J Gastric Cancer.  2011 Mar;11(1):23-30.

Clinicopathological Characteristics of Alpha-Fetoprotein-Producing Gastric Cancer

• Chun H
• Kwon SJ

Abstract

PURPOSE
alpha-fetoprotein (AFP)-producing gastric cancer is a rare tumor with high rates of liver metastasis and a poor prognosis. Many studies have been performed but there have been no comprehensive investigations of the clinicopathological and prognosis.
MATERIALS AND METHODS
Six hundred ninety four patients with gastric cancer who underwent a curative gastric resection in Hanyang University Hospital from February 2001 to December 2008 were evaluated retrospectively after excluding active or chronic hepatits, liver cirrhosis and preoperative distant metastasis. Among them, thirty five patients had an elevated serum level of AFP (>7 ng/ml) preoperatively. The clinicopathological features of AFP-producing gastric cancer were analyzed.
RESULTS
There was poorer differentiation, a higher incidence of lymph node metastasis, more marked lymphatic and vascular invasion in the AFP-positive group than in the AFP-negative group. The 5-year survival rate of the AFP-positive group was significantly poorer than that in the AFP-negative group (66% vs. 80%, P=0.002). A significantly higher incidence of liver metastasis was observed in the AFP-positive group than in the AFP-negative group (14.3% vs. 3.6%, P=0.002) with a shorter median time period from the operation to the metachronous liver metastasis (3.7 months vs. 14.1 months, P=0.043). Multivariate survival analysis revealed the depth of invasion, degree of lymph node metastasis and AFP-positivity to be the independent prognostic factors.
CONCLUSIONS
AFP-producing gastric cancers have an aggressive behavior with a high metastatic potential to the liver. In addition, their clinicopathological features are quite different from the more common AFP-negative gastric cancer.

Keyword

Stomach neoplasms; Alpha-fetoproteins; Liver metastasis; Prognosis

MeSH Terms

alpha-Fetoproteins
Humans
Incidence
Liver
Liver Cirrhosis
Lymph Nodes
Neoplasm Metastasis
Prognosis
Retrospective Studies
Stomach Neoplasms
Survival Rate
alpha-Fetoproteins

Figure

• 

  Fig. 1 Patients selection.

• 

  Fig. 2 Relationship between preoperative serum AFP level and N stage. There was a signifi cant increase of median serum AFP level according to each N stage (2.3 vs. 2.4 vs. 2.7 vs. 3.4, P=0.001). AFP = alpha-fetoprotein.

• 

  Fig. 3 Relationship between preoperative serum AFP level and liver metastasis. There was a signifi cant increase of median AFP level in liver metastasis positive group compared to liver metastasis negative group (6.5 vs. 2.3, P=0.000). AFP = alpha-fetoprotein.

• 

  Fig. 4 Overall survival curves of gastric cancer patients with liver metastasis according to AFP-positivity (5-year survival rate 20% vs. 0%, median survival time 26.4 months vs. 11.4 months). AFP = alpha-fetoprotein.

Reference

1. Bergstrand CG, Czar B. Demonstration of a new protein fraction in serum from the human fetus. Scand J Clin Lab Invest. 1956. 8:174.

2. Nishimura H, Okamoto Y, Takahashi M, Fujita T. Occurrence of alpha-fetoprotein, Regan isoenzyme, and variant alkaline phosphatase in the serum of a patient with gastric cancer. Gastroenterology. 1976. 71:497–499.

3. Bourreille J, Metayer P, Sauger F, Matray F, Fondimare A. Existence of alpha feto protein during gastric-origin secondary cancer of the liver. Presse Med. 1970. 78:1277–1278.

4. Chang YC, Nagasue N, Abe S, Kohno H, Yamanoi A, Uchida M, et al. The characters of AFP-producing early gastric cancer. Nippon Geka Gakkai Zasshi. 1990. 91:1574–1580.

5. Motoyama T, Aizawa K, Watanabe H, Fukase M, Saito K. Alpha-Fetoprotein producing gastric carcinomas: a comparative study of three different subtypes. Acta Pathol Jpn. 1993. 43:654–661.

6. Chang YC, Nagasue N, Abe S, Taniura H, Kumar DD, Nakamura T. Comparison between the clinicopathologic features of AFP-positive and AFP-negative gastric cancers. Am J Gastroenterol. 1992. 87:321–325.

7. Koide N, Nishio A, Igarashi J, Kajikawa S, Adachi W, Amano J. Alpha-fetoprotein-producing gastric cancer: histochemical analysis of cell proliferation, apoptosis and angiogenesis. Am J Gastroenterol. 1999. 94:1658–1663.

