Studies suggest that intestinal metaplasia of both the stomach and oesophagus may be a risk factor for the development of adenocarcinoma at these sites

Disappointing results have also been obtained when using the orcein/alcian blue and ruthenium red/alcian blue staining procedures. The former has shown either weak staining (also accompanied by background staining in many cases) or false staining patterns, particularly in sections that had undergone potassium permanganate pretreatment.

When the Leeds authors analysed

previous work on this subject, it was difficult to determine whether or not specimens were categorised according to the predominant type or, in the case of type III IM, merely on its presence. Thus, the frequencies expressed were open to question. For example, in a small group of gastric cancers (n=14), one group found type III in eight (57%) cases, but this was always in combination with another type of IM – type I in six cases, type II in one, and all three types in a further case. No indication of the predominant type present was given. No previous study at the time had assessed the relative proportions of the IM subtypes in cancer cases. The Leeds report showed that the frequency of type III (IIIa and IIIb) IM associated with gastric cancer (45%) was higher than those reported elsewhere. However, comparison of the frequency of types I and II showed no correlation between any of the results. While the amount of type I IM observed in the Leeds study was rather high, it appeared that the increased amount of this subtype was at the expense of type II. It is possible that some intervening cells were understained for sialomucin and thus false-negative cells were catagorised as type I.

Subtyping problems Previous subtyping of IM in Barrett’s oesophagus has also produced variable results. One study found the frequency of type III IM to be 60%, while another found it to be as high as 93.8%. The Leeds duo found type III (IIIa and IIIb) in 89% of cases, and as the predominant subtype in 78%. This revealed inherent

Intestinal metaplasia type IIIb. Goblet cells secrete either sulphomucin or sialomucin, while the intervening columnar cells are sulphomucin-positive (purple) (original magnification x40).

difficulties in the identification of IM subtypes because there are many variables and inconsistencies involved. Some sulphomucin-positive cells contain trace amounts only identifiable at high power, and the authors proposed a new classification to take account of this and the occasional difficulties in distinguishing ‘true’ goblet cells from vacuolated sialomucin-positive intervening columnar cells. Some areas of IM that were morphologically type I (ie goblet cells and absorptive cells) were sometimes seen to express sialomucins or sulphomucins in the intervening ‘absorptive-type’ cells, indicating categorisation as type II or III. With these problems in mind, it appears that the subtypes of IM cannot be placed into neat categories, as there is overlap in both distribution and development. It is evident that there are both ‘mosaics’ of different subtypes and transitional forms that are impossible to categorise. The existence of mosaic patterns has been emphasised previously when all combinations of IM subtypes present in 41% of 217 cases of gastric IM were reported. This provided additional evidence of impaired maturation and aberrant differentiation along various pathways that incorporated both small- and large-intestinal characteristics. The results of the Leeds study showed that the GAF/AB technique, using Sigma-Aldrich basic fuchsin, proved a suitable alternative to the HID/AB staining procedure for the discrimination of sulphomucins and sialomucins.


As previously suggested, type III IM is recognised by the presence of sulphomucins in intervening columnar cells, and could be used to help identify this subtype. However, the study also revealed that not all areas of IM can be classified in the clearly defined way that some authors have implied. Indeed, there are many variables and discrepancies involved in identifying the different subtypes. Therefore, the authors concluded that IM subtyping using histochemical analysis is a highly subjective procedure, open to varying interpretation. Consequently, previous work that has defined cancer risk based on the identification of metaplasia subtypes by mucin histochemistry should be viewed with caution.

Biomarker studies Oesophageal adenocarcinoma has a poor five-year survival rate (10–18%), and incidence has increased dramatically in the past three decades. Barrett’s oesophagus is the precursor lesion to cancer and is the replacement of the normally squamous lined oesophagus with columnar cells that develop an intestinal phenotype characterised by the presence of goblet cells. Given the known precursor state, oesophageal adenocarcinoma is amenable to screening and surveillance strategies (analogous to colon cancer). However, unlike colon cancer screening, Barrett’s poses challenges that make effective screening difficult. Robust and concerted effort is under way to find biomarkers.


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