No abstract

No abstract

Background. Cancer in pregnancy is rare and hepatocellular carcinoma (HCC) in pregnancy even rarer. The impact of pregnancy on the prognosis of patients with different types of cancer remains controversial. Reported cases of HCC in pregnancy are largely isolated and highly scattered. Thus, the effect of pregnancy on the prognosis of patients with HCC and the risk factors of developing HCC in pregnancy are not well documented. Methods. A series of five patients with HCC in pregnancy seen at two different centers is reported. A Medlar search for articles between 1957 and 1993 with the key words“Hepatocellular Carcinoma” and “Pregnancy” was conducted. All reported cases were combined and analyzed in terms of race, age, parity, hepatitis B surface antigen status, cirrhosis, serum alpha‐fetoprotein (AFP) levels at presentation, history of taking oral contraceptive pills and fetal and maternal outcome. The impact of pregnancy on 12 other malignancies as reported in the medical literature also was reviewed. Results. To the authors' knowledge, The five cases reported here constitute the largest series of HCC in pregnancy. A literature search revealed 23 additional cases. Analysis of the 28 cases suggests that the rarity of HCC in pregnancy results from a combination of three factors: the male predominance of HCC, the late age at which the tumor usually presents in women, and decreased fertility in women with advanced cirrhosis (hepatitis is a predisposing factor for HCC development). Long term use of oral contraceptives and high parity enhance the risk. Elevated AFP level is useful for diagnosis. The median survival is shorter than for patients who are not pregnant. There is no significant difference in survival between pregnant and not pregnant women matched by tumor stage, age, and other clinical parameters in most malignancies except in some tumors like lymphoma, thyroid cancer, and nasopharyngeal carcinoma. Conclusion. Pregnancy has an adverse effect on the prognosis of patients with HCC, lymphoma, thyroid cancer, and nasopharyngeal carcinoma but not of most other malignancies. Measurement of AFP level is recommended for screening HCC in pregnant women at high risk. Cancer 1995;75:2669–76.

As one of major epigenetic changes responsible for tumor suppressor gene inactivation in the development of cancer, promoter hypermethylation was proposed as a marker to define novel tumor suppressor genes. In the current study we identified ZIC1 (Zic family member 1, odd-paired Drosophila homolog) as a novel tumor suppressor gene silenced through promoter hypermethylation in gastric cancer, the second leading cause of cancer death worldwide. In all of gastric cancer cells lines examined, ZIC1 expression was downregulated and such downregulation was accompanied with the hypermethylation of ZIC1 promoter. Demethylation treatment with 5-aza-2'-deoxycytidine (Aza) reversed ZIC1 downregulation, highlighting the importance of promoter methylation to ZIC1 downregulation in gastric cancer cells. Notably, ZIC1 expression was significantly downregulated in primary gastric carcinoma tissues in comparison with non-tumor adjacent gastric tissues (p<0.01). Accordingly, promoter methylation of ZIC1 was frequently detected in primary gastric carcinoma tissues (94.6%, 35/37) but not normal gastric tissues, indicating that promoter hypermethylation mediated ZIC1 downregulation may play an important role in gastric carcinogenesis. Indeed, ectopic expression of ZIC1 led to the growth inhibition of gastric cancer cells through the induction of S-phase cell cycle arrest (p<0.01). Our results revealed ZIC1 as a novel candidate tumor suppressor gene downregulated through promoter hypermethylation in gastric cancer.