Ovarian Carcinosarcomas: A Histomorphologic and Molecular Study
TL Mao, MC Lin. National Taiwan University Hospital, Taipei, Taiwan
Background: Ovarian carcinosarcomas (MMMTs) are malignant tumors with aggressive behavior. Based on the proposed pathogenetic model of ovarian tumors, MMMTs are type II tumors with high frequency of p53 mutation. To examine whether all ovarian MMMTs belong to type II, we studied the histomorphologic and molecular features of 11 MMMTs.
Design: The HE slides were reviewed by two pathologists. The carcinomatous and sarcomatous areas were separately microdissected followed by DNA extraction. Genes frequently mutated in ovarian carcinomas were analysed by direct sequencing. Immunohistochemistry for p53 and -catenin was also performed.
Results: The carcinomatous components included 5 high grade serous carcinomas, two grade 3 endometrioid carcinomas, two grade 1 endometrioid carcinomas, one clear cell carcinoma and one low grade serous carcinoma. Endocervical-like mucinous borderline tumor was present in one tumor with grade 3 endometrioid carcinoma. Choriocarcinoma was noted in one tumor with clear cell carcinoma. The sarcomatous components were heterologous in three tumors. Of the ten tumors with available DNA, p53 mutation was detected in 6 tumors. BRAF and PIK3CA mutations were found in the tumor with mucinous borderline tumor and grade 3 endometrioid carcinoma.
Table 1. Histomorphologic and molecular features of ovarian MMMTs in this studyND: not done
|Case||carcinoma||sarcoma||p53 stain||-catenin stain||p53 mutation||BRAF mutation||PIK3CA mutation|
|1||LG serous||homologous||+ in sarcoma||-||-||-||-|
|2||HG serous||chondrosarcoma||+||-||135 TGCTGG||-||-|
|3||MBT, gr 3 EM||homologous||+||-||272 GTGGGG||593 GATGGT||545 GCAGAA|
|4||HG serous||homologous||+||-||273 CGTCAT||-||-|
|6||HG serous||homologous||+||-||273 CGTCAT||-||-|
|7||gr 1 EM||homologous||-||+||-||-||-|
|8||gr 1 EM||rhabdomyosarcoma||+||-||220 TATTGT||-||-|
|9||HG serous||homologous||+||-||245 GGCGAC||-||-|
|10||clear cell||homologous||+ in sarcoma||-||-||-||-|
|11||gr 3 EM||chondrosarcoma||+||-||ND||ND||ND|
The corresponding sarcomatous components showed the same mutation. No mutation of KRAS or -catenin was detected. Nuclear staining of -catenin was seen in one tumor containing grade 1 endometrioid carcinoma. Positive expression of p53 was present except 3 tumors containing clear cell carcinoma, grade 1 endometrioid carcinoma and low grade serous carcinoma.
Conclusions: Our results revealed high frequency of p53 mutation in ovarian MMMTs, compatible with the pathogenetic model. A few MMMTs may derive from type I tumors. Presence of choriocarcinoma within one tumor suggests that tumor stem cells may occasionally acquire the potential of trophoblastic differentiation.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 162, Wednesday Morning