactive with CC49. CC49 staining was noted in all 6 well (Gleason score 2 to 4), 8 of 10 moderately (Gleason score 5 to 6) and 7 of 9 poorly (Gleason score 7 to 9) differentiated tumors. CC49 immunoreactivity was noted in 10 of 20 hormonally treated prostate cancers and in 21 of 25 tumors without hormonal therapy. Intense CC49 staining of prostatic intraepithelial neoplasia was present in all 5 specimens examined. In contrast to the primary lesion, many metastatic prostate cancers lacked detectable CC49 immunoreactivity. Of 24 pelvic lymph node metastases from different patients only 4 (17%) had significant CC49 staining and 5 others had rare CC49 positive cells. However, 6 of 12 bone metastases showed CC49 immune staining. One specimen from an anaplastic locally recurrent tumor showed no reactivity. To our knowledge we present the first analysis of TAG-72 expression in a large series of patients with hormonally treated and metastatic prostate cancer, the most likely candidates for CC49 immunotherapy. Our findings that lymph node and bone metastases from prostate cancer are less likely to express significant amounts of TAG-72 than primary prostate cancer suggest that pretreatment biopsy typing for TAG-72 may be necessary to optimize the results of ongoing CC49 imaging and therapy studies.