Top

Published in:

01-05-2010 | Original Article

A reappraisal of three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR), and five-marker (ER/Vim/CEA/PR/p16^INK4a) panels in the diagnostic distinction between primary endocervical and endometrial adenocarcinomas in a tissue microarray study

Authors: Chih-Ping Han, Ming-Yung Lee, Lai-Fong Kok, Tina S. Wu, Ya-Wen Cheng, Po-Hui Wang, Chia-Herng Yue, Yeu-Sheng Tyan

Published in: Archives of Gynecology and Obstetrics | Issue 5/2010

Abstract

Background

The choice of appropriate therapeutic plans for primary endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) depend on the tumor’s site of origin. The purpose of this study was to compare the performances of the commonly used three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR) and five-marker (ER/Vim/CEA/PR/p16^INK4a) panels in distinguishing between primary ECA and EMA.

Methods

A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. Utilizing the avidin-biotin (ABC) technique, tissue array sections were immunostained with five commercially available antibodies (ER, Vim, CEA, PR and p16^INK4a) to evaluate the performances of their respective three-, four- and five-marker panels in distinguishing between primary ECA and EMA.

Results

ER, PR and Vim were more likely to be expressed in EMA, while CEA and p16^INK4a were frequently expressed in ECA. The three-marker (ER/Vim/CEA) panel exhibits the most favorable performance in the distinction between these two gynecologic malignancies (ECA vs. EMA).

Conclusion

According to our data, when histomorphological and clinical doubt exists as to the primary site of origin, we recommend that the conventional three-marker (ER/Vim/CEA) panel is sufficient, appropriate and useful in distinguishing between primary ECA and EMA, instead of the four-marker (ER/Vim/CEA/PR) and five-marker (ER/Vim/CEA/PR/p16^INK4a) panels. Ancillary PR and p16^INK4a add no supplementary value to the performance of the conventional three-marker (ER/Vim/CEA) panel.

Lurain JR, Bidus MA, Elkas JC (2007) Uterine cancer, cervical and vaginal cancer. In: Berek RS (ed) Novak’s gynecology, 14th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1343–1402

Schorge JO, Knowles LM, Lea JS (2004) Adenocarcinoma of the cervix. Curr Treat Options Oncol 5:119–127CrossRefPubMed

Yao CC, Kok LF, Lee MY, Wang PH, Wu TS, Tyan YS et al (2009) Ancillary p16^INK4a adds no meaningful value to the performance of ER/PR/Vim/CEA panel in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray study. Arch Gynecol Obstet. 20 January 2009 (Epub ahead of print)

Remmele W, Schicketanz KH (1993) Immunohistochemical determination of estrogen, progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Pathol Res Pract 189:862–866PubMed

Walker RA (2006) Quantification of immunohistochemistry: issues concerning methods, utility and semiquantitative assessment I. Histopathology 49:406–410CrossRefPubMed

Taylor CR, Levenson RM (2006) Quantification of immunohistochemistry: issues concerning methods, utility and semiquantitative assessment II. Histopathology 49:411–424CrossRefPubMed

Zweig MH, Campbell G (1993) Receiver-Operating Characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39:561–577PubMed

Metz CE (1978) Basic principles of ROC analysis. Semin Nucl Med 8:283–298CrossRefPubMed

Kamoi S, AlJuboury MI, Akin MR, Silverberg SG (2002) Immunohistochemical staining in the distinction between primary endometrial and endocervical adenocarcinomas: another viewpoint. Int J Gynecol Pathol 21:217–223CrossRefPubMed

10.

Khoury T, Tan D, Wang J, Intengan M, Yang J, Alrawi S, Yan P, Byrd JC (2006) Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma. BMC Clin Pathol 6:1CrossRefPubMed

11.

Han CP, Lee MY, Tzeng SL, Yao CC, Wang PH, Cheng YW, Chen SL, Wu TS, Tyan YS, Kok LF (2008) Nuclear Receptor Interaction Protein (NRIP) expression assay using human tissue microarray and immunohistochemistry technology confirming nuclear localization. J Exp Clin Cancer Res 27:25CrossRefPubMed

12.

