ORIGINAL ARTICLE
Serous versus high-grade endometrioid endometrial carcinoma: immunohistochemistry of RFP is not useful for differentiation
1
Department of Pathology, Hacettepe University, Ankara, Turkey
2
Department of Pathology, Ankara Atatürk Training and Research Hospital, Ankara, Turkey
3
Department of Biostatistics, Hacettepe University, Ankara, Turkey
4
Department of Pathology, Etlik Zübeyde Hanim Research and Teaching Hospital, Ankara, Turkey
5
Department of Pathology, Bas‚kent University, Ankara, Turkey
Submission date: 2015-12-22
Final revision date: 2016-04-06
Acceptance date: 2016-04-11
Publication date: 2016-11-25
Pol J Pathol 2016;67(3):221-227
KEYWORDS
TOPICS
ABSTRACT
We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium.
A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher’s exact tests were performed for statistical analyses.
The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001).
Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.
A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher’s exact tests were performed for statistical analyses.
The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001).
Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.
REFERENCES (22)
1.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63: 11-30.
2.
Silverberg SG, Mutter GL, Kurman RJ, et al. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. In: World Health Organization Classification of Tumours. Tavassoli FA, Devilee P. (eds). IARC Press, Lyon 2003; 217-232.
3.
Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15: 10-17.
4.
Lax SF. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch 2004; 444: 213-223.
5.
Wright JD, Barrena Medel NI, Sehouli J, et al. Contemporary management of endometrial cancer. Lancet 2012; 379: 1352-1360.
6.
Creasman WT, Kohler MF, Odicino F, et al. Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium. Gynecol Oncol 2004; 95: 593-596.
7.
Halperin R, Zehavi S, Langer R, et al. Uterine papillary serous carcinoma (pure and mixed type) compared with moderately and poorly differentiated endometrioid carcinoma. A clinicopathologic study. Eur J Gynaecol Oncol 2002; 23: 300-304.
8.
McConechy MK, Ding J, Cheang MC, et al. Use of mutation profiles to refine the classification of endometrial carcinomas. J Pathol 2012; 228: 20-30.
9.
Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497: 67-73.
10.
Gilks CB, Oliva E, Soslow RA. Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma. Am J Surg Pathol 2013; 37: 874-881.
11.
Han G, Sidhu D, Duggan MA, et al. Reproducibility of histological cell type in high-grade endometrial carcinoma. Mod Pathol 2013; 26: 1594-1604.
12.
Clarke BA, Gilks CB. Endometrial carcinoma: controversies in histopathological assessment of grade and tumour cell type. J Clin Pathol 2010; 63: 410-415.
13.
Takahashi M, Inaguma Y, Hiai H, et al. Developmentally regulated expression of a human „finger”-containing gene encoded by the 5’ half of the ret transforming gene. Mol Cell Biol 1988; 8: 1853-1856.
14.
Tezel GG, Ordulu Z, Himmetoglu C, et al. The selective expression of ret finger protein in endometrial cancer: can RFP be a marker of serous carcinomas? Turk Patoloji Derg 2012; 28: 213-219.
15.
Tsukamoto H, Kato T, Enomoto A, et al. Expression of Ret finger protein correlates with outcomes in endometrial cancer. Cancer Sci 2009; 100: 1895-1901.
16.
Tezel G, Nagasaka T, Iwahashi N, et al. Different nuclear/cytoplasmic distributions of RET finger protein in different cell types. Pathol Int 1999; 49: 881-886.
17.
Soslow RA. High-grade endometrial carcinomas – strategies for typing. Histopathology 2013; 62: 89-110.
18.
Matalka I, Obeidat B, Mohtaseb A, et al. The significance of Wilms Tumor Gene (WT1) and p53 expression in curettage specimens of patients with endometrial carcinomas. Pathol Res Pract 2013; 209: 19-23.
19.
Chiang S, Soslow RA. Updates in diagnostic immunohistochemistry in endometrial carcinoma. Semin Diagn Pathol 2014; 31: 205-215.
20.
Hedley C, Sriraksa R, Showeil R, et al. The frequency and significance of WT-1 expression in serous endometrial carcinoma. Hum Pathol 2014; 45: 1879-1884.
21.
Hoang LN, McConechy MK, Köbel M, et al. Histotype-genotype correlation in 36 high-grade endometrial carcinomas. Am J Surg Pathol 2013; 37: 1421-1432.
22.
Bąkiewicz A, Michalak J, Sporny S. Immunoexpression and clinical significance of the PTEN and MLH1 proteins in endometrial carcinomas. Pol J Pathol 2010; 61: 185-191.
Share
RELATED ARTICLE
| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
