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Expression of Thyroid Transcription
Factor-1 (TTF-1) in Endometrial
Carcinoma
Prof. Jaudah Al-Maghrabi, MD, MSc, FRCPC, FCAP
Nisrin Anfinan, Khalid Sait, Hesham Sait, Mahmou Al-Ahwal,
Abdullah Basalamah.
1
Introduction
 Thyroid transcription factor-1 (TTF-1) is DNAbinding
protein that is encoded by a gene located on
chromosome 14q13.
 TTF-1 regulates transcription of genes specific for
the thyroid and lung and selectively expressed in these
organs.
 In anatomic pathology, it is used as a marker to
determine if a tumor arises from the lung or thyroid, to
distinguish between primary and secondary carcinomas.
2
Lung adenocarcinoma Thyroid papillary carcinoma
Introduction
 Some studies showed that TTF-1 also can be
expressed in extrapulmonary & extrathyroid
adenocarcinomas.
 The data on TTF-1 expression in endometrial
cancer is limited and conflicting (range: 1-26%)
4
Aim
 The aim of this study is to evaluate the
immunoexpression of TTF-1 in primary
endometrial adenocarcinoma.
5
Material and methods
 A total of 116 endometrial carcinomas were retrieved
from Department of Pathology, KAUH.
 The categories of endometrial adenocarcinoma
include:
 78 grade I endometrioid
 17 grade II endometrioid
 12 grade III endometrioid
 7 serous
 2 clear cell.
 Tissue microarray (TMA) was prepared
6
Tissue Array
9
Tissue Array
10
Tissue Array
11
12
Material and methods
 Tissue sections were immunostained using monoclonal
antibodies to TTF-1 clones 8G7G3/1 (dilution 1:100, Dako)
 The immunohistochemical stains were scored
semiquantitativly from 0 to 5+.
13
14
Tissue Array
Results
 TTF-1 immunoexpression was detected only in 2
carcinomas (1 serous and one endometrioid type)
and in both cases the staining score was 1+.
16
17
18
19
Discussion
 Bejarano et al, Mod Pathol 1996; 9(4):445-452.
TTF-1 has been reported in 1 of 8 endometrial adenocarcinomas.
 At M. D. Anderson, Deavers et al. Arch Pathol Lab Med
2008; 132(2):175-180.
 Studied TTF-1 expression in 31 endometrial endometrioid
adenocarcinomas (11 grade I, 8 grade II, and 12 grade III).
 TTF-1, immunoreactivity was identified in 5 cases (16%), and
ranged from focal to diffuse in distribution.
 There was no correlation between TTF-1 expression and the
degree of differentiation,
20
Discussion
 Zhang et al. (Int J Gynecol Pathol 2012; 28(1):10-18).
• TTF-1 positivity was identified in 26% (SPT24/Vision)
• TTF-1 positivity was identified in 1%-6.4%. 8G7G3/1/Dako
• TTF-1 is frequently detected in uterine malignant mixed
Mullerian tumor (82%), more common in uterine
tumors than ovarian tumors.
 Turner et al. Arch Pathol Lab Med 2012; 136(2):163-171.
TTF-1 positivity was identified in 1 out of 48 endometrial
adenocarcinoma.
21
Discussion
 Ervine et al. Histopathology. 2014 May;64(6):840-6.
Demonstrated that TTF-1 is expressed in a small subset of
all categories of endometrial adenocarcinoma as follows:
 2% low grade endometrioid
 11% grade 3 endometrioid
 9% serous
 7% clear cell
 they showed that TTF-1 positivity in low grade
endometrioid adenocarcinomas is a poor prognostic factor.
22
Number of
cases
Technique Positivity
(%)
Bejarano et al, 1996 8 Conventional 12
Deavers et al, 2 008 31 Conventional 16
Zhang et al, 2012 58 TMA 1-6.4
Turner et al, 2012 48 TMA 2
Ervine et al, 2014 331 TMA 2-11
Al-Maghrabi et al, 2014 116 TMA 1.7
23
Conclusion
 Our study confirms that TTF-1 is expressed in a
small proportion of endometrial
adenocarcinomas
 In patient with TTF-1 immunoexpression,
endometrial carcinomas should be considered
when evaluating patients with adenocarcinoma
of unknown origin.
24
Conclusion
 TTF-1 immunostaining has the potential to
misguide the pathologists, So care should be
exercised in its interpretation, for example, in
cases where there is a lung lesion in a patient with
a background of a gynaecological malignancy.
 TTF-1 positivity cannot be used as an indicator of
poorer prognosis in endometrial carcinoma.
25
Acknowledgment
This study was supported by a grant from the
Scientific Chair of Prof. Abdullah Hussain,
Basalamah for Gynecological Cancer.
