Prognostic significance of E-cadherin protein expression in pathological stage I-III endometrial cancer

Loren K. Mell, Jeffrey Meyer, Maria Tretiakova, Andrey Khramtsov, Can Gong, S. Diane Yamada, Anthony G. Montag, Arno J. Mundt

Research output: Contribution to journalArticle

Abstract

Purpose: Decreased expression of E-cadherin in endometrial cancer cells is associated with adverse prognostic features. This study aimed to evaluate the prognostic significance of decreased E-cadherin expression in patients with endornetrial cancer. Experimental Design: Between 1992 and 1999, 102 endometrial cancer patients with stage I-III disease underwent primary surgery at the University of Chicago. Representative tissue specimens were immunostained with a monoclonal antibody to E-cadherin. A semiquantitative evaluation scale was developed based on the percentage of endometrial cancer cells with membranous E-cadherin staining. Tissue sections were scored as "3" if >75%, "2" if 25-75%, "1" if 5-25%, and "0" if <5% of cells stained. E-Cadherin staining was correlated with overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and extrapelvic progression. Multivariate Cox proportional hazards modeling was used to estimate hazard ratios, controlling for clinicopathological characteristics and adjuvant treatment. Median follow-up for the study group was 58.5 months. Results: E-Cadherin staining was scored as 0, 1, 2, and 3 in 29.4%, 18.6%, 26.5%, 25.5% of cases, respectively. E-Cadherin expression was positively correlated with myometrial invasion (Kendall τ: 0.30, P < 0.01), and negatively correlated with grade (Kendall τ: -0.13, P = 0.15) and papillary serous or clear cell histology (Kendall τ: -0.14, P = 0.12). Five-year actuarial OS, CSS, PFS, and extrapelvic recurrence rates for negative (score = 0), heterogeneous (score = 1-2), and positive (score = 3) staining were as follows: OS, 69.2 versus 75.7 versus 81.0% (P = 0.64); CSS, 78.8 versus 91.2 versus 95.5% (P = 0.19); PFS, 69.1 versus 88.6 versus 92.2% (P = 0.079), and extrapelvic progression, 20.8 versus 7.3 versus 4.0% (P = 0.17). On multivarlate Cox regression, a higher E-cadherin expression score was associated With decreased overall mortality [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.34-1.03; P = 0.066), and statistically significant decreases in endometrial cancer mortality (HR, 0.23; 95% CI, 0.055-0.94; P = 0.040), disease progression (HR, 0.28; 95% CI, 0.10-0.77; P = 0.014), and extrapelvic recurrence (HR, 0.24; 95% CI, 0.062-0.97; P = 0.045). Conclusions: Decreased E-cadherin expression is an independent prognostic factor for disease progression and mortality in pathological stage I-III endometrial cancer. Evaluation of E-cadherin expression may aid in the selection of patients for more aggressive adjuvant therapy.

Original languageEnglish (US)
Pages (from-to)5546-5553
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number16
DOIs
StatePublished - Aug 15 2004
Externally publishedYes

Fingerprint

Cadherins
Endometrial Neoplasms
Proteins
Survival
Confidence Intervals
Staining and Labeling
Disease-Free Survival
Disease Progression
Mortality
Recurrence
Patient Selection
Histology
Research Design
Monoclonal Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prognostic significance of E-cadherin protein expression in pathological stage I-III endometrial cancer. / Mell, Loren K.; Meyer, Jeffrey; Tretiakova, Maria; Khramtsov, Andrey; Gong, Can; Yamada, S. Diane; Montag, Anthony G.; Mundt, Arno J.

In: Clinical Cancer Research, Vol. 10, No. 16, 15.08.2004, p. 5546-5553.

