Transitional mucosa and survival in human colorectal cancer

Abstract

The mucosa in 100 segments of colon and rectum resected for cancer were examined using light microscopy and histochemical techniques. The extent of abnormal or transitional mucosa was defined for each case. Transitional mucosa was present in 93 of 95 adenocarcinomas and one malignant melanoma. The average total length of transitional change was 3.4 cm and the maximum length was 19.5 cm. An inverse correlation was observed between the survival and the length of transitional mucosa around locally invasive (Dukes' B) carcinomas (P = 0.005). This may be related to increased amounts of sialic acid in transitional mucosa and the ability of sialic acid to depress tumor immuno-genicity. The raised levels of sialic acids in transitional mucosa may have practical value in assessment of prognosis in colorectal cancer. Cancer 46:764-770, 1980. LTHOUGH THICKENED MUCOSA has been noted in A carcinoma of the large intestine for many years, only recently have the changes in this mucosa been clearly defined. Initially, attention was drawn to the histochemical changes. Increased amounts of sialo-mucins with a corresponding decrease in sulphated mucosubstances have been described. 10m~13 This thickened or "transitional" mucosa also shows subtle morphological abnormalities of crypt architecture on light microscopy. 13~14,29 Transmission electron microscopy has revealed an alteration in the relative proportions of the different epithelial cell types with persistence of immature and intermediate cells in the upper parts of the crypts as well as an overall increase in the number of goblet cells.6 Studies using scanning electron microscopy have shown structural alterations in the surface of transitional mucosa.26 Lipkin has shown abnormal proliferative characteristics in apparently normal mucosa surrounding colon carcinoma of both humans and animals in studies using tritiated thymidine. 21 In a small series, the amount of transitional mucosa in colorectal carcinoma appeared greater in more

Aberrant expression of intestinal mucin antigens associated with colorectal carcinoma defined by a panel of monoclonal antibodies

“…The anti-SIMA MAb 4D3 showed a tendency for stronger staining associated with a less malignant phenotype, namely carcinoma of stage A/B, smaller size, better differentiation. Both 4D3 and 10B3 positive tumours had a lower lymphocyte infiltrate, a feature previously reported for histologically-defined 'mucinous tumours' (Pihl, 1984) and interpreted as an indication that mucins may 'shield' cancers from the host immune response (Greaves et al, 1980). Over 90% of colorectal cancers contained mucin reactive with the two anti-LIMA MAb 2C3 and 9B5 in extracellular mucinous lakes or glandular lumen secretions as observed with the anti-SIMA MAb.…”

Histochemical alterations of mucin in normal colon, inflammatory bowel disease and colonic adenocarcinoma

“…Some investigators (Katsuyama et al, 1985;Reid et al, 1985) found a consistent reduction in the proportion of o-acyl sialic acid in colonic mucosa close to tumours, while in other studies (Rogers et al, 1978;Greaves et al, 1980) this change could not be detected. Additional reports (Lev et al, 1985;Muto et al, 1985;Sugihara & Jass, 1986) have suggested that sialic acid substitutions are a relatively common finding in a variety of disease states and are non-specific.…”

“…They include a variability in staining technique used in different laboratories (Williams, 1985) and a masking of one dye by another (McFadden et al, 1985). Despite these problems, sweeping conclusions have been drawn about the significance of HID/AB alterations in colonic disease, with some investigators finding the changes specifically associated with malignancy (Filipe, 1969;Filipe et al, 1980;Saffos & Rhatigan, 1977;Greaves et al, 1980;Shamsuddin et aI., 1981) and others considering them non-specific and reactive (Isaacson & Attwood, 1979;Listinsky & Riddell, 1981;Ehsanullah et al, 1982).…”

“…These include adenocarcinomas and the mucosa adjacent to adenocarcinomas (Reid et al, 1984;Katsuyama et al, 1985;Lev et al, 1985;Allen et al, 1988) as well as inflammatory conditions, such as diverticular disease (Reid et al, 1984), ulcerative colitis (Franzin et aI., 1983;Reid et al, 1984;Allen et al, 1988), Crohn's disease (Reid et al, 1984), and the solitary rectal ulcer syndrome (Listinsky & Riddell, 1981;Ehsanullah et al, 1982). Many studies have examined only the ratio of sulphomucins to sialic acid and relied exclusively on one technique, the high-iron diamine/Alcian Blue (HID/AB) reaction (Saffos & Rhatigan, 1977;Greaves et al, 1980;Shamsuddin et al, 1981;Listinsky & Riddell, 1981;Franzin et al, 1983;Allen et al, 1988). Most investigators identified a reduction in sulphomucins, particularly in transitional mucosa (Filipe, 1979), which was also morphologically dis-* Deceased 21 May, 1994.…”

“…0018-2214 9 1995 Chapman & Hall tinct and could be recognized by the presence of crypts that were dilated, deeper than normal and lined by abnormally tall columnar epithelium. Some studies found that sulphomucin loss was present predominantly in cancer-bearing colons and considered that transitional mucosa may be a carcinoma precursor (Filipe, 1969;Saffos & Rhatigan, 1977;Greaves et al, 1980;Shamsuddin et aI., 1981;Hill, 1983). In a majority of reports, however, investigators identified transitional mucosa in both neoplastic and non-neoplastic colons and concluded that it was probably reactive in origin (Isaacson & Attwood, 1979;Listinsky & Riddell, 1981).…”