Table 2

Molecular alterations in baseline and sulindac-resistant adenomas

Molecular alterations in adenomas removed before treatment with sulindac (baseline) from patients with a complete response on sulindac (A) and sulindac-resistant patients (B) and in sulindac-resistant adenomas (C). Nuclear β-catenin, and epithelial and stromal Cox-2 expression were assessed in a semiquantitative manner, and the median and range (lowest and highest scores) are presented.

A: (n = 14)a Baseline adenomasB: (n = 9)a Baseline adenomasC: (n = 34) Resistant adenomasA compared with CB compared with C
Responsive patientsResistant patientsResistant patientsPP
Median (range)Median (range)Median (range)
Nuclear β-catenin3 (2–4)3 (3–4)2 (1–4)P = 0.002P < 0.001
Epithelial Cox-24 (1–4)3 (1–4)2 (1–4)P = 0.002P = 0.32
Stromal Cox-23 (1–4)3 (1–4)3 (1–4)P = 0.098P = 0.14
n/n tested (%)n/n tested (%)n/n tested (%) P P
Membranous β-catenin decreased11/13 (85%)9/9 (100%)13/34 (38%)P = 0.008P = 0.001
Cytoplasmic β-catenin overexpression12/13 (92%)7/9 (77%)33/34 (97%)P = 0.48P = 0.11
p53 overexpression5/13 (38%)2/9 (22%)6/34 (18%)P = 0.25P = 1.00
Bcl-2 overexpression11/13 (85%)6/9 (66%)25/34 (74%)P = 0.70P = 0.69
Bax loss of expression0/120/90/34
K-ras codon 12 mutation0/14 (0%)0/98/34 (24%)P = 0.09bP = 0.17b
LOH at 5q (APC locus)2/14 (14%)1/2 (50%)7/32 (22%)P = 0.70P = 0.42
MSI (Bat-26)0/140/90/34
  • a There were no statistically significant differences in any molecular parameter between A and B (P > 0.05).

  • b Overall, the difference in K-ras mutation rate between baseline adenomas (from sulindac-resistant and sulindac-responsive patients together) and resistant adenomas was statistically significant: P = 0.02.