Tamoxifen-associated malignant endometrial tumors

Pathologic features and expression of hormone receptors estrogen-α, estrogen-β and progesterone; A case controlled study

James L. Wilder, Shahin Shajahan, Nada H. Khattar, Dawn M. Wilder, Jianming Yin, Rodney S. Rushing, Rick Beaven, Charlotte Kaetzel, Frederick R. Ueland, John R. Van Nagell, Richard J. Kryscio, Subodh M Lele

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Objective. Expression analysis of estrogen receptor-beta (ER-β) and estrogen receptor-alpha (ER-α) in tamoxifen-associated malignant endometrial tumors (TAMET) has not previously been published. Antiestrogens complexed with ER-β have been reported to result in activation of the activator protein-1 (AP-1) pathway that may result in cell proliferation and tumor growth. In this study, the pathologic features and expression of ER-α, ER-β and progesterone receptor (PR) in TAMET were determined and compared to matched cases of non-tamoxifen-associated endometrial cancers. Methods. TAMET (n = 33) were evaluated for pathologic features (tumor type, grade, depth of myometrial invasion, lymphvascular space invasion and lymph node status), expression of ER-α, ER-β and PR, and survival data (mean follow-up: 28.7 months). Each case was matched to two control patients with spontaneous endometrial cancers according to tumor type, grade and stage as well as patient age and weight (mean follow-up: 51.5 months). Formalin-fixed paraffin-embedded tissue sections were immunostained with anti-ER-α (1D5, Dako, Carpinteria, CA) and anti-PR (PgR636, Dako). Expression scores were determined as a sum of the product of staining intensity and proportion of cells staining (H-score). Deparaffinized sections of tumor were microdissected followed by RNA isolation. Quantification of ER-β mRNA was performed by real-time quantitative RT-PCR with results expressed as a percentage of β-actin mRNA. Results. Of the 33 cases 20 were endometrioid (8 grade 1, 10 grade 2, 2 grade 3), 9 papillary serous and 4 malignant mullerian mixed tumors. Using a multivariate conditional regression model, TAMET had lower ER-α expression (P = 0.018), higher PR expression (P = 0.029), and more frequent expression of ER-β (P = 0.032) as compared to control cases. Cases with TAMET had more deaths from cancer and significantly worse survival from disease than controls (P = 0.01 by a log rank test). Conclusion. TAMET are characterized by a lower expression of ER-α, higher expression of PR and more frequent expression of ER-β as compared to spontaneous tumors. Differential expression of ER-α and ER-β may alter the expression of key target genes (such as those induced by AP-1-dependent gene transcription), and contribute to the pathogenesis and clinical behavior of these tumors. Survival from disease was significantly worse for cases with TAMET as compared to controls.

Original languageEnglish (US)
Pages (from-to)553-558
Number of pages6
JournalGynecologic Oncology
Volume92
Issue number2
DOIs
StatePublished - Jan 1 2004

Fingerprint

Estrogen Receptor beta
Progesterone Receptors
Tamoxifen
Estrogen Receptors
Estrogens
Hormones
Neoplasms
Transcription Factor AP-1
Endometrial Neoplasms
Mullerian Mixed Tumor
Malignant Mixed Tumor
Staining and Labeling
Messenger RNA
Estrogen Receptor Modulators
Survival
Estrogen Receptor alpha
Paraffin
Formaldehyde
Genes

Keywords

  • Estrogen-α
  • Estrogen-β
  • Progesterone
  • TAMET
  • Tamoxifen-associated malignant endometrial tumors

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Tamoxifen-associated malignant endometrial tumors : Pathologic features and expression of hormone receptors estrogen-α, estrogen-β and progesterone; A case controlled study. / Wilder, James L.; Shajahan, Shahin; Khattar, Nada H.; Wilder, Dawn M.; Yin, Jianming; Rushing, Rodney S.; Beaven, Rick; Kaetzel, Charlotte; Ueland, Frederick R.; Van Nagell, John R.; Kryscio, Richard J.; Lele, Subodh M.

In: Gynecologic Oncology, Vol. 92, No. 2, 01.01.2004, p. 553-558.

