Analysis of Gene Mutations in Subtypes of Metaplastic Carcinoma of the Breast
Xiaoxian Li, Lei Huo, Stacy L Moulder, Michael Z Gilcrease. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Metaplastic carcinoma is a particularly aggressive subtype of triple-negative breast cancer that not only lacks targeted therapies but is generally resistant to standard chemotherapeutic regimens. The phosphoinositide 3-kinase (PI3K) signaling pathway is a potential therapeutic target in metaplastic carcinoma, as activating mutations in the PI3K catalytic subunit (PIK3CA) have been reported in up to 50% of metaplastic carcinomas. The frequency of PIK3CA and other gene mutations in specific subtypes of metaplastic carcinomas, however, is unclear.
Design: Paraffin-embedded tumor blocks from 20 cases of metaplastic carcinoma of the breast were retrieved from the surgical pathology archives in the Department of Pathology at the UT MD Anderson Cancer Center. Eleven of these were spindle cell sarcomatoid carcinomas, and 9 were matrix-producing carcinomas with cartilaginous matrix. DNA was extracted from each block following macrodissection, and a total 392 point mutations in 81 genes were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry developed by Sequenom for detection of single nucleotide polymorphisms.
Results: Sufficient DNA was obtained in 19 (95%) of the 20 cases. Ten of the 19 cases were spindle cell sarcomatoid carcinomas and the remaining 9 cases were matrix-producing carcinomas. Gene mutations in the PI3K signaling pathway were detected in 3 (30%) of the spindle cell sarcomatoid carcinomas and in 1 (11%) of the matrix-producing carcinomas. These included a mutation in FLT3, PIK3CA or AKT1 in each of the 3 spindle cell sarcomatoid carcinomas and a mutation in PIK3CA in the matrix-producing carcinoma. In addition, TP53 mutations were observed in 2 (22%) of the matrix-producing carcinomas but in none of the spindle cell sarcomatoid carcinomas.
Conclusions: These findings suggest that the prevalence of specific therapeutic targets in metaplastic carcinoma may vary according to histologic subtype. To our knowledge, this is the first report of a FLT3 mutation in spindle cell sarcomatoid carcinoma of the breast. As FLT3 is an upstream activator of both PI3K and MAPK pathways, dual pathway inhibition might be important in some of these tumors. Additional studies are needed to characterize more fully the range of mutations that occur in distinct subtypes of metaplastic carcinoma.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 27, Monday Morning