High Grade Serous and Endometrioid Carcinomas: A Convergence of Two Pathways in Pelvic Cancer Differentiation?
MH Roh, Y Yassin, A Miron, CP Crum, MS Hirsch. Brigham and Women's Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA
Background: Pelvic epithelial cancer is histologically diverse and the distinction between high grade serous and endometrioid carcinomas can be difficult. Recent reports indicate that a significant proportion of serous tumors arise from the distal fallopian tube, supported by the presence of a serous tubal intraepithelial carcinoma (STIC) +/- dominant ovarian mass (DOM), whereas endometrioid tumors typically present as a DOM in the absence of any known fallopian tube findings. This study analyzes the relationship between pelvic serous and endometrioid tumors using p53 and WT-1 immunohistochemistry and DNA sequencing for p53 mutations.
Design: Consecutive high grade pelvic serous and endometrioid carcinomas (grade 3) diagnosed in 2005-2007 were studied. The presence of a STIC and/or DOM in each case was determined and correlated with WT-1 and p53 expression by immunohistochemistry and the presence or absence of p53 mutations. Immunostaining was considered positive if more than 50% of the tumor cells exhibited nuclear staining for WT-1 or p53. Genomic DNA from laser capture microdissected tumor cells and control tissue was isolated and the exons 2-11 of p53 were amplified by polymerase chain reaction (PCR) and sequenced.
Results: 85 and 12 cases with a diagnosis of pure high grade serous or endometrioid carcinoma, respectively, were evaluated (fallopian tubes were entirely submitted for all cases). Of the 85 serous cancers, 3, 23, 27, and 32 cases were DOM+/STIC+, DOM+/STIC(-), DOM(-)/STIC+, and DOM(-)/STIC(-), respectively. 81/85 (95%) and 59/85 (69%) serous tumors were immunopositive for WT-1 and p53, respectively. Mutations in p53 were seen in 78/85 (92%) cases. Of the endometrioid carcinomas, none were STIC+ (p = 0.008). 9/12 (75%) were DOM+ and 3/12 (25%) were DOM(-)(p = 0.004). 9/12 (75%) were WT-1 positive (p = 0.04) and 7/12 (58%) were p53 positive (p > 0.05). Mutations in p53 were detected in 9/12 (75%) cases (p > 0.05).
Conclusions: High grade serous and endometrioid carcinomas have distinct patterns of growth and potential sites of origin (including the distal fallopian tube) based on the parameters of a DOM and/or STIC. However, these two subtypes of Mullerian carcinoma are marginally different based on WT-1 expression, and cannot be readily distinguished by p53 immunostaining or mutational status.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 177, Tuesday Afternoon