Research output: Contribution to journalArticle

Wilder, JL, Shajahan, S, Khattar, NH, Wilder, DM, Yin, J, Rushing, RS, Beaven, R, Kaetzel, C, Ueland, FR, Van Nagell, JR, Kryscio, RJ & Lele, SM 2004, 'Tamoxifen-associated malignant endometrial tumors: Pathologic features and expression of hormone receptors estrogen-α, estrogen-β and progesterone; A case controlled study', Gynecologic Oncology, vol. 92, no. 2, pp. 553-558. https://doi.org/10.1016/j.ygyno.2003.10.040
Wilder, James L. ; Shajahan, Shahin ; Khattar, Nada H. ; Wilder, Dawn M. ; Yin, Jianming ; Rushing, Rodney S. ; Beaven, Rick ; Kaetzel, Charlotte ; Ueland, Frederick R. ; Van Nagell, John R. ; Kryscio, Richard J. ; Lele, Subodh M. / Tamoxifen-associated malignant endometrial tumors : Pathologic features and expression of hormone receptors estrogen-α, estrogen-β and progesterone; A case controlled study. In: Gynecologic Oncology. 2004 ; Vol. 92, No. 2. pp. 553-558.
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abstract = "Objective. Expression analysis of estrogen receptor-beta (ER-β) and estrogen receptor-alpha (ER-α) in tamoxifen-associated malignant endometrial tumors (TAMET) has not previously been published. Antiestrogens complexed with ER-β have been reported to result in activation of the activator protein-1 (AP-1) pathway that may result in cell proliferation and tumor growth. In this study, the pathologic features and expression of ER-α, ER-β and progesterone receptor (PR) in TAMET were determined and compared to matched cases of non-tamoxifen-associated endometrial cancers. Methods. TAMET (n = 33) were evaluated for pathologic features (tumor type, grade, depth of myometrial invasion, lymphvascular space invasion and lymph node status), expression of ER-α, ER-β and PR, and survival data (mean follow-up: 28.7 months). Each case was matched to two control patients with spontaneous endometrial cancers according to tumor type, grade and stage as well as patient age and weight (mean follow-up: 51.5 months). Formalin-fixed paraffin-embedded tissue sections were immunostained with anti-ER-α (1D5, Dako, Carpinteria, CA) and anti-PR (PgR636, Dako). Expression scores were determined as a sum of the product of staining intensity and proportion of cells staining (H-score). Deparaffinized sections of tumor were microdissected followed by RNA isolation. Quantification of ER-β mRNA was performed by real-time quantitative RT-PCR with results expressed as a percentage of β-actin mRNA. Results. Of the 33 cases 20 were endometrioid (8 grade 1, 10 grade 2, 2 grade 3), 9 papillary serous and 4 malignant mullerian mixed tumors. Using a multivariate conditional regression model, TAMET had lower ER-α expression (P = 0.018), higher PR expression (P = 0.029), and more frequent expression of ER-β (P = 0.032) as compared to control cases. Cases with TAMET had more deaths from cancer and significantly worse survival from disease than controls (P = 0.01 by a log rank test). Conclusion. TAMET are characterized by a lower expression of ER-α, higher expression of PR and more frequent expression of ER-β as compared to spontaneous tumors. Differential expression of ER-α and ER-β may alter the expression of key target genes (such as those induced by AP-1-dependent gene transcription), and contribute to the pathogenesis and clinical behavior of these tumors. Survival from disease was significantly worse for cases with TAMET as compared to controls.",
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T1 - Tamoxifen-associated malignant endometrial tumors

T2 - Pathologic features and expression of hormone receptors estrogen-α, estrogen-β and progesterone; A case controlled study

AU - Wilder, James L.

AU - Shajahan, Shahin

AU - Khattar, Nada H.

AU - Wilder, Dawn M.

AU - Yin, Jianming

AU - Rushing, Rodney S.

AU - Beaven, Rick

AU - Kaetzel, Charlotte

AU - Ueland, Frederick R.

AU - Van Nagell, John R.

AU - Kryscio, Richard J.

