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01-02-2010 | Original Article

Comparing the scoring mechanisms of p16^INK4a immunohistochemistry based on independent nucleic stains and independent cytoplasmic stains in distinguishing between endocervical and endometrial adenocarcinomas in a tissue microarray study

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

Published in: Archives of Gynecology and Obstetrics | Issue 2/2010

Abstract

Background

Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect the uterus; however, their biological behaviors are quite different. This distinction has clinical significance because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate two different scoring mechanisms of p16^INK4a immunohistochemical (IHC) stain in distinguishing between primary ECAs and EMAs.

Methods

A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 ECAs and 21 EMAs. Tissue array sections were stained with a commercially available antibody, p16^INK4a. The avidin–biotin complex method was used to visualize antigens. The staining intensity and extent of the IHC reactions were evaluated using a semi-quantitative scoring system. Two scoring methods were defined on the following bases: (1) independent cytoplasmic staining alone, irrespective of nucleic stain (Method C) and (2) independent nucleic staining alone, irrespective of cytoplasmic staining. (Method N).

Results

Of the two scoring mechanisms for p16^INK4a expression, Method N showed a significant difference (P = 0.015), but Method C showed no significant (P = 0.432) frequency differences in distinguishing between ECAs and EMAs. However, Method N had a higher overall accuracy rate (71.4%) in accurately diagnosing ECAs from EMAs in the total number of p16^INK4a IHC cases.

Conclusion

According to the data of p16^INK4a expression in this TMA study, Method N is favorable and efficient in distinguishing between ECAs and EMAs, while Method C is not.

Lurain JR (2007) Uterine cancer, chap 33. In: Berek JS (ed) Berek & Novak’s gynecology, 14th edn. Lippincott Williams & Wilkins, Philadelphia USA, pp 1343–1402

Bidus MA, Elkas JC (2007) Cervical and vaginal cancer, chap 34. In: Berek JS (ed) Berek & Novak’s gynecology, 14th edn. Lippincott Williams & Wilkins, Philadelphia USA, pp 1343–1402

Zaino RJ (2002) The fruits of our labors: Distinguishing endometrial from endocervical adenocarcinoma. Int J Gynecol Pathol 24:1–3CrossRef

Castrillon DH, Lee KR, Nucci MR (2002) Distinction between endometrial and endocervical adenocarcinoma: An immunohistochemical study. Int J Gynecol Pathol 24:4–10CrossRef

McCluggage WG, Sumathi P, McBride HA, Patterson A (2002) A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids in the distinction between primary endometrial and endocervical adenocarcinomas. Int J Gynecol Pathol 24:11–15CrossRef

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

Miller RT (2002) Endocervical vs. endometrial adenocarcinoma. The Focus—Immunohistochemistry, Jan; 1–2

Miller RT (2003) Endocervical vs. endometrial adenocarcinoma: update on useful immunohistochemical markers. The Focus—Immunohistochemistry, Apr; 1–2

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

10.

Khoury T, Tan D, Wang J, Intengan M, Yang J, Alrawi S et al (2006) Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma. BMC Clin Pathol 6:1–9CrossRefPubMed

11.

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

12.

Cheng YW, Wu MF, Wang J, Yeh KT, Goan YG, Chiou HL et al (2007) Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation. Cancer Res 67:10686–10693CrossRefPubMed

13.

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

14.

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

15.

Han CP, Lee MY, Tzeng SL, Yao CC, Wang PH, Cheng YW et al (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

16.

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

17.

Milde-Langosch K, Ocon E, Becker G, Löning T (1998) p16/MTS1 inactivation in ovarian carcinomas: high frequency of reduced protein expression associated with hypermethylation or mutation in endometrioid and mucinous tumors. Int J Cancer 79:61–65CrossRefPubMed

18.

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

19.

Musgrove EA, Lee CSL, Cornish AL, Swarbrick A, Sutherland RL (1997) Antiprogestin inhibition of cell cycle progression in T47-D breast cancer cells is accompanied by induction of the cyclin-dependent kinase inhibitor p24. Mol Endocrinol 11:54–66CrossRefPubMed

20.

Milde-Langosch K, Riethdorf L, Bamberger A-M, Löning T (1999) P16/MTS1 and pRb expression in endometrial carcinomas. Virchows Arch 434:23–28CrossRefPubMed

21.

Vallmanya Llena FR, Laborda Rodríguez A, Lloreta Trull J, Cortadellas Angel R, Placer Santos J, Mas Gelabert A (2006) Immunohistochemical expression of p53, p24, p16, and cyclin D1 in superficial bladder cancer. A tissue microarray study. Actas Urol Esp 30:754–762PubMedCrossRef

22.

Blokx WA, de Jong EM, de Wilde PC, Bulten J, Link MM, Ruiter DJ et al (2003) P16 and p53 expression in (pre)malignant epidermal tumors of renal transplant recipients and immunocompetent individuals. Mod Pathol 16:869–878CrossRefPubMed

23.

Huang HY, Huang WW, Lin CN, Eng HL, Li SL, Li CF et al (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 13:1633–1644CrossRefPubMed

24.

Kommoss S, Du Bois A, Ridder R, Trunk MJ, Schmidt D, Pfisterer J et al (2007) Independent prognostic significance of cell cycle regulator proteins p16INK4a 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 96:306–313CrossRefPubMed

25.

Camp RL, Chung GG, Rimm DL (2002) Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med 8:1323–1327CrossRefPubMed

26.

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

27.

Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P et al (2005) PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 23:5357–5364CrossRefPubMed

28.

Powell EL, Leoni LM, Canto MI et al (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 29:1497–1504CrossRefPubMed

29.

Ranade K, Hussussian CJ, Sikorski RS, Varmus HE, Goldstein AM, Tucker MA et al (1995) Mutations associated with familial melanoma impair p16INK4 function. Nat Genet 10:114–116CrossRefPubMed

30.

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 29:52–68CrossRefPubMed

31.

Franquemont DW (1995) Differentiation and risk assessment of gastrointestinal stromal tumors. Am J Clin Pathol 103:41–47PubMed

32.

Borden EC, Baker LH, Bell RS et al (2003) Soft tissue sarcomas of adults: state of the translational science. Clin Cancer Res 9:1941–1956PubMed

33.

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 67:61–70CrossRefPubMed

34.

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 Jan 20. [Epub ahead of print]

35.

Han CP, Lee MY, Kok LF, Ruan A, Wu TS, Cheng YW et al (2009) Additional 3-marker (ER/Vim/CEA) panel engenders no supplemental benefit in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray study, Int J Gynecol Pathol; in publication

Title: Comparing the scoring mechanisms of p16INK4a immunohistochemistry based on independent nucleic stains and independent cytoplasmic stains in distinguishing between endocervical and endometrial adenocarcinomas in a tissue microarray study
Authors: Lai-Fong Kok
Ming-Yung Lee
Yeu-Sheng Tyan
Tina S. Wu
Ya-Wen Cheng
Mei-Fen Kung
Po-Hui Wang
Chih-Ping Han
Publication date: 01-02-2010
Publisher: Springer-Verlag
Published in: Archives of Gynecology and Obstetrics / Issue 2/2010
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-009-1094-0

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Comparing the scoring mechanisms of p16^INK4a immunohistochemistry based on independent nucleic stains and independent cytoplasmic stains in distinguishing between endocervical and endometrial adenocarcinomas in a tissue microarray study

Abstract

Background

Methods

Results

Conclusion

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Abstract

Background

Methods

Results

Conclusion

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