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The diagnostic value of pCEA, mCEA, AFP and CK19 in differentiating primary and metastatic carcinoma of liver

Year 2016, , 39 - 46, 01.01.2016
https://doi.org/10.5505/abantmedj.2016.94557

Abstract

INTRODUCTION: Hepatocellular carcinoma HCC represent tumors that originate from hepatocytes or show hepatocellular differentiation, constituting 80-85% of primary malignant tumors of liver. Metastatic carcinomas are mostly seen in liver, as well. However, differential diagnosis of primary and metastatic tumors can be difficult especially while evaluating tru-cut biopsies. In this study, we evaluated immunohistochemical expression profiles of CK19, AFP, mCEA and pCEA in patients with HCC, cholangiocellular carcinoma CCC and metastatic adenocarcinoma diagnosed based on histopathological, clinical and radiological findings. METHODS: : A total of 75 cases 39 HCC, 3 CCC and 33 metastatic adenocarcinoma were included. Immunohistochemical staining pCEA, mCEA, AFP and CK19 were performed on needle biopsy samples larger than 15 mm and wedge resection materials.RESULTS: Mean age of HCC patients was 49, 5 range 15-75 and male/female ratio was 3.8: 1. Six 15.2% cases of HCC were classified as grade I, 22 56.4% as grade II, 9 23% as grade III and 2 5.4% as grade IV. CCC patients were male and mean age was 44. AFP was negative in 3 CCC cases. Of 33 cases with metastatic adenocarcinoma, male / female ratio was 1: 1. And mean age was 54.2 range 37-74 . CK19 was stained positive in 23 cases. Tumors originating from pancreas and gallbladder showed diffuse positivity. DISCUSSION AND CONCLUSION: CK19 was found to be an important marker in differentiating HCC and CCC. However, it cannot be used in differential diagnosis of CCC and metastatic adenocarcinoma. Canalicular staining of pCEAin HCC is useful in differentiating HCC and metastatic adenocarcinomas. On the contrary, mCEA is strongly expressed in metastatic adenocarcinomas, suggesting it also could be a useful marker in differentiating HCC and metastatic adenocarcinomas. Due to low sensitivity and specificity of AFP expression, it cannot be used as a reliable marker in differential diagnosis of HCC and metastatic tumors.

