CD44-positive cancer stem-like cells may signal poor survival in gastric cancer

Last Updated: 2016-12-20

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - In gastric cancer, the presence of CD44-positive cancer stem-like cells at the invasive tumor front (ITF) indicates poor survival, according to new research.

"The observation confirms the role of these cells in defining the biologic behavior of the tumor," said Dr. Bassel El-Rayes, director of the gastrointestinal oncology program at Winship Cancer Institute of Emory University in Atlanta, Georgia, who was not involved in the study.

"This paper helps clinicians realize the complexity of the disease and understand why their patients with tumors similar in type, size, and stage can have such variable outcomes," he told Reuters Health by email.

In the study, online December 8 in the British Journal of Cancer, Dr. Satoshi Murata of Shiga University of Medical Science in Otsu, Japan, and colleagues examined resected primary gastric cancers from 123 patients ages 38 to 91.

Using CD44 as a marker of cancer stem cells (CSCs), the researchers examined CD44 standard (CD44s), CD44 variant-6 (CD44v6), and CD44 variant-9 (CD44v9) expression in the resected primary tumors.

Eleven percent of tumors were CD44s-positive, 64% were CD44v6-positive, and 38% were CD44v9-positive. Patients with CD44-positive expression at the ITF had significantly shorter disease-specific survival than patients with negative expression.

"The all-positive group showed the worst survival, that is, a 51.9% 5-year survival rate; the double-positive and single-positive groups showed 73.7% and 90.8% 5-year survival rates, respectively, and the all-negative group showed the best 5-year survival rate, that is, 97.4%," the researchers write.

"Previously published papers show that higher CSCs in tumors lead to a more aggressive course. This paper confirms those findings and sheds light on the impact of having CSCs at the invasive tumor border," Dr. El-Rayes said.

"The presence of CSCs at the edge of the tumor may be a prognostic factor that can be used to risk stratify patients and decide who needs additional therapy after surgical resection. Developing drugs that target CSCs may be an approach to prevent spread and improve outcomes of early-stage gastric cancer," he added.

Dr. Dean G. Tang, professor of oncology and chair of the Department of Pharmacology and Therapeutics at Roswell Park Cancer Institute in Buffalo, New York, said the study is the first to link "CD44 expression at the ITF with poor survival of gastric cancer patients."

"What's unknown is whether these CD44-expressing gastric cancer cells observed at the ITF are truly more invasive and metastatic. Prospective experiments using purified cells should be performed to address the critical question," Dr. Tang, who was not involved in the study, told Reuters Health by email.

He noted that the study's main strength is its use of clinical patient samples, while its major weakness is the use of "dead" archive tissues.

"Cancer stem cells are clinically relevant cancer cell populations and their location and abundance often indicate how aggressive and therapy-responsive patient tumors may be," he said. "On the other hand, prospective LIVE experiments are generally needed to answer the question of whether the marker-positive cells truly possess cancer stem cell properties."

Dr. Murata did not respond to requests for comments.

SOURCE: http://bit.ly/2hV8NBu

Br J Cancer 2016.