Skip to main content

Advertisement

Log in

Ancillary p16INK4a 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

  • Original Article
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) are uterine malignancies that have differing biological behavior. The choice of appropriate therapeutic plan depends indeed on the tumor’s site of origin. In this study, we not only compare the individual expression status of five immunomarkers (ER, PR, Vim, CEA, and p16INK4a), but also evaluate whether p16INK4a adds value to the ER/PR/Vim/CEA panel characteristics in distinguishing between primary ECA and EMA.

Methods

A tissue microarray (TMA) was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. TMA sections were immunostained with five anti-bodies, by avidin–biotin complex (ABC) method for antigen visualization. The staining intensity and area extent of the immunohistochemical (IHC) reactions were appraised by using the semi-quantitative scoring system.

Results

The four respective markers (ER, PR, Vim, CEA) and their combined panel expressions showed significant (p < 0.05) frequency differences between ECA and EMA tumors. The p16INK4a marker also revealed a significant frequency difference (p < 0.05) between the two sites of origin, but did not demonstrate to have any supplementary value to the 4-marker panel.

Conclusion

According to our data, when there is histomorphological and clinical doubt as to the primary site of origin, we recommend that the conventional 4-marker (ER/PR/Vim/CEA) panel is appropriate. Ancillary p16INK4a-marker testing does not add value to the 4-marker panel in distinguishing between primary ECA and EMA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Luran JR (2007) Uterine cancer. Gynecology, Chap. 33, 14th edn. Berek & Novak, Philadelphia, pp 1343–1402

  2. Bidus MA, Elkas JC (2007) Cervical and vagianl cancer. Gynecology, Chap. 34, 14th edn. Berek & Novak, Philadelphia, pp 1343–1402

  3. Dabbs DJ, Sturtz K, Zaino RJ (1996) Distinguishing endometrial from endocervical adenocarcinoma. Hum Pathol 27(2):172–177

    Article  PubMed  CAS  Google Scholar 

  4. Castrillon DH, Lee KR, Nucci MR (2002) Distinction between endometrial, endocervical adenocarcinoma: An immunohistochemical study. Int J Gynecol Pathol 21(1):4–10

    Article  PubMed  Google Scholar 

  5. McCluggage WG, Sumathi VP, McBride HA, Patterson AA (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(1):11–15

    Article  PubMed  Google Scholar 

  6. Alkushi A, Irving J, Hsu F, Dupuis B, Liu CL, Rijn M, Gilks CB (2003) Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray. Virchows Arch 442(3):271–277 [Epub 2003 Feb 12]

    PubMed  CAS  Google Scholar 

  7. Zweig MH, Campbell G (1993) Receiver-Operating Characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39(4):561–577

    PubMed  CAS  Google Scholar 

  8. Metz CE (1978) Basic principles of ROC analysis. Semin Nucl Med 8(4):283–298

    Article  PubMed  CAS  Google Scholar 

  9. 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(8):862–866

    PubMed  CAS  Google Scholar 

  10. Matos LL, Stabenow E, Tavares MR, Ferraz AR, Capelozzi VL, Pinhal MA (2006) Immunohistochemistry quantification by a digital computer-assisted method compared to semiquantitative analysis. Clinics 61(5):417–424

    Article  PubMed  Google Scholar 

  11. 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(3):217–223

    Article  PubMed  Google Scholar 

  12. 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 6:1

    Article  PubMed  CAS  Google Scholar 

  13. 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 27:25

    Article  PubMed  CAS  Google Scholar 

  14. Camp RL, Chung GG, Rimm DL (2002) Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med 8(11):1323–1327 [Epub 2002 Oct 21]

    Article  PubMed  CAS  Google Scholar 

  15. 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 2006 Apr 28]

    PubMed  CAS  Google Scholar 

  16. Cregger M, Berger AJ, Rimm DL (2006) Immunohistochemistry and quantitative analysis of protein expression. Arch Pathol Lab Med 130(7):1026–1030

    PubMed  CAS  Google Scholar 

  17. Revision B (2007) IHC nuclear image analysis user’s guide, MAN–0027, Jan 2007; Aperio, p 1–43. http://www.aperio.com/documents/XY_rel82/Aperio_IHC_Nuclear_Image_Analysis.pdf

