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.

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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.

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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%)

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Aim The aim of this study is to evaluate the

immunoexpression of TTF-1 in primary endometrial adenocarcinoma.

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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

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Tissue Array

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Tissue Array

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Tissue Array

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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+.

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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+.

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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,

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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.

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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.

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Number of cases

Technique Positivity (%)

Bejarano et al, 1996 8 Conventional 12Deavers et al, 2 008 31 Conventional 16 Zhang et al, 2012 58 TMA 1-6.4Turner et al, 2012 48 TMA 2Ervine et al, 2014 331 TMA 2-11Al-Maghrabi et al, 2014 116 TMA 1.7

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ConclusionOur 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.

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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.

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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

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Thanks