Computerized quantitative pathology for the grading of dysplasia in surveillance biopsies of Barrett's oesophagus

Decision models for surveillance of Barrett's oesophagus (BO) are governed by the grade of dysplasia on endoscopic biopsy, but subjective grading is prone to observer variation. Computerized morphometry and immunoquantitation can objectively discriminate between different grades of dysplasia in oesophagectomy specimens with BO. The present study evaluated the feasibility of such quantitative analysis on surveillance biopsies of BO. Biopsy criteria for quantitative analysis were defined, excluding 101 (21%) of 472 archival BO surveillance biopsies. In the remaining haematoxylin and eosin (H&E) sections, 105 areas that distinctively displayed no dysplasia (ND), low‐grade dysplasia (LGD) or high‐grade dysplasia (HGD) were demarcated. Agreement on double‐blind examination by two experienced pathologists was reached in 66 areas (63%; kappa: 0.44). For 21 ND/LGD and 11 LGD/HGD disagreement areas, corresponding sections for p53 and Ki67 immunohistochemistry were available. The best combination of two discriminating features was stratification index (SI) with p53 area % for ND versus LGD (89% correct classification), and SI with Ki67 area % for LGD versus HGD (91% correct classification). Fifteen of the 21 ND/LGD disagreement areas could be classified uniquely as either ND or LGD by SI and p53, and eight of the 11 LGD/HGD disagreement areas as either LGD or HGD by SI and Ki67. Correlation coefficients for repeated measurements of SI, Ki67, and p53 by the same observer were 0.94, 0.92, and 0.86, and by two independent observers 0.86, 0.93, and 0.92, respectively. Computerized quantitative pathology on BO surveillance biopsies is feasible provided that well‐defined biopsy criteria are used. Using a combination of features associated with cellular differentiation and proliferation, such as SI, p53, and Ki67, quantitative pathological analysis assists in reducing diagnostic variability in the grading of dysplasia during surveillance of BO. Copyright © 2000 John Wiley & Sons, Ltd.

[1]  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.

[2]  P. Blount,et al.  Flow-cytometric and histological progression to malignancy in Barrett's esophagus: prospective endoscopic surveillance of a cohort. , 1992, Gastroenterology.

[3]  G. Tytgat,et al.  Impact of endoscopic biopsy surveillance of Barrett’s oesophagus on pathological stage and clinical outcome of Barrett’s carcinoma , 1998, Gut.

[4]  J. Richardson,et al.  The rationale for esophagectomy as the optimal therapy for Barrett's esophagus with high-grade dysplasia. , 1996, Annals of surgery.

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

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

[7]  R. Goyal,et al.  The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. , 1996, Gastroenterology.

[8]  J. V. van Lanschot,et al.  Clinical decision making in Barrett's oesophagus can be supported by computerized immunoquantitation and morphometry of features associated with proliferation and differentiation , 1998, The Journal of pathology.

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

[10]  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.

[11]  G. Meijer,et al.  Cytonuclear morphometry in the assessment of dysplasia in colorectal adenomatous polyps. A pilot study. , 1992, Pathology, Research and Practice.

[12]  M. Gray.  Assessment of proliferation of squamous, Barrett's, and gastric mucosa in patients with columnar lined Barrett's oesophagus. , 1993, Gut.

[13]  D. Hopwood,et al.  Flow-cytometric analysis of growth-regulatory peptides and their receptors in Barrett's oesophagus and oesophageal adenocarcinoma. , 1992, Scandinavian journal of gastroenterology.

[14]  L. Bonelli.  Adenocarcinoma in Barrett's oesophagus. I: , 1993 .

[15]  G. Meijer,et al.  Reproducibility of p53 and Ki-67 immunoquantitation in Barrett's esophagus. , 1997, Analytical and quantitative cytology and histology.

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

[17]  P. Barbini,et al.  Gastric dysplasia: A stereological and morphometrical assessment , 1987, The Journal of pathology.

[18]  A. Smeulders,et al.  Cytomorphometry. A methodologic study of preparation techniques, selection methods and sample sizes. , 1989, Analytical and quantitative cytology and histology.

[19]  L. Jarvis,et al.  Morphometric analysis of gastric dysplasia , 1985, The Journal of pathology.

[20]  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.

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

[22]  P H Bartels,et al.  Knowledge-guided segmentation and morphometric analysis of colorectal dysplasia. , 1995, Analytical and quantitative cytology and histology.

[23]  P. V. van Diest,et al.  Systematic random sampling for selective interactive nuclear morphometry in breast cancer sections. Refinement and multiobserver evaluation. , 1993, Analytical and quantitative cytology and histology.

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

[25]  J. Peterse,et al.  Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project. , 1992, Human pathology.