8. Amemiya H, Kono K, Mori Y, Takahashi A, Ichihara F, Iizuka H, et al. High frequency of c-Met expression in gastric cancers producing alpha-fetoprotein. Oncology. 2000. 59:145–151.

9. Sobin LH, Wittekind CH, editors. TNM Classifi cation of Malignant Tumors. 2002. 6th ed. New York, NY: Wiley-Liss.

10. Gitlin D, Boesman M. Serum alpha-fetoprotein, albumin, and gamma-G-globulin in the human conceptus. J Clin Invest. 1966. 45:1826–1838.

11. Ramsey WH, Wu GY. Hepatocellular carcinoma: update on diagnosis and treatment. Dig Dis. 1995. 13:81–91.

12. Gitlin D, Perricelli A, Gitlin GM. Synthesis of alpha-fetoprotein by liver, yolk sac, and gastrointestinal tract of the human conceptus. Cancer Res. 1972. 32:979–982.

13. Taguchi J, Yano H, Sueda J, Yamaguchi R, Kojiro M, Shirouzu G, et al. Alpha-Fetoprotein-producing rectal carcinoma--a case report. Kurume Med J. 1997. 44:339–348.

14. Sugaya Y, Sugaya H, Kuronuma Y, Hisauchi T, Harada T. A case of gallbladder carcinoma producing both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA). Gastroenterol Jpn. 1989. 24:325–331.

15. Hiroshima K, Iyoda A, Toyozaki T, Haga Y, Baba M, Fujisawa T, et al. Alpha-fetoprotein-producing lung carcinoma: report of three cases. Pathol Int. 2002. 52:46–53.

16. Takayama H. A case of bladder cancer producing alpha-fetoprotein (AFP). Hinyokika Kiyo. 1995. 41:387–389.

17. Stuart KE, Anand AJ, Jenkins RL. Hepatocellular carcinoma in the United States. Prognostic features, treatment outcome, and survival. Cancer. 1996. 77:2217–2222.

18. Kim T, Yu WS. Prognostic value of preoperative serum alpha-fetoprotein level in resectable gastric cancer. J Korean Gastric Cancer Assoc. 2003. 3:33–37.

19. Joo YH, Jung HY, Kang GH, Youn HJ, Kim SY, Yang SK, et al. Clinico-pathological characteristics of the alpha-fetoprotein producing gastric carcinoma. Korean J Gastroenterol. 2000. 36:54–60.

20. Chang YC, Nagasue N, Kohno H, Taniura H, Uchida M, Yamanoi A, et al. Clinicopathologic features and long-term results of alpha-fetoprotein-producing gastric cancer. Am J Gastroenterol. 1990. 85:1480–1485.

21. Kono K, Amemiya H, Sekikawa T, Iizuka H, Takahashi A, Fujii H, et al. Clinicopathologic features of gastric cancers producing alpha-fetoprotein. Dig Surg. 2002. 19:359–365.

22. Liu X, Cheng Y, Sheng W, Lu H, Xu Y, Long Z, et al. Clinicopathologic features and prognostic factors in alpha-fetoprotein-producing gastric cancers: analysis of 104 cases. J Surg Oncol. 2010. 102:249–255.

23. McIntire KR, Waldmann TA, Moertel CG, Go VL. Serum alpha-fetoprotein in patients with neoplasms of the gastrointestinal tract. Cancer Res. 1975. 35:991–996.

24. Kumashiro Y, Yao T, Aishima S, Hirahashi M, Nishiyama K, Yamada T, et al. Hepatoid adenocarcinoma of the stomach: histogenesis and progression in association with intestinal phenotype. Hum Pathol. 2007. 38:857–863.

25. Kaji M, Yonemura Y, Harada S, Liu X, Terada I, Yamamoto H. Participation of c-met in the progression of human gastric cancers: anti-c-met oligonucleotides inhibit proliferation or invasiveness of gastric cancer cells. Cancer Gene Ther. 1996. 3:393–404.

26. Sato Y, Nishimaki T, Date K, Shirai Y, Kurosaki I, Saito Y, et al. Successful resection of metachronous liver metastasis from alpha-fetoprotein-producing gastric cancer: report of a case. Surg Today. 1999. 29:1075–1078.

27. Tsurumachi T, Yamamoto H, Watanabe K, Honda I, Watanabe S, Yamada S, et al. Resection of liver metastasis from alpha-fetoprotein-producing early gastric cancer: report of a case. Surg Today. 1997. 27:563–566.