Attempting to identify molecular markers of primary gastric B-cell lymphoma, researchers in China found that so-called double-hit lymphoma is rare in these patients, while a double-protein appearance of tumors predicts a poor prognosis.
The study, “Clinical Significance of ‘Double-hit’ and ‘Double-protein’ expression in Primary Gastric B-cell Lymphomas,“ published in the Journal of Cancer, also identified molecular characteristics linked to better outcomes, suggesting the findings can be used to guide physicians in making treatment choices and predict outcomes.
Although primary gastric lymphoma is the second most common cancer of the stomach, researchers are still unsure about how the two forms — a slow-growing type called MALT, or the more aggressive diffuse large B-cell lymphoma (DLBCL) — relate to each other.
There are also no recommendations of treatment and physicians find it difficult to accurately predict how patients will react to treatment and what their long-term survival odds look like.
This uncertainty has spurred research into the molecular features of lymphoma, with scientists hoping to find measurable factors linked to treatment response or prognosis. Finding such molecular tags has led to the establishment of two key terms: double-hit and double-protein lymphomas.
A double-hit lymphoma is basically a tumor harboring two mutations in key genes, instead of the more usual one. This combination, affecting the genes Myc and bcl2 or bcl6, is particularly challenging, since Myc is a factor preventing rampant cell growth, and the blc genes protect from cell death.
Mutations in these genes, overcoming these important functions, give a cancer two mechanisms by which it can grow uncontrollably, and the presence of the resulting proteins in the tumor tissue, MYC, BCL2, and BCL6 is referred to as double-protein.
It may seem confusing, but double-protein lymphomas can exist without any accompanying mutations, and synthesis of the proteins are, in such cases, triggered by other factors.
Analyzing tissue from 188 patients diagnosed with gastric B-cell lymphoma, researchers at the Changhai Hospital and The Second Military Medical University in China did not find any case of double-hit lymphoma in this group, although mutations in one of the three genes affected 45 percent of the patients.
Despite this, the team found 12 cases with double-protein appearance. These patients had a significantly lower survival time compared to patients having high levels of one or none of the proteins.
Patients who did not have increased levels of any of the three proteins had a much better prognosis, regardless of the stage and type of their gastric cancer and which treatment they received. The team also found two other molecular markers linked to a better prognosis.
“These results would be of importance for clinical stratified management and precision medicine of gastric B-cell lymphomas,” the authors wrote in their report.