AU - Lele, Subodh M

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Objective. Expression analysis of estrogen receptor-beta (ER-β) and estrogen receptor-alpha (ER-α) in tamoxifen-associated malignant endometrial tumors (TAMET) has not previously been published. Antiestrogens complexed with ER-β have been reported to result in activation of the activator protein-1 (AP-1) pathway that may result in cell proliferation and tumor growth. In this study, the pathologic features and expression of ER-α, ER-β and progesterone receptor (PR) in TAMET were determined and compared to matched cases of non-tamoxifen-associated endometrial cancers. Methods. TAMET (n = 33) were evaluated for pathologic features (tumor type, grade, depth of myometrial invasion, lymphvascular space invasion and lymph node status), expression of ER-α, ER-β and PR, and survival data (mean follow-up: 28.7 months). Each case was matched to two control patients with spontaneous endometrial cancers according to tumor type, grade and stage as well as patient age and weight (mean follow-up: 51.5 months). Formalin-fixed paraffin-embedded tissue sections were immunostained with anti-ER-α (1D5, Dako, Carpinteria, CA) and anti-PR (PgR636, Dako). Expression scores were determined as a sum of the product of staining intensity and proportion of cells staining (H-score). Deparaffinized sections of tumor were microdissected followed by RNA isolation. Quantification of ER-β mRNA was performed by real-time quantitative RT-PCR with results expressed as a percentage of β-actin mRNA. Results. Of the 33 cases 20 were endometrioid (8 grade 1, 10 grade 2, 2 grade 3), 9 papillary serous and 4 malignant mullerian mixed tumors. Using a multivariate conditional regression model, TAMET had lower ER-α expression (P = 0.018), higher PR expression (P = 0.029), and more frequent expression of ER-β (P = 0.032) as compared to control cases. Cases with TAMET had more deaths from cancer and significantly worse survival from disease than controls (P = 0.01 by a log rank test). Conclusion. TAMET are characterized by a lower expression of ER-α, higher expression of PR and more frequent expression of ER-β as compared to spontaneous tumors. Differential expression of ER-α and ER-β may alter the expression of key target genes (such as those induced by AP-1-dependent gene transcription), and contribute to the pathogenesis and clinical behavior of these tumors. Survival from disease was significantly worse for cases with TAMET as compared to controls.

AB - Objective. Expression analysis of estrogen receptor-beta (ER-β) and estrogen receptor-alpha (ER-α) in tamoxifen-associated malignant endometrial tumors (TAMET) has not previously been published. Antiestrogens complexed with ER-β have been reported to result in activation of the activator protein-1 (AP-1) pathway that may result in cell proliferation and tumor growth. In this study, the pathologic features and expression of ER-α, ER-β and progesterone receptor (PR) in TAMET were determined and compared to matched cases of non-tamoxifen-associated endometrial cancers. Methods. TAMET (n = 33) were evaluated for pathologic features (tumor type, grade, depth of myometrial invasion, lymphvascular space invasion and lymph node status), expression of ER-α, ER-β and PR, and survival data (mean follow-up: 28.7 months). Each case was matched to two control patients with spontaneous endometrial cancers according to tumor type, grade and stage as well as patient age and weight (mean follow-up: 51.5 months). Formalin-fixed paraffin-embedded tissue sections were immunostained with anti-ER-α (1D5, Dako, Carpinteria, CA) and anti-PR (PgR636, Dako). Expression scores were determined as a sum of the product of staining intensity and proportion of cells staining (H-score). Deparaffinized sections of tumor were microdissected followed by RNA isolation. Quantification of ER-β mRNA was performed by real-time quantitative RT-PCR with results expressed as a percentage of β-actin mRNA. Results. Of the 33 cases 20 were endometrioid (8 grade 1, 10 grade 2, 2 grade 3), 9 papillary serous and 4 malignant mullerian mixed tumors. Using a multivariate conditional regression model, TAMET had lower ER-α expression (P = 0.018), higher PR expression (P = 0.029), and more frequent expression of ER-β (P = 0.032) as compared to control cases. Cases with TAMET had more deaths from cancer and significantly worse survival from disease than controls (P = 0.01 by a log rank test). Conclusion. TAMET are characterized by a lower expression of ER-α, higher expression of PR and more frequent expression of ER-β as compared to spontaneous tumors. Differential expression of ER-α and ER-β may alter the expression of key target genes (such as those induced by AP-1-dependent gene transcription), and contribute to the pathogenesis and clinical behavior of these tumors. Survival from disease was significantly worse for cases with TAMET as compared to controls.

KW - Estrogen-α

KW - Estrogen-β

KW - Progesterone

KW - TAMET

KW - Tamoxifen-associated malignant endometrial tumors

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