  18. Fregonesi PA, Teresa DB, Duarte RA, Neto CB, de Oliveira MR, Soares CP (2003) p16(INK4A) immunohistochemical overexpression in premalignant and malignant oral lesions infected with human papillomavirus. J Histochem Cytochem 51(10):1291–1297

    PubMed  CAS  Google Scholar 

  19. Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, Shiraga S, Bainbridge T, Morich J, Heinrich MC (2005) PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 23(23):5357–5364 [Epub 2005 May 31]

    Article  PubMed  CAS  Google Scholar 

  20. Powell EL, Leoni LM, Canto MI, Forastiere AA, Iocobuzio-Donahue CA, Wang JS, Maitra A, Montgomery E (2005) Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications. Am J Surg Pathol 29(11):1497–1504

    Article  PubMed  Google Scholar 

  21. McCluggage WG, Jenkins D (2003) p16 immunoreactivity may assist in the distinction between endometrial and endocervical adenocarcinoma. Int J Gynecol Pathol 22(3):231–235

    Article  PubMed  CAS  Google Scholar 

  22. Vallmanya Llena FR, Laborda Rodríguez A, Lloreta Trull J, Cortadellas Angel R, Placer Santos J, Mas Gelabert A (2006) Immunohistochemical expression of p53, p21, p16, and cyclin D1 in superficial bladder cancer. A tissue microarray study. Actas Urol Esp 30(8):754–762

    Article  PubMed  CAS  Google Scholar 

  23. Milde-Langosch K, Bamberger AM, Rieck G, Kelp B, Löning T (2001) Overexpression of the p16 cell cycle inhibitor in breast cancer is associated with a more malignant phenotype. Breast Cancer Res Treat 67(1):61–70

    Article  PubMed  CAS  Google Scholar 

  24. Ranade K, Hussussian CJ, Sikorski RS, Varmus HE, Goldstein AM, Tucker MA, Serrano M, Hannon GJ, Beach D, Dracopoli NC (1995) Mutations associated with familial melanoma impair p16INK4 function. Nat Genet 10(1):114–116

    Article  PubMed  CAS  Google Scholar 

  25. Miettinen M, Sobin LH, Lasota J (2005) Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with longterm follow-up. Am J Surg Pathol 29(1):52–68

    Article  PubMed  Google Scholar 

  26. Huang HY, Huang WW, Lin CN, Eng HL, Li SH, Li CF, Lu D, Yu SC, Hsiung CY (2006) Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in gastrointestinal stromal tumors: prognostic implications and correlations with risk stratification of NIH consensus criteria. Ann Surg Oncol 13(12):1633–1644 [Epub 2006 Sep 30]

    Article  PubMed  Google Scholar 

  27. Kommoss S, du Bois A, Ridder R, Trunk MJ, Schmidt D, Pfisterer J, Kommoss F, the AGO-OVAR (2007) Independent prognostic significance of cell cycle regulator proteins p16(INK4a) and pRb in advanced-stage ovarian carcinoma including optimally debulked patients: a translational research subprotocol of a randomised study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group. Br J Cancer 96(2):306–313

    Google Scholar 

  28. Grayson W (2003) Mini-symposium: immunohistologyingynaecological pathology: application of immunohistochemistry in the evaluation of neoplastic epithelial lesions of the uterine cervix and endometrium. Curr Diagn Pathol 9:19–25. http://download.journals.elsevierhealth.com/pdfs/journals/0968-6053/PIIS0968605302901523.pdf

  29. Miller RT (2003) Endocervical vs. endometrial adenocarcinoma: update on useful immunohistochemical markers, The FOCUS—Immunohistochemistry, 1–2 Apr 2003. http://ihcworld.com/_newsletter/2003/focus_apr_2003.pdf

  30. Mittal K, Soslow R, McCluggage WG (2008) Application of immunohistochemistry to gynecologic pathology. Arch Pathol Lab Med 132(3):402–423

    Google Scholar 

Download references

Acknowledgments

This work was supported in parts by grants from Department of Health, (DOH98-PAB-1001-E and DOH98-PAB-1009-I), and Chung-Shan Medical University Hospital, Taiwan, ROC.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chih-Ping Han.

Additional information

C.-C. Yao and L.-F. Kok have equally contributed to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yao, CC., Kok, LF., Lee, MY. et al. Ancillary p16INK4a 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 280, 405–413 (2009). https://doi.org/10.1007/s00404-008-0859-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-008-0859-1

Keywords

Navigation