Clinical decision making in Barrett's oesophagus can be supported by computerized immunoquantitation and morphometry of features associated with proliferation and differentiation

Grading of dysplasia in Barrett's oesophagus has a therapeutic impact, but subjective grading is associated with substantial observer variation. Quantitative pathological methods could help to achieve a more accurate and reproducible diagnosis. In the present study, the immunoquantitation of p53 and Ki67 and the morphometric analysis of features associated with proliferation and differentiation were evaluated for this purpose. In slides of 35 oesophagectomy specimens, 73 areas that displayed either no dysplasia (ND), low‐grade dysplasia (LGD), high‐grade dysplasia (HGD), or intramucosal carcinoma (ImCa) were initially considered. Agreement on double blind examination by two experienced pathologists was reached in 58 areas, which were used as the ‘learning set’. The 15 areas of disagreement were used as a second set. In the univariate analysis, the most significant differences in the learning set were found for Ki67, p53, stratification index (SI), mean nuclear area, and volume. Further multivariate analysis showed that for discrimination between ND and LGD, the combination of Ki67 and SI resulted in 94 per cent correctly classified areas. Likewise, for the discrimination between LGD and HGD, Ki67 and SI were the most powerful combination (again, 94 per cent of areas classified correctly). The discrimination between HGD and ImCa with any combination of the quantitative parameters never exceeded 80 per cent correct classification. The addition of p53 was of no value in improving the discrimination of ND vs. LGD, or of LGD vs. HGD. In the 15 original disagreement areas of the initial set of 73, three of the five ND/LGD areas could be uniquely classified as either ND or LGD by Ki67 and SI. Moreover, three of the four LGD/HGD disagreement areas could be uniquely classified with the combination of Ki67 and SI as either LGD or HGD. We conclude that the quantitative assessment of cytometric and morphometric features associated with proliferation and differentiation (especially Ki67 and SI) can be a valuable adjunct tool for clinical decision making in Barrett's oesophagus. © 1998 John Wiley & Sons, Ltd.

[1]  J. Peters,et al.  Outcome of adenocarcinoma arising in Barrett's esophagus in endoscopically surveyed and nonsurveyed patients. , 1994, The Journal of thoracic and cardiovascular surgery.

[2]  D. Brown,et al.  Which proliferation markers for routine immunohistology? A comparison of five antibodies. , 1994, Journal of clinical pathology.

[3]  The additional prognostic value of morphometric nuclear arrangement and DNA-ploidy to other morphometric and stereologic features in endometrial hyperplasias , 1993, International Journal of Gynecologic Cancer.

[4]  R. Lebovitz,et al.  p53 protein accumulation in Barrett's metaplasia, dysplasia, and carcinoma: a follow-up study. , 1993, Gastroenterology.

[5]  G. Meijer,et al.  Cytonuclear morphometry in assesment of dysplasia in polyps Pilot study , 1992 .

[6]  T. Rice,et al.  Surgical management of high-grade dysplasia in Barrett's esophagus. , 1993, The American journal of gastroenterology.

[7]  Patricia L. Blount,et al.  An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus. , 1993, Gastroenterology.

[8]  G. Tytgat,et al.  Does Endoscopic Surveillance in Esophageal Columnar Metaplasia (Barrett's Esophagus) Have Any Real Value? , 1995, Endoscopy.

[9]  V. Rusch,et al.  The management of high grade dysplasia and early cancer in Barrett's esophagus , 1994, Cancer.

[10]  D. Lane,et al.  Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. , 1990, The EMBO journal.

[11]  G. Meijer,et al.  Quantification of proliferative activity in colorectal adenomas by mitotic counts: relationship to degree of dysplasia and histological type. , 1995, Journal of clinical pathology.

[12]  D. Ransohoff,et al.  Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. , 1983, Human pathology.

[13]  Brian J. Reid,et al.  Flow-cytometric and histological progression to malignancy in Barrett's esophagus: Prospective endoscopic surveillance of a cohort , 1992 .

[14]  P. Blount,et al.  Evaluation of p53 protein expression in Barrett's esophagus by two-parameter flow cytometry. , 1992, Gastroenterology.

[15]  H Stein,et al.  Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. , 1984, Journal of immunology.

[16]  S. Steinberg,et al.  Expansion of the Ki‐67 proliferative compartment correlates with degree of Dysplasia in Barrett's esophagus , 1995, Cancer.

[17]  G. Offerhaus,et al.  Cell proliferation kinetics in the gastric remnant. , 1985, European journal of cancer & clinical oncology.

[18]  F. Ellis,et al.  Endoscopic surveillance of Barrett's esophagus. Does it help? , 1993, The Journal of thoracic and cardiovascular surgery.

[19]  P. Pairolero,et al.  Barrett's esophagus with high-grade dysplasia: an indication for esophagectomy? , 1992, The Annals of thoracic surgery.

[20]  S. Hamilton,et al.  POTENTIAL FALSE‐POSITIVE RESULTS WITH ANTIGEN ENHANCEMENT FOR IMMUNOHISTOCHEMISTRY OF THE p53 GENE PRODUCT IN COLORECTAL NEOPLASMS , 1996 .

[21]  B. Vogelstein,et al.  An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms , 1994, The Journal of pathology.

[22]  G Van Belle,et al.  Observer variation in the diagnosis of dysplasia in Barrett's esophagus. , 1988, Human pathology.

[23]  G. Tytgat,et al.  The value of p53 and Ki67 as markers for tumour progression in the Barrett's dysplasia-carcinoma sequence. , 1995, Surgical oncology.

[24]  F. B. Sørensen,et al.  Stereological Estimation of Nuclear Volume in Benign and Malignant Melanocytic Lesions of the Skin: Inter‐ and Intraobserver Variability of Malignancy Grading , 1991, The American Journal of dermatopathology.