King, Abdulaziz University, Jeddah, Saudi
Arabia
26
Thanks

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Tma ttf-2

  • 1. Expression of Thyroid Transcription Factor-1 (TTF-1) in Endometrial Carcinoma Prof. Jaudah Al-Maghrabi, MD, MSc, FRCPC, FCAP Nisrin Anfinan, Khalid Sait, Hesham Sait, Mahmou Al-Ahwal, Abdullah Basalamah. 1
  • 2. Introduction  Thyroid transcription factor-1 (TTF-1) is DNAbinding protein that is encoded by a gene located on chromosome 14q13.  TTF-1 regulates transcription of genes specific for the thyroid and lung and selectively expressed in these organs.  In anatomic pathology, it is used as a marker to determine if a tumor arises from the lung or thyroid, to distinguish between primary and secondary carcinomas. 2
  • 3. Lung adenocarcinoma Thyroid papillary carcinoma
  • 4. Introduction  Some studies showed that TTF-1 also can be expressed in extrapulmonary & extrathyroid adenocarcinomas.  The data on TTF-1 expression in endometrial cancer is limited and conflicting (range: 1-26%) 4
  • 5. Aim  The aim of this study is to evaluate the immunoexpression of TTF-1 in primary endometrial adenocarcinoma. 5
  • 6. Material and methods  A total of 116 endometrial carcinomas were retrieved from Department of Pathology, KAUH.  The categories of endometrial adenocarcinoma include:  78 grade I endometrioid  17 grade II endometrioid  12 grade III endometrioid  7 serous  2 clear cell.  Tissue microarray (TMA) was prepared 6
  • 8.
  • 11. 11
  • 12. 12
  • 13. Material and methods  Tissue sections were immunostained using monoclonal antibodies to TTF-1 clones 8G7G3/1 (dilution 1:100, Dako)  The immunohistochemical stains were scored semiquantitativly from 0 to 5+. 13
  • 14. 14
  • 16. Results  TTF-1 immunoexpression was detected only in 2 carcinomas (1 serous and one endometrioid type) and in both cases the staining score was 1+. 16
  • 17. 17
  • 18. 18
  • 19. 19
  • 20. Discussion  Bejarano et al, Mod Pathol 1996; 9(4):445-452. TTF-1 has been reported in 1 of 8 endometrial adenocarcinomas.  At M. D. Anderson, Deavers et al. Arch Pathol Lab Med 2008; 132(2):175-180.  Studied TTF-1 expression in 31 endometrial endometrioid adenocarcinomas (11 grade I, 8 grade II, and 12 grade III).  TTF-1, immunoreactivity was identified in 5 cases (16%), and ranged from focal to diffuse in distribution.  There was no correlation between TTF-1 expression and the degree of differentiation, 20
  • 21. Discussion  Zhang et al. (Int J Gynecol Pathol 2012; 28(1):10-18). • TTF-1 positivity was identified in 26% (SPT24/Vision) • TTF-1 positivity was identified in 1%-6.4%. 8G7G3/1/Dako • TTF-1 is frequently detected in uterine malignant mixed Mullerian tumor (82%), more common in uterine tumors than ovarian tumors.  Turner et al. Arch Pathol Lab Med 2012; 136(2):163-171. TTF-1 positivity was identified in 1 out of 48 endometrial adenocarcinoma. 21
  • 22. Discussion  Ervine et al. Histopathology. 2014 May;64(6):840-6. Demonstrated that TTF-1 is expressed in a small subset of all categories of endometrial adenocarcinoma as follows:  2% low grade endometrioid  11% grade 3 endometrioid  9% serous  7% clear cell  they showed that TTF-1 positivity in low grade endometrioid adenocarcinomas is a poor prognostic factor. 22
  • 23. Number of cases Technique Positivity (%) Bejarano et al, 1996 8 Conventional 12 Deavers et al, 2 008 31 Conventional 16 Zhang et al, 2012 58 TMA 1-6.4 Turner et al, 2012 48 TMA 2 Ervine et al, 2014 331 TMA 2-11 Al-Maghrabi et al, 2014 116 TMA 1.7 23
  • 24. Conclusion  Our study confirms that TTF-1 is expressed in a small proportion of endometrial adenocarcinomas  In patient with TTF-1 immunoexpression, endometrial carcinomas should be considered when evaluating patients with adenocarcinoma of unknown origin. 24
  • 25. Conclusion  TTF-1 immunostaining has the potential to misguide the pathologists, So care should be exercised in its interpretation, for example, in cases where there is a lung lesion in a patient with a background of a gynaecological malignancy.  TTF-1 positivity cannot be used as an indicator of poorer prognosis in endometrial carcinoma. 25
  • 26. Acknowledgment This study was supported by a grant from the Scientific Chair of Prof. Abdullah Hussain, Basalamah for Gynecological Cancer. King, Abdulaziz University, Jeddah, Saudi Arabia 26