References

  • 1. Güllüoğlu MG, Özlük Y, Fidan Ö, Demir D, Çevikbaş U. Karaciğer kitle biyopsilerinde ayırıcı tanıda immünhistokimyanın yeri. Türk Onkoloji Dergisi, 2005. 20(1):p. 13-19
  • 2. Lau SK, Prakash S, Geller SA, Alsabeh R.Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol, 2002. 33(12): p. 1175-81.
  • 3. Kasper HU,Drebber U,Dries V,Dienes HP.[Liver metastases: incidence and histogenesis]. Z Gastroenterol, 2005. 43(10): p. 1149-57.
  • 4. Karabork A, Kaygusuz G, Ekinci C.The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma. Pathol Res Pract, 2010. 206(8): p. 572-7.
  • 5. Balaton AJ, Nehama-Sibony M, Gotheil C, Callard P, Baviera EE.Distinction between hepatocellular carcinoma, cholangiocarcinoma, and metastatic carcinoma based on immunohistochemical staining for carcinoembryonic antigen and for cytokeratin 19 on paraffin sections. J Pathol, 1988. 156(4): p. 305-10.
  • 6. Hurlimann J, Gardiol D.Immunohistochemistry in the differential diagnosis of liver carcinomas. Am J Surg Pathol, 1991. 15(3): p. 280-8.
  • 7. Leong AS, Sormunen RT, Tsui WM, Liew CT. Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma. Histopathology, 1998. 33(4): p. 318-24.
  • 8. Lee JI, Lee JW, Kim JM, Kim JK, Chung HJ, Kim YS. Prognosis of hepatocellular carcinoma expressing cytokeratin 19: comparison with other liver cancers. World J Gastroenterol, 2012. 18(34): p. 4751-7.
  • 9. Chen ZE, Lin F. Application of immunohistochemistry in gastrointestinal and liver neoplasm:new markers and evolving practice Arch Pathol Lab Med. 2015.139(1):p.14-23.
  • 10. Jain, D., Tissue diagnosis of hepatocellular carcinoma. J Clin Exp Hepatol, 2014. 4(Suppl 3): p. S67-73.
  • 11. Ho M, Kim H.Glypican-3: a new target for cancer immunotherapy. Eur J Cancer, 2011. 47(3): p. 333-8.
  • 12. Marrero JA.Modern diagnosis of hepatocellular carcinoma: Utilization of liver biopsy and genomic markers. J Hepatol, 2009. 50(4): p. 659-61.
  • 13. Porcell AI, De Young BR, Proca DM, Frankel WL.Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers. Mod Pathol, 2000. 13(7): p. 773-8.
  • 14. Shimonishi T, Miyazaki K, NakanumaY.Cytokeratin profile relates to histological subtypes and intrahepatic location of intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of liver. Histopathology, 2000. 37(1): p. 55-63.
  • 15. Fischer HP,Altmannsberger M, Weber K, Osborn M.Keratin polypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects. Am J Pathol, 1987. 127(3): p. 530-7.
  • 16. Carrozza MJ, Calafati SA, Edmonds PR.Immunocytochemical localization of polyclonal carcinoembryonic antigen in hepatocellular carcinomas. Acta Cytol, 1991. 35(2): p. 221-4.
  • 17. Brumm C, Schulze C, Charels K, Morohoshi T, Kloppel G.The significance of alpha-fetoprotein and other tumour markers in differential immunocytochemistry of primary liver tumours. Histopathology, 1989. 14(5): p. 503-13.
  • 18. Ma CK, Zarbo RJ, Frierson HF, Lee MW.Comparative immunohistochemical study of primary and metastatic carcinomas of the liver. Am J Clin Pathol, 1993. 99(5): p. 551-7.
  • 19. Sheahan K, O'Brien MJ, Burke B, Dervan PA, O'Keane JC, Gottlieb LS, Zamcheck N.Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies. Am J Clin Pathol, 1990. 94(2): p. 157-64.
  • 20. Minervini MI, Demetris AJ, Lee RG, Carr BI, Madariaga J, Nalesnik MA.Utilization of hepatocyte-specific antibody in the immunocytochemical evaluation of liver tumors. Mod Pathol, 1997. 10(7): p. 686-92.
  • 21. Christensen WN, Boitnott JK , Kuhajda FP.Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma. Mod Pathol, 1989. 2(1): p. 8-12.
  • 22. Ganjei P, Nadji M, Albores-Saavedra J, Morales AR.Histologic markers in primary and metastatic tumors of the liver. Cancer, 1988. 62(9): p. 1994-8.
  • 23. Ma WJ, Wang HY, Teng LS.Correlation analysis of preoperative serum alphafetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. World J Surg Oncol, 2013. 11: p. 212.
  • 24. Kashala LO, Kalengayi MM, Essex M.Alpha-fetoprotein synthesis in human hepatocellular carcinoma: correlation with hepatitis B surface antigen expression. Cancer Invest, 1992. 10(6): p. 513-22.
  • 25. Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L.Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer, 1985. 55(1): p. 124-35.
  • 26. Imoto M, Nishimura D, Fukuda Y, Sugiyama K, Kumada T, Nakano S.Immunohistochemical detection of alphafetoprotein, carcinoembryonic antigen, and ferritin in formalin-paraffin sections from hepatocellular carcinoma. Am J Gastroenterol, 1985. 80(11): p. 902-6.
  • 27. Thung SN,Gerber MA, Sarno E, Popper H.Distribution of five antigens in hepatocellular carcinoma. Lab Invest, 1979. 41(2): p. 101-5.
  • 28. Fucich LF, Cheles MK, Thung SN, Gerber MA, Marrogi AJ.Primary vs metastatic hepatic carcinoma. An immunohistochemical study of 34 cases. Arch Pathol Lab Med, 1994. 118(9): p. 927-30.