Research output: Contribution to journalArticle

Mell, LK, Meyer, J, Tretiakova, M, Khramtsov, A, Gong, C, Yamada, SD, Montag, AG & Mundt, AJ 2004, 'Prognostic significance of E-cadherin protein expression in pathological stage I-III endometrial cancer', Clinical Cancer Research, vol. 10, no. 16, pp. 5546-5553. https://doi.org/10.1158/1078-0432.CCR-0943-03
Mell, Loren K. ; Meyer, Jeffrey ; Tretiakova, Maria ; Khramtsov, Andrey ; Gong, Can ; Yamada, S. Diane ; Montag, Anthony G. ; Mundt, Arno J. / Prognostic significance of E-cadherin protein expression in pathological stage I-III endometrial cancer. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 16. pp. 5546-5553.
@article{d3f10c07a319424e9b44ffd62b3e0ef3,
title = "Prognostic significance of E-cadherin protein expression in pathological stage I-III endometrial cancer",
abstract = "Purpose: Decreased expression of E-cadherin in endometrial cancer cells is associated with adverse prognostic features. This study aimed to evaluate the prognostic significance of decreased E-cadherin expression in patients with endornetrial cancer. Experimental Design: Between 1992 and 1999, 102 endometrial cancer patients with stage I-III disease underwent primary surgery at the University of Chicago. Representative tissue specimens were immunostained with a monoclonal antibody to E-cadherin. A semiquantitative evaluation scale was developed based on the percentage of endometrial cancer cells with membranous E-cadherin staining. Tissue sections were scored as {"}3{"} if >75{\%}, {"}2{"} if 25-75{\%}, {"}1{"} if 5-25{\%}, and {"}0{"} if <5{\%} of cells stained. E-Cadherin staining was correlated with overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and extrapelvic progression. Multivariate Cox proportional hazards modeling was used to estimate hazard ratios, controlling for clinicopathological characteristics and adjuvant treatment. Median follow-up for the study group was 58.5 months. Results: E-Cadherin staining was scored as 0, 1, 2, and 3 in 29.4{\%}, 18.6{\%}, 26.5{\%}, 25.5{\%} of cases, respectively. E-Cadherin expression was positively correlated with myometrial invasion (Kendall τ: 0.30, P < 0.01), and negatively correlated with grade (Kendall τ: -0.13, P = 0.15) and papillary serous or clear cell histology (Kendall τ: -0.14, P = 0.12). Five-year actuarial OS, CSS, PFS, and extrapelvic recurrence rates for negative (score = 0), heterogeneous (score = 1-2), and positive (score = 3) staining were as follows: OS, 69.2 versus 75.7 versus 81.0{\%} (P = 0.64); CSS, 78.8 versus 91.2 versus 95.5{\%} (P = 0.19); PFS, 69.1 versus 88.6 versus 92.2{\%} (P = 0.079), and extrapelvic progression, 20.8 versus 7.3 versus 4.0{\%} (P = 0.17). On multivarlate Cox regression, a higher E-cadherin expression score was associated With decreased overall mortality [hazard ratio (HR), 0.59; 95{\%} confidence interval (CI), 0.34-1.03; P = 0.066), and statistically significant decreases in endometrial cancer mortality (HR, 0.23; 95{\%} CI, 0.055-0.94; P = 0.040), disease progression (HR, 0.28; 95{\%} CI, 0.10-0.77; P = 0.014), and extrapelvic recurrence (HR, 0.24; 95{\%} CI, 0.062-0.97; P = 0.045). Conclusions: Decreased E-cadherin expression is an independent prognostic factor for disease progression and mortality in pathological stage I-III endometrial cancer. Evaluation of E-cadherin expression may aid in the selection of patients for more aggressive adjuvant therapy.",
author = "Mell, {Loren K.} and Jeffrey Meyer and Maria Tretiakova and Andrey Khramtsov and Can Gong and Yamada, {S. Diane} and Montag, {Anthony G.} and Mundt, {Arno J.}",
year = "2004",
month = "8",
day = "15",
doi = "10.1158/1078-0432.CCR-0943-03",
language = "English (US)",
volume = "10",
pages = "5546--5553",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "16",

}

TY - JOUR

T1 - Prognostic significance of E-cadherin protein expression in pathological stage I-III endometrial cancer

AU - Mell, Loren K.

AU - Meyer, Jeffrey

AU - Tretiakova, Maria

AU - Khramtsov, Andrey

AU - Gong, Can

AU - Yamada, S. Diane

AU - Montag, Anthony G.

AU - Mundt, Arno J.

