Advertisement

Virchows Archiv

, Volume 464, Issue 6, pp 673–679 | Cite as

HNF4A immunohistochemistry facilitates distinction between primary and metastatic breast and gastric carcinoma

  • R. S. van der PostEmail author
  • P. Bult
  • I. P. Vogelaar
  • M. J. L. Ligtenberg
  • N. Hoogerbrugge
  • J. H. van Krieken
Original Article

Abstract

The distinction between primary gastric adenocarcinoma and gastric metastatic breast carcinoma can be difficult. Expression of hepatocyte nuclear factor 4A (HNF4A) has been described as being specific to distinguish between neoplastic gastric and breast epithelial cells. The aim of this study was to validate the use of HNF4A with immunohistochemistry in discriminating gastric from breast carcinomas. Immunohistochemical expressions of HNF4A, estrogen receptor (ER), progesterone receptor (PR), and BRST-2 were determined in primary sporadic gastric adenocarcinomas (n = 107) and breast carcinomas (n = 105). The same markers and clinicopathological features were studied in 1 patient with breast metastasis of gastric cancer, 6 patients with gastric metastases of breast cancer, and 13 patients with both primary gastric and breast carcinomas. HNF4A expression was seen in 106 of 107 primary gastric adenocarcinomas and was absent in all 105 primary breast carcinomas (sensitivity 99 %, specificity 100 %). ER, PR, and BRST-2 were 100 % specific for breast carcinomas with sensitivities of 77, 58, and 38 %, respectively. The metastasis of gastric carcinoma to the breast showed strong expression of HNF4A. None of the metastases of breast carcinomas to the stomach showed expression of HNF4A. Tissues of patients with two primary carcinomas showed strong expression of HNF4A in all gastric carcinomas and no expression in breast carcinomas. Our results indicate that HNF4A is a very good marker to discriminate between primary and metastatic gastric and breast carcinomas.

Keywords

Immunohistochemistry HNF4A Gastric carcinoma Breast carcinoma 

Notes

Acknowledgments

The authors would like to thank Monique Link (technical assistance).

Conflict of interest

The authors have no competing interests.

