FAP-Associated Desmoid Fibromatosis: A Comparison to Their Sporadic Counterparts.
Wai Chin Foo, Chiara Colombo, David Whitting, Shorhae Hajibashi, Wei-Lien Wang, Dina Lev, Alexander J Lazar. The University of Texas, M.D. Anderson Cancer Center, Houston
Background: Desmoid fibromatosis (DF) is fibroblastic/myofibroblastic neoplasm. Most arise sporadically with β-catenin (CTNNB1) mutations, but some are associated with familial adenomatous polyposis (FAP) having mutations in the adenomatous polyposis coli (APC) gene. We reviewed the clinical features of FAP-DF and examined immunoreactivity with a select panel in FAP-DF, compared the two populations, and correlated these biomarkers with clinical behavior.
Design: From our database of 613 DFs, 51 clinically and/or molecularly confirmed FAP-DFs were found with FFPE tissue (25 available). They were formatted to a tissue microarray (TMA) and evaluated for their expression of β-catenin, cyclin D1, p53, and MIB-1. β-catenin staining was evaluated for nuclear and cytoplasmic intensity and distribution. For cyclin D1, p53, and MIB-1, percentage of nuclear staining was recorded. The results were compared to a previously characterized TMA of sporadic DF (213 specimens).
Results: FAP-DF showed nuclear staining for β-catenin (30%-90%; median, 80%; intensity: 10 high, 7 low; 8 core needle biopsies were excluded, see below). All 20 evaluable FAP-DFs showed both cyclin D1 (1%-20%; median, 5%) and p53 immunoreactivity (1%-60%; median, 20%). 16/21 evaluable FAP-DFs showed MIB-1 immunoreactivity (1%-5%; median 1%). For β-catenin staining, there was no statistically significant difference between sporadic and FAP-DF. There was significantly increased cyclin D1 (p<0.0001) and p53 (P<0.05) staining in FAP-DF. Clinically, 40/51 FAP patients had intrabdominal/abdominal wall DF that arose within a median of 3 years in the area of prior colonic surgery. 10 patients had extra-abdominal tumors unrelated to a surgical site. 18 patients had multiple DFs involving distinct sites.
Conclusions: While β-catenin levels were similar despite the known genetic differences in FAP-DFs and sporadic DFs, nuclear cyclin D1 encoded by a target gene of β-catenin and p53 (believed to be modulated by β-catenin signaling) are increased perhaps providing insight into molecular pathogenesis. This study underscores the usefulness of nuclear β-catenin immunoreactivity specifically in FAP-DF, as is now well-established for sporadic DF. In our experience, for reasons unclear, nuclear β-catenin immunoreactivity is often reduced or absent in needle biopsies (both sporadic and FAP-DF compared to resections), and represents an important false negative and potential diagnostic pitfall.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 18, Tuesday Morning