PY - 2004/8/15

Y1 - 2004/8/15

N2 - Purpose: Decreased expression of E-cadherin in endometrial cancer cells is associated with adverse prognostic features. This study aimed to evaluate the prognostic significance of decreased E-cadherin expression in patients with endornetrial cancer. Experimental Design: Between 1992 and 1999, 102 endometrial cancer patients with stage I-III disease underwent primary surgery at the University of Chicago. Representative tissue specimens were immunostained with a monoclonal antibody to E-cadherin. A semiquantitative evaluation scale was developed based on the percentage of endometrial cancer cells with membranous E-cadherin staining. Tissue sections were scored as "3" if >75%, "2" if 25-75%, "1" if 5-25%, and "0" if <5% of cells stained. E-Cadherin staining was correlated with overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and extrapelvic progression. Multivariate Cox proportional hazards modeling was used to estimate hazard ratios, controlling for clinicopathological characteristics and adjuvant treatment. Median follow-up for the study group was 58.5 months. Results: E-Cadherin staining was scored as 0, 1, 2, and 3 in 29.4%, 18.6%, 26.5%, 25.5% of cases, respectively. E-Cadherin expression was positively correlated with myometrial invasion (Kendall τ: 0.30, P < 0.01), and negatively correlated with grade (Kendall τ: -0.13, P = 0.15) and papillary serous or clear cell histology (Kendall τ: -0.14, P = 0.12). Five-year actuarial OS, CSS, PFS, and extrapelvic recurrence rates for negative (score = 0), heterogeneous (score = 1-2), and positive (score = 3) staining were as follows: OS, 69.2 versus 75.7 versus 81.0% (P = 0.64); CSS, 78.8 versus 91.2 versus 95.5% (P = 0.19); PFS, 69.1 versus 88.6 versus 92.2% (P = 0.079), and extrapelvic progression, 20.8 versus 7.3 versus 4.0% (P = 0.17). On multivarlate Cox regression, a higher E-cadherin expression score was associated With decreased overall mortality [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.34-1.03; P = 0.066), and statistically significant decreases in endometrial cancer mortality (HR, 0.23; 95% CI, 0.055-0.94; P = 0.040), disease progression (HR, 0.28; 95% CI, 0.10-0.77; P = 0.014), and extrapelvic recurrence (HR, 0.24; 95% CI, 0.062-0.97; P = 0.045). Conclusions: Decreased E-cadherin expression is an independent prognostic factor for disease progression and mortality in pathological stage I-III endometrial cancer. Evaluation of E-cadherin expression may aid in the selection of patients for more aggressive adjuvant therapy.

AB - Purpose: Decreased expression of E-cadherin in endometrial cancer cells is associated with adverse prognostic features. This study aimed to evaluate the prognostic significance of decreased E-cadherin expression in patients with endornetrial cancer. Experimental Design: Between 1992 and 1999, 102 endometrial cancer patients with stage I-III disease underwent primary surgery at the University of Chicago. Representative tissue specimens were immunostained with a monoclonal antibody to E-cadherin. A semiquantitative evaluation scale was developed based on the percentage of endometrial cancer cells with membranous E-cadherin staining. Tissue sections were scored as "3" if >75%, "2" if 25-75%, "1" if 5-25%, and "0" if <5% of cells stained. E-Cadherin staining was correlated with overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and extrapelvic progression. Multivariate Cox proportional hazards modeling was used to estimate hazard ratios, controlling for clinicopathological characteristics and adjuvant treatment. Median follow-up for the study group was 58.5 months. Results: E-Cadherin staining was scored as 0, 1, 2, and 3 in 29.4%, 18.6%, 26.5%, 25.5% of cases, respectively. E-Cadherin expression was positively correlated with myometrial invasion (Kendall τ: 0.30, P < 0.01), and negatively correlated with grade (Kendall τ: -0.13, P = 0.15) and papillary serous or clear cell histology (Kendall τ: -0.14, P = 0.12). Five-year actuarial OS, CSS, PFS, and extrapelvic recurrence rates for negative (score = 0), heterogeneous (score = 1-2), and positive (score = 3) staining were as follows: OS, 69.2 versus 75.7 versus 81.0% (P = 0.64); CSS, 78.8 versus 91.2 versus 95.5% (P = 0.19); PFS, 69.1 versus 88.6 versus 92.2% (P = 0.079), and extrapelvic progression, 20.8 versus 7.3 versus 4.0% (P = 0.17). On multivarlate Cox regression, a higher E-cadherin expression score was associated With decreased overall mortality [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.34-1.03; P = 0.066), and statistically significant decreases in endometrial cancer mortality (HR, 0.23; 95% CI, 0.055-0.94; P = 0.040), disease progression (HR, 0.28; 95% CI, 0.10-0.77; P = 0.014), and extrapelvic recurrence (HR, 0.24; 95% CI, 0.062-0.97; P = 0.045). Conclusions: Decreased E-cadherin expression is an independent prognostic factor for disease progression and mortality in pathological stage I-III endometrial cancer. Evaluation of E-cadherin expression may aid in the selection of patients for more aggressive adjuvant therapy.

UR - http://www.scopus.com/inward/record.url?scp=4143051355&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4143051355&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-0943-03

DO - 10.1158/1078-0432.CCR-0943-03

M3 - Article

C2 - 15328195

AN - SCOPUS:4143051355

VL - 10

SP - 5546

EP - 5553

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 16

ER -