References

  1. 1.
    Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, Chung DC, Norton J, Ragunath K, Van Krieken JH, Dwerryhouse S, Caldas C (2010) Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 47:436–444, 2010/07/02 edn. doi: 10.1136/jmg.2009.074237 PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Pharoah PD, Guilford P, Caldas C (2001) Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology 121:1348–1353, 2001/12/01 ednPubMedCrossRefGoogle Scholar
  3. 3.
    Benusiglio PR, Malka D, Rouleau E, De Pauw A, Buecher B, Nogues C, Fourme E, Colas C, Coulet F, Warcoin M, Grandjouan S, Sezeur A, Laurent-Puig P, Moliere D, Tlemsani C, Di Maria M, Byrde V, Delaloge S, Blayau M, Caron O (2013) CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study. J Med Genet 50:486–489, 2013/05/28 edn. doi: 10.1136/jmedgenet-2012-101472 PubMedCrossRefGoogle Scholar
  4. 4.
    Jakubowska A, Scott R, Menkiszak J, Gronwald J, Byrski T, Huzarski T, Gorski B, Cybulski C, Debniak T, Kowalska E, Starzynska T, Lawniczak M, Narod S, Lubinski J (2003) A high frequency of BRCA2 gene mutations in Polish families with ovarian and stomach cancer. Eur J Hum Genet 11:955–958, 2003/12/03 edn. doi: 10.1038/sj.ejhg.5201064 PubMedCrossRefGoogle Scholar
  5. 5.
    Friedenson B (2005) BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian. MedGenMed 7:60, 2005/12/22 ednPubMedCentralPubMedGoogle Scholar
  6. 6.
    Moran A, O’Hara C, Khan S, Shack L, Woodward E, Maher ER, Lalloo F, Evans DG (2012) Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam Cancer 11:235–242, 2011/12/22 edn. doi: 10.1007/s10689-011-9506-2 PubMedCrossRefGoogle Scholar
  7. 7.
    Graham WP 3rd (1964) Gastro-intestinal metastases from carcinoma of the breast. Ann Surg 159:477–480, 1964/03/01 ednPubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Choi SH, Sheehan FR, Pickren JW (1964) Metastatic involvement of the stomach by breast cancer. Cancer 17:791–797, 1964/06/01 ednPubMedCrossRefGoogle Scholar
  9. 9.
    Cifuentes N, Pickren JW (1979) Metastases from carcinoma of mammary gland: an autopsy study. J Surg Oncol 11:193–205, 1979/01/01 ednPubMedCrossRefGoogle Scholar
  10. 10.
    Reiman T, Butts CA (2001) Upper gastrointestinal bleeding as a metastatic manifestation of breast cancer: a case report and review of the literature. Can J Gastroenterol 15:67–71, 2001/03/16 ednPubMedGoogle Scholar
  11. 11.
    Almubarak MM, Lae M, Cacheux W, de Cremoux P, Pierga JY, Reyal F, Bennett SP, Falcou MC, Salmon RJ, Baranger B, Mariani P (2011) Gastric metastasis of breast cancer: a single centre retrospective study. Dig Liver Dis 43:823–827, 2011/05/28 edn. doi: 10.1016/j.dld.2011.04.009 PubMedCrossRefGoogle Scholar
  12. 12.
    BG Taal, FC den Hartog Jager, R Steinmetz and H Peterse (1992) The spectrum of gastrointestinal metastases of breast carcinoma: I. Stomach. Gastrointest Endosc, vol 38, 1992/03/01 edn.,Google Scholar
  13. 13.
    Sato T, Muto I, Fushiki M, Hasegawa M, Hasegawa M, Sakai T, Sekiya M (2008) Metastatic breast cancer from gastric and ovarian cancer, mimicking inflammatory breast cancer: report of two cases. Breast Cancer 15:315–320, 2008/03/04 edn. doi: 10.1007/s12282-008-0040-5 PubMedCrossRefGoogle Scholar
  14. 14.
    Hamby LS, McGrath PC, Cibull ML, Schwartz RW (1991) Gastric carcinoma metastatic to the breast. J Surg Oncol 48:117–121, 1991/10/01 ednPubMedCrossRefGoogle Scholar
  15. 15.
    Boutis AL, Andreadis C, Patakiouta F, Mouratidou D (2006) Gastric signet-ring adenocarcinoma presenting with breast metastasis. World J Gastroenterol 12:2958–2961, 2006/05/24 ednPubMedGoogle Scholar
  16. 16.
    Koyama T, Sekine S, Taniguchi H, Tsuda H, Ikegami M, Hano H, Kushima R (2011) Hepatocyte nuclear factor 4A expression discriminates gastric involvement by metastatic breast carcinomas from primary gastric adenocarcinomas. Hum Pathol 42:1777–1784, 2011/07/08 edn. doi: 10.1016/j.humpath.2011.04.002 PubMedCrossRefGoogle Scholar
  17. 17.
