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

Hertzog, Paul J.; Pilbrow, Simon J.; Pedersen, John; Polglase, A. L.; Lawson, Michael J.; Linnane, Anthony W.

doi:10.1038/bjc.1991.404

Cited by 14 publications

(17 citation statements)

References 19 publications

(21 reference statements)

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“…Secretory mucins show loss of sulphation and/or increased sialylation [32] and reduced Oacetylation of sialic acid [33]. The latter may relate to the demonstration of neuraminidase-sensitive small intestinal mucin antigen (SIMA) [23,34]. Despite these and other changes, transitional mucosa is generally regarded as a reactive process, since similar structural and functional alterations occur adjacent to metastases and in colorectal mucosa undergoing to prolapse [35].…”

Section: Transitional Mucosamentioning

confidence: 99%

Altered mucin expression in the gastrointestinal tract: a review

Jass

Walsh

2001

J Cellular Molecular Medi

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Early studies of changes in mucin expression in disorders of the gastrointestinal tract focused on alterations in the carbohydrate chain. This review briefly considers the various mechanisms by which such alterations may come about: (a) normal variation, (b) sialic acid alterations, (c) defective assembly of carbohydrate side-chains, (d) changed expression of core proteins and (e) epithelial metaplasia. The availability of monoclonal antibodies to mucin core proteins adds a new dimension to mucin histochemistry. It is now possible to offer explanations for traditional mucin histochemical findings on the basis of lineage-specific patterns of mucin core protein expression. Changes in core protein expression are described in inflammatory, metaplastic and neoplastic disorders of the gastrointestinal tract. The possibility that mucin change could be important in the aetiology of some diseases such as ulcerative colitis and H. pylori gastritis is considered. It is more probable, however, that changes in mucin expression are secondary to reprogramming of cellular differentiation and altered cell turnover. As such they may serve as markers to explain pathogenesis and provide novel diagnostic and prognostic information.

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Section: Transitional Mucosamentioning

confidence: 99%

Altered mucin expression in the gastrointestinal tract: a review

Jass

Walsh

2001

J Cellular Molecular Medi

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“…5 segments of normal large intes tine and 5 colorectal cancer specimens in 3 replicate determinations. Other antimucin MAbs used in this study included the anti-SIMA MAb 4D3 and anti-LIMA 2C3 [4], MAb 4AI with predominantly SIMA reactivity and 10B3 with both SIMA and LIMA reac tivity [5,6].…”

Section: Preparation and Immunochemical Characterization O F Monoclonmentioning

confidence: 99%

“…Microtiter plates were coated with 100 U/ml of SIMA [4], blocked with 1% BSA, then treated with 0.1-50 m M sodium metaperiodatc (Sigma) in 50 mM so dium acetate buffer, pH 4.5. for 1 h in the dark at room temperature, followed by 50 m.V/ NaBIU in PBS for 30 min at room temperature. Reactivity with serially diluted anti-SIMA MAbs was tested by a conventional indirect ELISA as previously described [4,5]. Coated antigens treated with acetate buffer and NaBH4 served as controls.…”

Section: Preparation and Immunochemical Characterization O F Monoclonmentioning

confidence: 99%

“…We have recently described the production of MAbs to small intestinal mucin antigen (SIMA) and large intestinal mucin antigen (LIMA), both high molecular weight mole cules with repeating epitopes, but antigenically and physicochemically distinct from each other [4], SIMA, an oncofetal antigen of the colon and a promising colorectal cancer marker, was undetectable in the normal adult colon but was detected in 94/100 colorectal cancers [4,5]. By contrast.…”

Section: Introductionmentioning

confidence: 99%

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Expression of a Novel Family of Epitopes on Small Intestinal Mucins in Colorectal Cancers, Adjacent and Remote Mucosa

Pilbrow

Hertzog²,

Pinczower³

et al. 1992

Tumor Biol

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We describe the production, immunochemical and immuno-histochemical characterization of monoclonal antibodies (MAbs) raised against the oncofetal small intestinal mucin antigen (SIMA). Four MAbs, reacting with distinct neuramini-dase-sensitive SIMA epitopes, were shown to define a novel differentiation-associated relationship of SIMA epitopes within the normal small intestinal villus. Using Swiss rolls of 15 entire colorectal cancer resections, inappropriate expression of SIMA epitopes was detected in all cancers, in adjacent transitional mucosa and remote morphologically normal mucosa, extending as far as resection margins (73%). SIMA expression, whether preexisting or reactive to the tumor, may predispose to malignant change and tumor recurrence.

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“…A previously described scoring method was used: a score of 0-3 was given for staining intensity and similarly, for distribution [0 (negative, 1 (<25% of crypt positive), 2 (25-75%) or 3 (75-100%)]. Aggregate scores (0-6) were obtained by adding the two scores (Hertzog et al, 1991b).…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

The adenoma-carcinoma sequence in the colorectum – early appearance of a hierarchy of small intestinal mucin antigen (SIMA) epitopes and correlation with malignant potential

Pilbrow

Hertzog²,

Linnane³

1992

Br J Cancer

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SummaryThe colorectal adenoma-carcinoma sequence was examined in relation to the ectopic expression of the oncofoetal Small Intestinal Mucin Antigen (SIMA), to the development of morphologic changes in the adenoma and perineoplastic mucosa and to indices of malignant potential. Four anti-SIMA MAbs, which define a novel hierarchy of SIMA epitopes in the normal small intestine and adjacent to colorectal cancers, were used in a retrospective immunohistochemical study of Familial Adenomatous Polyposis (FAP, n = 183) and non-familial (n = 44) adenomas. Inappropriate expression of SIMA epitopes was first detected in mucosa adjacent to minute microadenomas larger than three glands, and with increase in size, in increasing amounts within adenomas themselves, but not with microadenomas smaller than three glands or regions of flat mucosa free of adenomas. SIMA epitope expressed in mucosa adjacent to adenomas preceded changes in perineoplastic morphology, which progressed with adenoma growth to resemble transitional mucosa (TM) adjacent to cancers. Thus, the onset of both SIMA expression and morphological changes in TM were consistent with reactive rather than pre-existing field change phenomena. The previously reported hierarchy of four SIMA epitopes (5C5, 3D4, 4D3, 6C5) was also consistently observed in the adenoma-carcinoma sequence, and applied to (i) the order of epitope detection, (ii) the number of positive adenomas and (iii) extent of staining; (iv) the height in the crypt and (v) distance from the adenoma to which epitopes were expressed in perineoplastic mucosa. These observations are consistent with a progression of changes in mucin composition with adenoma development. The percentage of positive adenomas and reactivity scores for each anti-SIMA MAb correlated with increasing adenoma size, degree of dysplasia and growth pattern. SIMA expression appears to predate the earliest reported oncogene and tumour suppressor gene changes, was persistent and increased throughout adenoma development. SIMA epitopes are thus markers of very early neoplastic change, whose expression correlates with malignant potential and may contribute to the accumulation of changes necessary for tumourigenesis.

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

Cited by 14 publications

References 19 publications

Altered mucin expression in the gastrointestinal tract: a review

Altered mucin expression in the gastrointestinal tract: a review

Expression of a Novel Family of Epitopes on Small Intestinal Mucins in Colorectal Cancers, Adjacent and Remote Mucosa

The adenoma-carcinoma sequence in the colorectum – early appearance of a hierarchy of small intestinal mucin antigen (SIMA) epitopes and correlation with malignant potential

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