Dysplasia in Barrett's oesophagus: p53 immunostaining is more reproducible than haematoxylin and eosin diagnosis and improves overall reliability, while grading is poorly reproducible.

AIMS: p53 immunostaining in Barrett's oesophagus (BO) has been shown to be predictive of progression, but data regarding its generalizability to routine practice are lacking. This study compared the reliability of p53 and dysplasia interpretation and grading. METHODS AND RESULTS: Seventy-two cases encompassing the full spectrum of BO were circulated to 10 pathologists from four institutions after a brief training session in p53 interpretation. Each pathologist classified cases on haematoxylin and eosin (H&E) alone using the Vienna classification and assessed the p53 staining using a qualitative system. Agreement was assessed using kappa statistics. For the four-tier Vienna system, the average unweighted kappa was 0.30. Weighted kappa values varied from 0.27 to 0.69 with an average of 0.47. When grouped into definite dysplasia versus no definite dysplasia the average kappa was 0.55, but the kappa for low-grade dysplasia (LGD) versus high-grade dysplasia (HGD) was only 0.31. For p53, using the three recognized patterns, the unweighted kappa was 0.6 (confidence interval 0.58-0.63). When cases were evaluated with both H&E and p53 the average kappa was 0.61 for definite dysplasia versus the rest. CONCLUSIONS: p53 immunohistochemistry interpretation is more reliable than dysplasia diagnosis, even with limited training. As it is predictive of prognosis and improves diagnostic reproducibility, it is suitable for routine use by pathologists as an adjunct to dysplasia diagnosis. The distinction of LGD versus HGD was poor. This study supports simplifying dysplasia diagnosis into 'present', 'indefinite' or 'absent', and the use of p53 as an ancillary marker in difficult cases. This should help to prevent overdiagnosis of dysplasia and inappropriate treatment.

Barrett's dysplasia and the Vienna classification: reproducibility, prediction of progression and impact of consensus reporting and p53 immunohistochemistry.

AIMS: The Vienna classification is used to classify dysplasia in Barrett's oesophagus (BO), but reproducibility and value of diagnosis of lower grades in particular are often questioned. The aim was to test the diagnostic variability and correlation with patient outcome and to attempt to define histological features causing discrepant diagnoses, as well as to test the impact of adding p53 immunohistochemistry on reproducibility and prediction of outcome. METHODS AND RESULTS: One hundred and forty-three patients with 154 sets of biopsy specimens originally diagnosed with Barrett's dysplasia were retrieved from the pathology records of Nottingham University Hospital. Thirty-two Barrett's patients without dysplasia were added. Anonymized slides were graded independently by five pathologists without and with p53-stained slides. Interobserver variation, correlation with outcome and diagnostic accuracy were determined. Weighted kappa scores between pairs of pathologists showed substantial agreement and improved after p53 immunohistochemistry. Agreement with the original diagnosis was substantially lower. Fourteen of 34 low-grade dysplasias (LGD) and 27 of 30 high-grade dysplasias on consensus progressed within 10 years compared with 18/94 and 28/39 of original diagnoses. Progression correlated with p53 positivity. CONCLUSION: The Vienna classification is useful and reproducible in BO. Consensus diagnosis by gastrointestinal pathologists produces high specificity and predictive value, even for LGD. p53 immunohistochemistry assists in diagnosis in difficult cases and predicts progression.