Patients with Positive Epithelial-Mesenchymal Transition Markers Have Lowest Survival Rate

Hepatocellular carcinoma (HCC) or primary liver hepatitis B virus (HBV) or hepatitis C virus (HCV). In the U.S., the National Cancer Institute (NCI) estimates that 15,000 men and 6,000 women are diagnosed with HCC each year. Worldwide, HCC accounts for 632,000 cases with the highest regions being Western Pacific and Africa according to a 2004 World Health Organization (WHO) report.

Researchers from Taipei Veterans General Hospital investigated the molecular mechanisms of HCC, one of the most common tumors found in Taiwan and largely caused by the high prevalence (15%-20%) of HBV in the country. The study, funded in part by a grant from the National Science Council, is the first to provide a comprehensive profile of multiple Epithelial-Mesenchymal Transition (EMT) markers and to demonstrate that Snail and Twist, but not Slug, are the major inducers of EMT in HCC. Results of the study are published in the November issue of Hepatology, a journal of the American Association for the Study of Liver Diseases.

EMT is critical in the development of invasiveness and metastatic potential of human cancers, and described as process where epithelial cells no longer adhere to one another, taking on fibroblastic properties. The EMT process is initiated by suppression of E-cadherin function through the major EMT regulators (Snail, Slug, and Twist). E-cadherin (calcium dependent adhesion molecules) is a type of protein found in the epithelial cells that ensure tissue cells bind together. When E-cadherin function is lost, cancer is able to progress and metastasize.

Professor Jaw-Ching Wu and colleagues obtained samples of primary HCC with adjacent non-tumorous liver tissues from 123 patients who had hepatic resection surgery between 1990 and 2002 at Taipei Veterans General Hospital. Reduced E-cadherin function was observed in 60.2% of patients. “We found a significant decrease in cancer-free intervals and overall survival for those patients who had a reduction in E-cadherin function,” explained Dr. Wu. A downregulated expression of E-cadherin was also associated with large tumor size and multi-nodular tumors.

Results show that co-expression Snail and Twist (transcription factors or proteins that control when genes are switched on or off) indicates the worst prognosis for HCC patients. “Our research is the first to prove that the two proteins (Snail and Twist) work independently, but together promote EMT,” noted Dr. Wu.

According to the study, overexpression of Twist is correlated with HCV-related HCC, partially explaining the highly invasive behavior and poor prognosis for patients with this form of liver cancer. Dr Wu added, “Our results provide essential information for determining HCC prognosis in patients and identifies possible new treatments for future HCC management.”

Source: Wiley - Blackwell

Although Helicobacter pylori (H. pylori) has been classified as a class I (or definite) carcinogen by World Health Organization (WHO), the controversy as to why only a minority of infected patients develop gastric cancer still remains. Moreover, in Asian countries such as Indonesia, Japan, China, and Thailand, where the H. pylori infection rates are similar, there is a significant difference regarding the outcome of gastric cancer. That fact has been termed the “Asian paradox”.

A research article published in the World Journal of Gastroenterology addresses this question. Research, led by Murdani Abdullah, MD from Division of Gastroenterology, Department of Internal Medicine, University of Indonesia, was based on the old concept of a cascade of mucosal changes that develops from acute/chronic gastritis to gastric cancer as proposed by P. Correa. The difference in the pattern of H. pylori-associated gastritis may explain the difference in the incidence of gastric cancer between Indonesia and Japan. Previous studies have never evaluated the cascade of gastric mucosal changes prior to gastric cancer. In this research, the transformation of gastric mucosa that is induced by H. pylori infection prior to gastric cancer was investigated. The transformation was then compared between Indonesian and Japanese patients, the two countries that represent the “Asian paradox”.

From 1998 to 1999, 42 Japanese patients at Yamanashi Medical University Hospital, Koufu and 125 Indonesian patients at Metropolitan Medical Centre Hospital, Jakarta were consecutively enrolled. From this research, it was seen that there was a significant difference in the grade and activity of gastric mucosal changes between Indonesian and Japanese H. pylori-positive patients. This finding suggests that there may be a different host response between Indonesian and Japanese people regarding H. pylori infection. The authors believe that lifestyle and genetic factors are considered to play a major role, in the meantime, their research may act as the initial step in explaining the “Asian paradox”.

Reference: Abdullah M, Ohtsuka H, Rani AA, Sato T, Syam AF, Fujino MA. Helicobacter pylori infection and gastropathy: A comparison between Indonesian and Japanese patients. World J Gastroenterol 2009; 15(39): 4928-4931 http://www.wjgnet.com/1007-9327/15/4928.asp

Source: Jin-Lei Wang

World Journal of Gastroenterology

• Explain to interested patients that these results indicate that the risk of dying from cancer has steadily declined since the middle of the last century.

Although the incidence of cancer hasn’t changed much, the mortality rate for all types of the disease peaked in the middle of the 20th century and has retreated steadily since then, researchers found.

Among individuals born in 1925 or later, the decline in cancer mortality has been more pronounced in the youngest age groups than in the older ones (drop of 25.6% versus 6.8% per decade), according to Eric Kort, MD, of Van Andel Research Institute in Grand Rapids, Mich., and colleagues.

“Whereas there are likely other contributory factors, this analysis suggests that efforts in prevention, early detection, and/or treatment have significantly affected our society’s experience of cancer risk,” the researchers said.

They reported their findings in the Aug. 15 issue of Cancer Research.

The researchers examined cancer mortality rates broken down by both age and birth cohort (10-year intervals), which they said improves detection of trends.

“The conventional practice of analyzing overall age-adjusted cancer mortality rates heavily emphasizes the experience of older, higher-mortality age groups,” they said. “This may conceal shifts in lifetime cancer mortality experience emerging first in younger age groups.”

So, using mortality data from 1955 to 2004 from the World Health Organization’s Statistical Information System, they tracked the burden of cancer death in individuals born as early as 1875.

Rates of cancer death peaked in individuals born from 1915 through 1924, and declined thereafter.

Beginning with the birth cohort of 1925 through 1934, each subsequent cohort had a lower lifetime risk of dying from cancer for almost all age comparisons. The trend held true for both males and females.

There were two exceptions. The cancer mortality rate for 10- to 14-year-olds born in 1935 was the same as that for children of similar ages born in 1945. The rate was also equal in 5- to 9-year-olds born in 1985 and 1995.

The declining cancer mortality rate cannot be attributed to decreasing cancer incidence, the researchers said. In fact, with the exception of lung cancer, the incidence of most cancer types has remained relatively stable.

“Rather,” they explained, “the net improvement in cancer mortality in birth cohorts born since 1925 seems to reflect a succession of public health and medical care efforts.”

The analysis of cancer mortality rates by age group and birth cohort allows for a interpretation of mortality trends that differs from conventional analyses, the researchers said.

“The canonical interpretation of age-adjusted, all-site cancer mortality data is that mortality rates were rising through most of the 20th century and only began to decline slightly in the mid-1990s,” they said.

But the current findings indicate that “our efforts against cancer, including prevention, early detection, and better treatment, have resulted in profound gains,” Kort said. “But these gains are often unappreciated by the public due to the way the data are usually reported.”

The researchers acknowledged that the study was limited by the recording of death events that is subject to changes in coding, legislative requirements, and recording habits.