    Kojima K, Kishimoto T, Nagai Y, Tanizawa T, Nakatani Y, Miyazaki M, Ishikura H (2006) The expression of hepatocyte nuclear factor-4alpha, a developmental regulator of visceral endoderm, correlates with the intestinal phenotype of gastric adenocarcinomas. Pathology 38:548–554, 2007/03/31 ednPubMedCrossRefGoogle Scholar
  18. 18.
    Tanaka T, Jiang S, Hotta H, Takano K, Iwanari H, Sumi K, Daigo K, Ohashi R, Sugai M, Ikegame C, Umezu H, Hirayama Y, Midorikawa Y, Hippo Y, Watanabe A, Uchiyama Y, Hasegawa G, Reid P, Aburatani H, Hamakubo T, Sakai J, Naito M, Kodama T (2006) Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. J Pathol 208:662–672, 2006/01/10 edn. doi: 10.1002/path.1928 PubMedCrossRefGoogle Scholar
  19. 19.
    Sladek FM, Zhong WM, Lai E, Darnell JE Jr (1990) Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev 4:2353–2365, 1990/12/01 ednPubMedCrossRefGoogle Scholar
  20. 20.
    Takano K, Hasegawa G, Jiang S, Kurosaki I, Hatakeyama K, Iwanari H, Tanaka T, Hamakubo T, Kodama T, Naito M (2009) Immunohistochemical staining for P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha may complement mucin phenotype of differentiated-type early gastric carcinoma. Pathol Int 59:462–470, 2009/07/01 edn. doi: 10.1111/j.1440-1827.2009.02394.x PubMedCrossRefGoogle Scholar
  21. 21.
    Sugai M, Umezu H, Yamamoto T, Jiang S, Iwanari H, Tanaka T, Hamakubo T, Kodama T, Naito M (2008) Expression of hepatocyte nuclear factor 4 alpha in primary ovarian mucinous tumors. Pathol Int 58:681–686, 2008/10/11 edn. doi: 10.1111/j.1440-1827.2008.02293.x PubMedCrossRefGoogle Scholar
  22. 22.
    Chu PG, Weiss LM (2004) Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon. Am J Clin Pathol 121:884–892, 2004/06/17 edn. doi: 10.1309/a09e-rymf-r64n-erdw PubMedCrossRefGoogle Scholar
  23. 23.
    O’Connell FP, Wang HH, Odze RD (2005) Utility of immunohistochemistry in distinguishing primary adenocarcinomas from metastatic breast carcinomas in the gastrointestinal tract. Arch Pathol Lab Med 129:338–347, 2005/03/02 edn. doi: 10.1043/1543-2165(2005)129<338:uoiidp>2.0.co;2 PubMedGoogle Scholar
  24. 24.
    Tot T (2000) The role of cytokeratins 20 and 7 and estrogen receptor analysis in separation of metastatic lobular carcinoma of the breast and metastatic signet ring cell carcinoma of the gastrointestinal tract. APMIS 108:467–472, 2000/10/12 ednPubMedCrossRefGoogle Scholar
  25. 25.
    Chu PG, Chung L, Weiss LM, Lau SK (2011) Determining the site of origin of mucinous adenocarcinoma: an immunohistochemical study of 175 cases. Am J Surg Pathol 35:1830–1836, 2011/09/02 edn. doi: 10.1097/PAS.0b013e3182299c25 PubMedCrossRefGoogle Scholar
  26. 26.
    Werling RW, Yaziji H, Bacchi CE, Gown AM (2003) CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol 27:303–310, 2003/02/27 ednPubMedCrossRefGoogle Scholar
  27. 27.
    Dennis JL, Hvidsten TR, Wit EC, Komorowski J, Bell AK, Downie I, Mooney J, Verbeke C, Bellamy C, Keith WN, Oien KA (2005) Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm. Clin Cancer Res 11:3766–3772, 2005/05/18 edn. doi: 10.1158/1078-0432.ccr-04-2236 PubMedCrossRefGoogle Scholar
  28. 28.
    Moll R, Lowe A, Laufer J, Franke WW (1992) Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol 140:427–447, 1992/02/01 ednPubMedCentralPubMedGoogle Scholar
  29. 29.
    Nguyen MD, Plasil B, Wen P, Frankel WL (2006) Mucin profiles in signet-ring cell carcinoma. Arch Pathol Lab Med 130:799–804PubMedGoogle Scholar
  30. 30.
    Lau SK, Weiss LM, Chu PG (2004) Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol 122:61–69PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • R. S. van der Post
    • 1
    Email author
  • P. Bult
    • 1
  • I. P. Vogelaar
    • 2
  • M. J. L. Ligtenberg
    • 1
    • 2
  • N. Hoogerbrugge
    • 2
  • J. H. van Krieken
    • 1
  1. 1.824 Department of PathologyRadboud university medical centerNijmegenThe Netherlands
  2. 2.Department of Human GeneticsRadboud university medical centerNijmegenThe Netherlands

Personalised recommendations