Karaciğerin primer ve metastatik karsinomlarının ayrımında pCEA, mCEA, AFP ve CK19' un tanısal değeri

Year 2016, , 39 - 46, 01.01.2016
https://doi.org/10.5505/abantmedj.2016.94557

Abstract

GİRİŞ ve AMAÇ: Hepatosellüler karsinom HCC hepatositlerden köken alan ya da hepatosellüler diferansiyasyon gösteren, primer karaciğer tümörlerinin %80-85’ini oluşturan malign tümördür. Karaciğerin primer ve metastatik malign tümörlerinin ayırıcı tanısında özellikle tru–cut biopsilerde tanısal güçlükle karşılaşılmaktadır. Karaciğer, metastatik karsinomların en fazla izlendiği organ olması nedeni ile bu ayrımın kesin bir şekilde yapılması önem kazanmaktadır. Bu çalışmada, klinik ve radyolojik bulgular eşliğinde histopatolojik olarak tanı almış primer HCC, kolanjiosellüler karsinoma KCC ve metastatik adenokarsinomlarda immunohistokimyasal CK19, AFP, mCEA ve pCEA’nın boyanma profilleri araştırılmıştır.YÖNTEM ve GEREÇLER: 39 hepatosellüler karsinom, 33 metastatik adenokarsinom ve 3 KCC ait olmak üzere toplam 75 olgunun 15 mm’den büyük iğne biyopsileri ve wedge rezeksiyon materyalleri çalışmaya dahil edildi. Olgulara immünhistokimyasal olarak pCEA, mCEA, AFP ve CK19 uygulandı.BULGULAR: 39 HCC olgusunun yaş ortalaması 49,5 15-75 tespit edilmiş olup, erkek/kadın oranı 3,8: 1 dir. HCC olgularının 6’sı grade I %15.2 , 22’si grade II %56.4 , 9’u grade III %23 , 2’si grade IV %5.4 idi. Üç KCC olgumuzda yaş ortalaması 44 olup, 3’ü de erkektir. Üç olguda da AFP’nin negatif olması dikkat çekicidir. 33 metastatik karaciğer tümörünün kadın/erkek oranı 1: 1dir. Yaş ortalaması 54.2 37-74 idir. CK19, 23 %60.6 olguda pozitif olarak bulunmuştur. Pankreas ve safra kesesi kaynaklı metastatik tümörlerin hepsinde yaygın pozitiflik saptanmıştır.TARTIŞMA ve SONUÇ: CK19, HCC ve KCC ayırıcı tanısında önemli bir belirleyiciyken metastatik adenokarsinom ve KCC ayrımında yardımcı değildir. pCEA’nın HCC’lerde kanaliküler tipte boyanması HCC’ye özgü bir boyanma olarak metastatik adenokarsinomlardan ayrımında önemlidir. mCEA ise metastatik adenokarsinomlarda kuvvetli intrasitoplazmik ekspresyon gösterdiğinden HCC ve metastaz ayrımında yardımcı bir markerdir. AFP ekspresyonunun spesifite ve sensitivitesi düşük olduğundan metastaz ve HCC ayırıcı tanısında çok faydalı değildir.

