Related Experiment Videos
TAG-72 expression in primary, metastatic and hormonally treated prostate cancer as defined by monoclonal antibody
P C Brenner1, W J Rettig, M P Sanz-Moncasi
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Abstract:
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.
Insights
Monoclonal antibody CC49 targets tumor associated glycoprotein 72 (TAG-72). While TAG-72 is common in primary prostate cancer, its expression decreases in metastases, potentially impacting CC49 immunotherapy effectiveness.
Area of Science:
- Oncology
- Immunology
- Biomarker Research
Background:
- Monoclonal antibodies CC49 and B72.3 target tumor associated glycoprotein 72 (TAG-72), a marker related to sialylated Tn antigen.
- These antibodies have been utilized in clinical trials for imaging and treatment of various carcinomas, including prostate cancer.
Purpose of the Study:
- To investigate the expression of TAG-72 in primary, metastatic, and hormonally treated prostate cancer.
- To assess the suitability of TAG-72 as a target for CC49-based immunotherapies in advanced prostate cancer.
Main Methods:
- Immunohistochemical analysis using the CC49 antibody on 25 primary prostate carcinomas, 20 hormonally treated prostate cancers, and metastatic samples (lymph nodes, bone).
- Evaluation of TAG-72 expression across different Gleason scores and in prostatic intraepithelial neoplasia.
Main Results:
- TAG-72 expression was confirmed in 80% of primary prostate cancers, with varying levels across differentiation grades.
- TAG-72 expression was observed in 50% of hormonally treated prostate cancers but significantly reduced in lymph node metastases (17%) compared to bone metastases (50%).
- Prostatic intraepithelial neoplasia showed intense CC49 staining.
Conclusions:
- TAG-72 is frequently expressed in primary prostate cancer but shows diminished expression in lymph node metastases, suggesting potential limitations for CC49 immunotherapy.
- Pretreatment biopsy for TAG-72 expression may be crucial for optimizing patient selection in ongoing CC49 imaging and therapy studies.