Han CP, Kok LF, Wang PW, Wu TS, Cheng YW, Lee MY et al (2009) Scoring p16^INK4a immunohistochemistry based on independent nucleic staining alone can sufficiently distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study. Mod Path 22:797–806

13.

Koo CL, Kok LF, Lee MY, Wu TS, Cheng YW, Hsu JD, Ruan A, Chao KC, Han CP (2009) Scoring mechanisms of p16^INK4a immunohistochemistry based on either independent nucleic stain or mixed cytoplasmic with nucleic expression can significantly signal to distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study. J Transl Med 7:25CrossRefPubMed

14.

Liao CL, Lee MY, Tyan YS, Kok LF, Wu TS, Koo CL, Wang PH, Chao KC, Han CP (2009) Progesterone receptor does not improve the performance and test effectiveness of the conventional three-marker panel, consisting of estrogen receptor, vimentin and carcinoembryonic antigen in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray extension study. J Transl Med 7:37CrossRefPubMed

15.

Bodner G, Schocke MF, Rachbauer F, Seppi K, Peer S, Fierlinger A, Sununu T, Jaschke WR (2002) Differentiation of malignant and benign musculoskeletal tumors: combined color and power Doppler US and spectral wave analysis. Radiology 223:410–416CrossRefPubMed

16.

McCluggage WG, Sumathi VP, McBride HA, Patterson A (2002) A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids the distinction between primary endometrial and endocervical adenocarcinomas. Int J Gynecol Pathol 21:11–15CrossRefPubMed

17.

Wehling M (2008) Translational medicine: science or wishful thinking? J Transl Med 6:31CrossRefPubMed

18.

Dabbs DJ, Sturtz K, Zaino RJ (1996) Distinguishing endometrial from endocervical adenocarcinoma. Hum Pathol 27:172–177CrossRefPubMed

19.

Castrillon DH, Lee KR, Nucci MR (2002) Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study. Int J Gynecol Pathol 21:4–10CrossRefPubMed

20.

Alkushi A, Irving J, Hsu F, Dupuis B, Liu CL, Rijn M et al (2003) Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray. Virchows Arch 442:271–277PubMed

21.

Miller RT (2002) Endocervical vs. endometrial adenocarcinoma. THE FOCUS—Immunohistochemistry Jan:1–2

22.

Miller RT (2003) Endocervical vs. endometrial adenocarcinoma: update on useful immunohistochemical markers. THE FOCUS—Immunohistochemistry. Apr:1–2

23.

Reid-Nicholson M, Iyengar P, Hummer AJ, Linkov I, Asher M, Soslow RA (2006) Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis. Mod Pathol 19(8):1091–1100 (Epub 28 April 2006)PubMed

24.

McCluggage WG, Jenkins D (2003) p16 immunoreactivity may assist in the distinction between endometrial and endocervical adenocarcinoma. Int J Gynecol Pathol 22:231–235CrossRefPubMed

25.

Mittal K, Soslow R, McCluggage WG (2008) Application of immunohistochemistry to gynecologic pathology. Arch Pathol Lab Med 132:402–423PubMed

Title: A reappraisal of three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR), and five-marker (ER/Vim/CEA/PR/p16INK4a) panels in the diagnostic distinction between primary endocervical and endometrial adenocarcinomas in a tissue microarray study
Authors: Chih-Ping Han
Ming-Yung Lee
Lai-Fong Kok
Tina S. Wu
Ya-Wen Cheng
Po-Hui Wang
Chia-Herng Yue
Yeu-Sheng Tyan
Publication date: 01-05-2010
Publisher: Springer-Verlag
Published in: Archives of Gynecology and Obstetrics / Issue 5/2010
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-009-1151-8

At a glance: The STEP trials

Springer Medicine

A reappraisal of three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR), and five-marker (ER/Vim/CEA/PR/p16^INK4a) panels in the diagnostic distinction between primary endocervical and endometrial adenocarcinomas in a tissue microarray study

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2010

3D color Doppler of monoamniotic twin cord entanglement

Computed tomographic angiography in diagnosis and management of placental polyp with neovascularization

Cotyledonoid leiomyoma and non-descent vaginal hysterectomy

Excision of high vaginal septum

Altered gene profile of placenta from women with intrahepatic cholestasis of pregnancy

A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate