Tubular adenomas with minor villous changes show molecular features characteristic of tubulovillous adenomas.
Advanced colorectal polyps are identified based on size ≥10 mm, high-grade dysplasia, and/or villous histology. A diagnosis of tubular adenoma (TA) is recommended if villous change occupies <20% of the lesion, or tubulovillous adenoma (TVA) is recommended if there is 20% to 80% villosity. We hypothesized that even subtle villous changes (1% to 20%) would correlate with advanced molecular features. Two hundred sixty-nine colorectal adenomas were examined for KRAS and BRAF mutation and immunohistochemical staining of β-catenin, O6-Methyl Guanine DNA Methyltransferase (MGMT), and p53. Adenomas were classified as TA1 (0% villosity, n=70), TA2 (1% to 20% villosity, n=81), or TVA (21% to 80% villosity, n=118). Clinical and molecular features were analyzed by univariate χ² and multivariate logistic regression. There was an incremental increase in KRAS mutation frequency with increasing villous compartment (17.9% TA1, 59.0% TA2, 78.4% TVA; P<0.001). MGMT was more frequently lost in TA2 (37.0%) than in TA1 (8.6%) (P<0.001) but did not differ from TVA (39.8%). p53 overexpression was more common in TA2 (38.3%) than in TA1 (10.0%) (P<0.001) but did not differ from TVA (32.2%). On multivariate analysis, TA2 adenomas were more likely to have a KRAS mutation [odds ratio (OR) 6.6, 95% confidence interval (CI), 3.0-14.2], MGMT loss (OR 6.2, 95% CI, 2.4-16.0), or p53 overexpression (OR 5.6, 95% CI, 2.3-13.7) than TA1. We have identified a subgroup of TAs based on subtle villous changes. These adenomas are more likely to show molecular features that are characteristic of TVAs than TAs. These data support the concept that any villous change may indicate increased malignant potential and may be useful to consider when assigning surveillance guidelines.
Royal Brisbane and Women's Hospital Research Foundation Clinical Research Centre, Brisbane, Australia.
Tatsuhiro
T
Ishii
Kenji
K
Notohara
Aarti
A
Umapathy
Kylie-Ann
KA
Mallitt
Hiroshi
H
Chikuba
Yukitoshi
Y
Moritani
Noriaki
N
Tanaka
Christophe
C
Rosty
Nagahide
N
Matsubara
Jeremy
J
Jass
Barbara
B
Leggett
Vicki
V
Whitehall
D018253:Adenoma, Villous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003111:Colonic Polyps / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics
D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D045643:DNA Repair Enzymes