[1239] p53, WT1, and PAX8 Immunohistochemical Profiles in Ovarian Malignant Mesodermal Mixed Tumors

Keiyan Sy, Matthew Cesari, Sharon Nofech-Mozes, Zeina Ghorab, Nadia Ismiil, Valerie Dube, Mahmoud A Khalifa, Guangming Han. Sunnybrook Health Sciences Centre, Toronto, Canada

Background: Ovarian malignant mesodermal mixed tumors (MMMT) are rare but aggressive malignancies. Their immunohistochemical profiles and molecular characteristics are poorly characterized.
Design: 20 cases of MMMT (18 primary resections and 2 completion resections) from 2000-2012 were identified through our pathology database. All available slides were reviewed by two gynecologic pathologists. 1-2 representative slides with both carcinomatous (CC) and sarcomatous (SC) components were selected from each case. Nuclear stainings of three markers were scored semi-quantitatively and separately for CC and SC as follows: p53: null(n) (0%), wild(w) (1-75%), positive(p) (>75%); WT1: 0(0-5%), 1(6-50%), 2(>50%); PAX8: 0(0%), 1(1-25%), 2(26-50%), 3(>50%).
Results: The mean patient age was 65. 18/20 (90%) cases presented with stage III disease. 7/20 (35%) had neoadjuvant therapy. The CC in 16/19 cases (84.2%) were serous, 2/19 (10.5%) cases were endometrioid, 1/19 (5.3%) case was mixed serous and endometrioid. One completion oophorectomy had no CC remaining. The SC of 14/20 (70%) cases contained heterologous elements (7 chondrosarcoma, 6 rhabdomyosarcoma, and 1 with both elements). 6/20 (30%) cases had only homologous elements. Most cases showed concordant over-expression or null phenotype for p53 in both components (Table 1). One case with endometrioid CC showed wild-type p53 in CC, but overexpression in SC. The case with no residual CC was p53 wild-type in SC. 12/16 (75%) cases with serous CC demonstrated diffuse (>50%) WT1 staining. The cases of mixed and endometrioid CC were negative for WT1. None of the SC had >10% WT1 nuclear staining. However, 19/20 (95.0%) of the SC had strong cytoplasmic WT1. Diffuse (>50%) PAX8 was seen in CC in 78.9% of the cases, including 2 endometrioid type, but not in SC. Staining profiles between cases with heterologous and homologous elements were similar.

Table 1: Immunohistochemical profile of 20 ovarian MMMT cases
COMPONENTp53WT1PAX8
CARCINOMA (n=19)n= 8 (42.1%)0= 5 (26.3%)0 = 2 (10.5%)
 w= 1 (5.3%)1= 2 (10.5%)1 = 1 (5.3%)
 p = 10 (52.6%)2 = 12 (63.1%)2 = 1 (5.3%)
   3 = 15 (78.9%)
SARCOMA (n=20)n = 8 (40.0%)0 = 16 (80.0%)0 = 11 (55.0%)
 w = 1 (5.0%)1 = 4 (20.0%)1 = 7 (35.0%)
 p = 11 (55.0%)2 = 0 (0.0%)2 = 2 (10.0%)
   3 = 0 (0.0%)



Conclusions: The majority of CC display histologic and immunohistologic features similar to high-grade ovarian serous carcinoma. In most cases the SC shows concordant p53 staining with the CC but the WT1 and PAX8 staining are altered. This may suggest a common origin of carcinogenesis with high-grade serous carcinoma with divergent differentiation into sarcomatous elements.
Category: Gynecologic & Obstetrics

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 182, Wednesday Morning

 

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