P504S (AMACR-alpha-Methylacyl-coA Racemase): A Novel Marker of Clear Cell Carcinoma of the Female Genital Tract
Ramya P Masand, Anais Malpica, Michael T Deavers, Priya Rao, Preetha Ramalingam. MD Anderson Cancer Center, Houston, TX
Background: Clear cell carcinoma (CCC) of the female genital tract (FGT) poses a diagnostic challenge as its histologic features can overlap with other carcinomas particularly when they demonstrate clear cell change. Currently, CCC is diagnosed primarily on morphologic features with poor interobserver reproducibility. As yet, there are no specific immunohistochemical markers to assist in the diagnosis of CCC. P504S (AMACR-alpha-methylacyl-coA racemase) is widely used in the diagnosis of prostate cancer and papillary renal cell carcinomas. In addition, studies have show the expression of this marker in CCCs of the urinary bladder and urethra. However, P504S expression has not been extensively studied in tumors of the FGT, particularly CCC. The aim of our study is to determine if P504S is expressed by tumors of Müllerian origin with attention to its value, if any, in the diagnosis of CCC.
Design: 30 CCCs of FGT were retrieved from our pathology files covering a period of 26 years (1985 to the present). CCC from the following sites were included: endometrium (9), ovary (10), cervix (8), pelvis (1), vagina (1) and metastasis to a pelvic lymph node (1).13 serous carcinomas (SC), 15 endometrioid carcinomas (EC) of the endometrium and ovary, and 9 cases of endometriosis were used as controls. All cases were stained for P504S (Zeta Corp., Arcadia, CA). Granular cytoplasmic staining was interpreted as positive. Staining in the neoplastic cells was graded as follows: 0: no detectable staining, 1+: 1-5%, 2+: 6 to 25%, 3+: 26 to 50%, 4+: 51 to 75% and 5+: >76%.
Results: P504S was positive in 19 of 30 (70%) CCCs. Of these, 3 cases showed 1+, 4 showed 2+, 5 showed 3+, 3 showed 4+ and 6 showed 5+ staining for P504S. Only 1 of 13 (8%) SC was positive (1+) for P504S. Ten of 15 (67%) ECs were completely negative for P504S. Three of 5 ECs showed 1+ staining, 1 case showed 2+ staining and 1 case showed 5+ staining in the tumor cells. The positive staining of ECs, including the case with 5+ staining, was mostly confined to areas of necrosis and showed only weak to moderate intensity. None of the SC or EC showed strong diffuse staining for P504S.
Conclusions: We found that P504S is expressed in 70% of CCC of the FGT. Strong, diffuse, granular cytoplasmic staining of P504S, when present, is highly suggestive of CCC histotype. P504S is negative in majority of SC and EC and can be a useful marker to differentiate them from CCC, in challenging cases. Staining in areas of necrosis can be seen in SC and EC and must be interepreted with caution.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 186, Monday Morning