Haptoglobin (Hp) phenotypes were studied in 72 oesophageal and 104 gastric cancer patients and compared with 100 healthy controls to see if there is any association between oesophageal and gastric cancer and haptoglobin type.
Moreover, the presence of somatic APC mutations in fundic gland polyps suggests that inactivation of the APC gene plays a role not only in forming adenomas but also in forming hyperplastic polyps in fundic gland mucosa, and there may be some additional steps to the adenoma-carcinoma sequence.
We suggest that hyperplastic polyps are formed of a lineage that both synthesizes and secretes trefoil-peptides and the MUC1 mucin and that hyperplastic polyps may be related to the phenotypically similar ulceration-associated cell lineage.
Intestinal metaplasia, normal gastric mucosa, and 14/18 hyperplastic polyps were nonreactive. p53 Reactivity observed in four hyperplastic polyps was limited to adenomatous foci.
The enzyme activities of matrilysin were detected in cancer tissue and adenoma tissue, whereas they were hardly detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis, and normal colon tissue.
Expression of MUC1, MUC2, and MUC3 core tandem repeat proteins was examined in specimens of normal mucosa (n = 20), hyperplastic polyps (n = 10), adenomatous polyps (n = 89), and invasive cancer (n = 19).
Expression of MUC1, MUC2, and MUC3 core tandem repeat proteins was examined in specimens of normal mucosa (n = 20), hyperplastic polyps (n = 10), adenomatous polyps (n = 89), and invasive cancer (n = 19).
Expression of MUC1, MUC2, and MUC3 core tandem repeat proteins was examined in specimens of normal mucosa (n = 20), hyperplastic polyps (n = 10), adenomatous polyps (n = 89), and invasive cancer (n = 19).
A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps.
PCNA positivity gradually increased in the sequence from HP to AC and were significantly higher in AC compared to HP (90% vs 44%; p = 0.00007). p53 positive cells were found in 67% of AC while only occasionally in other groups (HP vs AC: p = 0.0002, AD (low dysplasia) vs AC: p = 0.001; AD (moderate dysplasia) vs AC: p = 0.001).
These results demonstrated a progressive immunoreactivity for PCNA in the HP to AC sequence, while p53 positivity and aneuploidy seemed specific for colon carcinoma.
Four patients had a germ-line E1317Q missense variant of APC that was not present in controls; one of these individuals had an unusually large number of metaplastic polyps of the colorectum.
Never-smokers showed no variation in risk across acetylator status for either species of polyp, whereas current smokers showed ORs of 2.0 (1.2-3.2) and 2.3 (1.4-3.9) for adenomas and 3.9 (2.1-7.1) and 4.9 (2.6-9.4) for hyperplastic polyps for slow and intermediate/fast NAT2, respectively, compared with slow-NAT2 never-smokers.
No significant differences were demonstrated between the Hp phenotypes in HDL cholesterol, apo A-I, apo E, Lp(a), cholesteryl esters, fibrinogen and C-reactive protein concentrations, although for the latter an increase was noticed in Hp 2-2.
Hyperplastic polyps and serrated adenomas of the colorectum show mixed gastrointestinal differentiation, expressing both gastric (M1 or MUC5AC) and intestinal (MUC2) mucins.
Four hamartomatous polyps (three from JP and one from PJS) showed seven, new mutations and one common APC variant (codon 486), whereas no hyperplastic polyps demonstrated mutation.
Four hamartomatous polyps (three from JP and one from PJS) showed seven, new mutations and one common APC variant (codon 486), whereas no hyperplastic polyps demonstrated mutation.
This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp.