[662] Low Grade Neuroendocrine Tumors Arising in Intestinal Adenomas: Evidence for Alterations in the Beta-Catenin/APC Pathway

Jeannelyn S Estrella, Melissa W Taggart, Asif Rashid, Susan C Abraham. U.T. M.D. Anderson Cancer Center, Houston, TX

Background: Although high grade/small cell neuroendocrine tumors (NETs) arising from intestinal adenomas are well-described, intestinal adenomas rarely give rise to low grade NETs; the largest series to date includes only 4 cases. Such lesions have occasionally been reported in patients with familial adenomatous polyposis (FAP), suggesting a role for the APC/beta-catenin pathway in composite adenoma/low grade NET.
Design: We identified 18 cases of composite adenoma/low grade NET arising in the colorectum (15) and duodenum (3). These cases were evaluated for size, depth of invasion, presence of other invasive elements (adenocarcinoma, squamous carcinoma), lymphovascular invasion, survival, and nuclear beta-catenin expression by immunohistochemistry. Beta-catenin staining was scored as % nuclear positivity multiplied by intensity (weak=1, moderate=2, strong=3), for a total possible score of 300. Control groups included 63 adenoma/high grade NET and 32 sporadic intestinal NET.
Results: Adenoma/low grade NETs ranged from 0.01-0.9 cm. NET alone comprised the invasive component in thirteen (72%) cases, whereas the other 5 also contained adeno- or squamous carcinoma. The NET component was confined to lamina propria in 5 (28%), muscularis mucosae in 5 (28%), and submucosa in 8 (44%). Only one showed lymphovascular invasion by NET, and all were alive without evidence of disease at last follow-up. Four (22%) patients had FAP. In comparison to sporadic low grade NET, adenoma/low grade NET had significantly higher beta-catenin expression (mean score of 231 vs 48, p>0.001). High levels of nuclear beta-catenin expression were also found in adenoma/high grade NET (mean score, 173) but were not significantly different from adenoma/low grade NET.

Adenoma/NET Characteristics
 Adenoma/low grade NET (n=18)Adenoma/high grade NET (n=63)p
Age63y (20-84y)58y (30-88y)NS
Gender (male)11 (61%)31 (49%)NS
Size0.4 cm (0.01-0.9 cm)4.3 cm (0.2-18 cm)0.004
Tumor components   
NET only13 (72%)45 (71%)NS
+ACA3 (17%)12 (19%)NS
+SCC1 (6%)5 (8%)NS
+ACA and SCC1 (6%)1 (2%)NS
Lymphatic invasion1 of 16 (6%)36 of 38 (95%)0.001
Lymph node metastasis0 of 5 (0%)28 of 34 (82%)0.001
Distant metastasis0 (0%)54 of 59 (92%)0.001
ACA, adenocarcinoma; SCC, squamous carcinoma


Conclusions: Low grade NETs arising in intestinal adenomas are generally small and indolent lesions. In contrast to sporadic low grade NETs, the occurrence of these lesions in patients with FAP and their high levels of nuclear beta-catenin expression support a role for the beta-catenin/APC pathway in their histogenesis.
Category: Gastrointestinal

Monday, March 19, 2012 1:00 PM

Poster Session II # 121, Monday Afternoon

 

Close Window