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Differential Diagnosis between Primary Endocervical and Endometrial Adenocarcinoma using Immunohistochemical Staining of Estrogen Receptor, Vimentin, Carcinoembryonic Antigen and p16

Marut Yanaranop MD*,***, Sucha Ayuwat MD*, Saranyu Nakrangsee MD**,***

Affiliation : * Department of Obstetrics and Gynecology, Rajavithi Hospital, Bangkok, Thailand ** Department of Pathology, Rajavithi Hospital, Bangkok, Thailand *** College of Medicine, Rangsit University, Bangkok, Thailand

Background : When clinical and histopathological evaluation is not effective in discriminating primary endocervical adenocarcinoma (ECAs) and endometrial adenocarcinoma (EMAs), an immunohistochemistry (IHC) method is regularly used in practice, which involves staining of estrogen receptor (ER), vimentin (Vim), monoclonal carcinoembryonic antigen (mCEA) and p16.
Objective : To evaluate the performance of IHC markers, ER, Vim, mCEA and p16, in differentiating between primary ECAs and EMAs and to compare the performances of two-, three- and four-marker panels. Material and Method: Women with cervical or uterine cancers who were diagnosed with mucinous or endometrioid adenocarcinoma or adenocarcinoma of non-otherwise specified, after cervical biopsy, endometrial biopsy or curettage, and who underwent elective surgery at Rajavithi Hospital between January 1, 2011 and June 30, 2012 were retrospectively reviewed. Paraffin-embedded tissue sections from pre-operative specimens were reviewed and stained with ER, Vim, mCEA and p16. Postoperative pathologic slides was reviewed and installed as the reference standard.
Results : Of 110 cases, 44 were primary ECAs and 66 were primary EMAs. ER and Vim were significantly expressed in EMAs (p<0.001), while mCEA and p16 were significantly expressed in ECAs (p<0.001). From multivariable analysis, Vim and p16 were the significant markers for differentiating ECAs and EMAs. A comparison of different combinations showed that panels of Vim/p16, ER/Vim/p16, Vim/mCEA/p16 and ER/Vim/mCEA/p16 achieved the highest overall accuracy of 97.9%.
Conclusion : Vim and p16 are the significant IHC markers and a two-marker panel of Vim/p16 is recommended for using in differentiating primary ECAs and EMAs; which a pattern of negative Vim and positive p16 expression favors diagnosis of ECAs while the converse pattern of positive Vim and negative p16 staining points to diagnosis of EMAs.

Keywords : Endocervical adenocarcinoma, Endometrial adenocarcinoma, Immuno-histochemistry, Estrogen receptor, Vimentin, Carcinoembryogenic antigen, p16


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