References

  • 1. Güllüoğlu MG, Özlük Y, Fidan Ö, Demir D, Çevikbaş U. Karaciğer kitle biyopsilerinde ayırıcı tanıda immünhistokimyanın yeri. Türk Onkoloji Dergisi, 2005. 20(1):p. 13-19
  • 2. Lau SK, Prakash S, Geller SA, Alsabeh R.Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol, 2002. 33(12): p. 1175-81.
  • 3. Kasper HU,Drebber U,Dries V,Dienes HP.[Liver metastases: incidence and histogenesis]. Z Gastroenterol, 2005. 43(10): p. 1149-57.
  • 4. Karabork A, Kaygusuz G, Ekinci C.The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma. Pathol Res Pract, 2010. 206(8): p. 572-7.
  • 5. Balaton AJ, Nehama-Sibony M, Gotheil C, Callard P, Baviera EE.Distinction between hepatocellular carcinoma, cholangiocarcinoma, and metastatic carcinoma based on immunohistochemical staining for carcinoembryonic antigen and for cytokeratin 19 on paraffin sections. J Pathol, 1988. 156(4): p. 305-10.
  • 6. Hurlimann J, Gardiol D.Immunohistochemistry in the differential diagnosis of liver carcinomas. Am J Surg Pathol, 1991. 15(3): p. 280-8.
  • 7. Leong AS, Sormunen RT, Tsui WM, Liew CT. Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma. Histopathology, 1998. 33(4): p. 318-24.
  • 8. Lee JI, Lee JW, Kim JM, Kim JK, Chung HJ, Kim YS. Prognosis of hepatocellular carcinoma expressing cytokeratin 19: comparison with other liver cancers. World J Gastroenterol, 2012. 18(34): p. 4751-7.
  • 9. Chen ZE, Lin F. Application of immunohistochemistry in gastrointestinal and liver neoplasm:new markers and evolving practice Arch Pathol Lab Med. 2015.139(1):p.14-23.
  • 10. Jain, D., Tissue diagnosis of hepatocellular carcinoma. J Clin Exp Hepatol, 2014. 4(Suppl 3): p. S67-73.
  • 11. Ho M, Kim H.Glypican-3: a new target for cancer immunotherapy. Eur J Cancer, 2011. 47(3): p. 333-8.
  • 12. Marrero JA.Modern diagnosis of hepatocellular carcinoma: Utilization of liver biopsy and genomic markers. J Hepatol, 2009. 50(4): p. 659-61.
  • 13. Porcell AI, De Young BR, Proca DM, Frankel WL.Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers. Mod Pathol, 2000. 13(7): p. 773-8.
  • 14. Shimonishi T, Miyazaki K, NakanumaY.Cytokeratin profile relates to histological subtypes and intrahepatic location of intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of liver. Histopathology, 2000. 37(1): p. 55-63.
  • 15. Fischer HP,Altmannsberger M, Weber K, Osborn M.Keratin polypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects. Am J Pathol, 1987. 127(3): p. 530-7.
  • 16. Carrozza MJ, Calafati SA, Edmonds PR.Immunocytochemical localization of polyclonal carcinoembryonic antigen in hepatocellular carcinomas. Acta Cytol, 1991. 35(2): p. 221-4.
  • 17. Brumm C, Schulze C, Charels K, Morohoshi T, Kloppel G.The significance of alpha-fetoprotein and other tumour markers in differential immunocytochemistry of primary liver tumours. Histopathology, 1989. 14(5): p. 503-13.
  • 18. Ma CK, Zarbo RJ, Frierson HF, Lee MW.Comparative immunohistochemical study of primary and metastatic carcinomas of the liver. Am J Clin Pathol, 1993. 99(5): p. 551-7.
  • 19. Sheahan K, O'Brien MJ, Burke B, Dervan PA, O'Keane JC, Gottlieb LS, Zamcheck N.Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies. Am J Clin Pathol, 1990. 94(2): p. 157-64.
  • 20. Minervini MI, Demetris AJ, Lee RG, Carr BI, Madariaga J, Nalesnik MA.Utilization of hepatocyte-specific antibody in the immunocytochemical evaluation of liver tumors. Mod Pathol, 1997. 10(7): p. 686-92.
  • 21. Christensen WN, Boitnott JK , Kuhajda FP.Immunoperoxidase staining as a diagnostic aid for hepatocellular carcinoma. Mod Pathol, 1989. 2(1): p. 8-12.
  • 22. Ganjei P, Nadji M, Albores-Saavedra J, Morales AR.Histologic markers in primary and metastatic tumors of the liver. Cancer, 1988. 62(9): p. 1994-8.
  • 23. Ma WJ, Wang HY, Teng LS.Correlation analysis of preoperative serum alphafetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. World J Surg Oncol, 2013. 11: p. 212.
  • 24. Kashala LO, Kalengayi MM, Essex M.Alpha-fetoprotein synthesis in human hepatocellular carcinoma: correlation with hepatitis B surface antigen expression. Cancer Invest, 1992. 10(6): p. 513-22.
  • 25. Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L.Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer, 1985. 55(1): p. 124-35.
  • 26. Imoto M, Nishimura D, Fukuda Y, Sugiyama K, Kumada T, Nakano S.Immunohistochemical detection of alphafetoprotein, carcinoembryonic antigen, and ferritin in formalin-paraffin sections from hepatocellular carcinoma. Am J Gastroenterol, 1985. 80(11): p. 902-6.
  • 27. Thung SN,Gerber MA, Sarno E, Popper H.Distribution of five antigens in hepatocellular carcinoma. Lab Invest, 1979. 41(2): p. 101-5.
  • 28. Fucich LF, Cheles MK, Thung SN, Gerber MA, Marrogi AJ.Primary vs metastatic hepatic carcinoma. An immunohistochemical study of 34 cases. Arch Pathol Lab Med, 1994. 118(9): p. 927-30.
There are 28 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Hesna Müzeyyen Astarcı This is me

