The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 world health organization classification system

Jan P. Baak, George L. Mutter, Stanley Robboy, Paul J. Van Diest, Anne M. Uyterlinde, Anne Ørbo, Juan Palazzo, Bent Fiane, Kjell Løvslett, Curt Burger, Feja Voorhorst, René H. Verheijen

Research output: Contribution to journalArticle

Abstract

BACKGROUND. The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias. METHODS. A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had <1 year of follow-up. RESULTS. Twenty-four of 477 hyperplasias (5.0%) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354 nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3% in simple hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias, and 38% in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with <1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively). CONCLUSIONS. The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.

Original languageEnglish (US)
Pages (from-to)2304-2312
Number of pages9
JournalCancer
Volume103
Issue number11
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Fingerprint

Endometrial Hyperplasia
Hyperplasia
Disease Progression
Molecular Biology
Neoplasms
Endometrial Neoplasms
Multivariate Analysis
Regression Analysis

Keywords

  • Endometrial hyperplasia
  • Endometrial intraepithelial neoplasia
  • Progression
  • World Health Organization

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 world health organization classification system. / Baak, Jan P.; Mutter, George L.; Robboy, Stanley; Van Diest, Paul J.; Uyterlinde, Anne M.; Ørbo, Anne; Palazzo, Juan; Fiane, Bent; Løvslett, Kjell; Burger, Curt; Voorhorst, Feja; Verheijen, René H.

In: Cancer, Vol. 103, No. 11, 01.06.2005, p. 2304-2312.

Research output: Contribution to journalArticle

Baak, JP, Mutter, GL, Robboy, S, Van Diest, PJ, Uyterlinde, AM, Ørbo, A, Palazzo, J, Fiane, B, Løvslett, K, Burger, C, Voorhorst, F & Verheijen, RH 2005, 'The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 world health organization classification system', Cancer, vol. 103, no. 11, pp. 2304-2312. https://doi.org/10.1002/cncr.21058
Baak, Jan P. ; Mutter, George L. ; Robboy, Stanley ; Van Diest, Paul J. ; Uyterlinde, Anne M. ; Ørbo, Anne ; Palazzo, Juan ; Fiane, Bent ; Løvslett, Kjell ; Burger, Curt ; Voorhorst, Feja ; Verheijen, René H. / The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 world health organization classification system. In: Cancer. 2005 ; Vol. 103, No. 11. pp. 2304-2312.
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abstract = "BACKGROUND. The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias. METHODS. A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had <1 year of follow-up. RESULTS. Twenty-four of 477 hyperplasias (5.0{\%}) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13{\%}) and 8 of 354 nonatypical hyperplasias (2.3{\%}) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19{\%}) and 2 of 359 non-EINs (0.6{\%}) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3{\%} in simple hyperplasias, 22{\%} in complex hyperplasias, 17{\%} in simple atypical hyperplasias, and 38{\%} in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0{\%} in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92{\%}) better than WHO94 atypical hyperplasias collectively (67{\%}) or complex atypical hyperplasias alone (46{\%}). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with <1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively). CONCLUSIONS. The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.",
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AU - Mutter, George L.

AU - Robboy, Stanley

AU - Van Diest, Paul J.

AU - Uyterlinde, Anne M.

AU - Ørbo, Anne

AU - Palazzo, Juan

AU - Fiane, Bent

AU - Løvslett, Kjell

AU - Burger, Curt

AU - Voorhorst, Feja

AU - Verheijen, René H.

PY - 2005/6/1

Y1 - 2005/6/1

N2 - BACKGROUND. The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias. METHODS. A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had <1 year of follow-up. RESULTS. Twenty-four of 477 hyperplasias (5.0%) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354 nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3% in simple hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias, and 38% in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with <1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively). CONCLUSIONS. The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.

AB - BACKGROUND. The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias. METHODS. A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had <1 year of follow-up. RESULTS. Twenty-four of 477 hyperplasias (5.0%) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354 nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3% in simple hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias, and 38% in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with <1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively). CONCLUSIONS. The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.

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KW - Endometrial intraepithelial neoplasia

KW - Progression

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