Gülzade Özyalvaçlı This is me

Ayşe Sertçelik This is me

Publication Date January 1, 2016
Published in Issue Year 2016

Cite

APA Astarcı, H. M., Özyalvaçlı, G., & Sertçelik, A. (2016). Karaciğerin primer ve metastatik karsinomlarının ayrımında pCEA, mCEA, AFP ve CK19’ un tanısal değeri. Abant Medical Journal, 5(1), 39-46. https://doi.org/10.5505/abantmedj.2016.94557
AMA Astarcı HM, Özyalvaçlı G, Sertçelik A. Karaciğerin primer ve metastatik karsinomlarının ayrımında pCEA, mCEA, AFP ve CK19’ un tanısal değeri. Abant Med J. January 2016;5(1):39-46. doi:10.5505/abantmedj.2016.94557
Chicago Astarcı, Hesna Müzeyyen, Gülzade Özyalvaçlı, and Ayşe Sertçelik. “Karaciğerin Primer Ve Metastatik karsinomlarının ayrımında PCEA, MCEA, AFP Ve CK19’ Un tanısal değeri”. Abant Medical Journal 5, no. 1 (January 2016): 39-46. https://doi.org/10.5505/abantmedj.2016.94557.
EndNote Astarcı HM, Özyalvaçlı G, Sertçelik A (January 1, 2016) Karaciğerin primer ve metastatik karsinomlarının ayrımında pCEA, mCEA, AFP ve CK19’ un tanısal değeri. Abant Medical Journal 5 1 39–46.
IEEE H. M. Astarcı, G. Özyalvaçlı, and A. Sertçelik, “Karaciğerin primer ve metastatik karsinomlarının ayrımında pCEA, mCEA, AFP ve CK19’ un tanısal değeri”, Abant Med J, vol. 5, no. 1, pp. 39–46, 2016, doi: 10.5505/abantmedj.2016.94557.
ISNAD Astarcı, Hesna Müzeyyen et al. “Karaciğerin Primer Ve Metastatik karsinomlarının ayrımında PCEA, MCEA, AFP Ve CK19’ Un tanısal değeri”. Abant Medical Journal 5/1 (January 2016), 39-46. https://doi.org/10.5505/abantmedj.2016.94557.
JAMA Astarcı HM, Özyalvaçlı G, Sertçelik A. Karaciğerin primer ve metastatik karsinomlarının ayrımında pCEA, mCEA, AFP ve CK19’ un tanısal değeri. Abant Med J. 2016;5:39–46.
MLA Astarcı, Hesna Müzeyyen et al. “Karaciğerin Primer Ve Metastatik karsinomlarının ayrımında PCEA, MCEA, AFP Ve CK19’ Un tanısal değeri”. Abant Medical Journal, vol. 5, no. 1, 2016, pp. 39-46, doi:10.5505/abantmedj.2016.94557.
Vancouver Astarcı HM, Özyalvaçlı G, Sertçelik A. Karaciğerin primer ve metastatik karsinomlarının ayrımında pCEA, mCEA, AFP ve CK19’ un tanısal değeri. Abant Med J. 2016;5(1):39-46.