Anti-SOX2 Antibodies May Be Useful Markers of Small Cell Lung Cancer in LEMS Patients, Study Says

Antibodies that recognize a protein called SOX2 that are specific markers of small cell lung cancer (SCLC) could be used to identify patients with Lambert-Eaton myasthenic syndrome (LEMS) who have this type of cancer, a study reports.

The study, “The utility of anti-SOX2 antibodies for cancer prediction in patients with paraneoplastic neurological disorders,” was published in the Journal of Neuroimmunology.

While 40-50 percent of cases of LEMS are of unknown cause, in about 50-60 percent of patients, the disease is associated with another underlying disease, particularly SCLC.

In these cases, it is thought that the immune system’s fight against the cancer ends up attacking the connections between nerve ends and muscle fibers, because the immune system may recognize some proteins shared by cancer cells and nerve endings.

These types of conditions, in which distant tumor effects result in a neurological presentation, are called paraneoplastic neurological disorders (PNDs).

Several studies have suggested that antibodies that recognize the SOX2 protein may be useful in predicting with high specificity the presence of SCLC, including in patients with symptoms of LEMS.

However, some patients who have neurological symptoms resembling a paraneoplastic neurological disorder do not actually have a tumor.

Therefore, an international team, led by researchers at the Queen’s Medical Centre in the U.K., conducted a study to determine whether anti-SOX2 antibodies could be used to identify SCLC cancer in patients with paraneoplastic and neurological signs.

Another goal of their study was to see if anti-SOX2 antibodies could also be markers for other cancer types commonly associated with paraneoplastic neurological disorders, such as thymoma (tumor of the thymus), teratoma, breast or ovarian cancer.

For this purpose, researchers quantified the amount of anti-SOX2 antibodies in the blood of 313 patients who had the following neurological symptoms: LEMS (126 patients), paraneoplastic cerebellar degeneration (PCD; 20 patients), idiopathic late-onset cerebellar ataxia (20 patients), opsoclonus-myoclonus syndrome (OMS; 19 patients), NMDA-R-antibody associated encephalitis (18 patients), acetylcholine receptor antibody positive myasthenia gravis (45 patients), limbic encephalitis (LE; 20 patients), subacute sensory neuronopathy (SSN; 45 patients).

Among this population, some patients had SCLC tumors, non-SCLC lung tumors, or teratoma, among other tumor types.

For comparison, researchers also analyzed the blood of 676 individuals who had cancer but no neurological signs. As controls, they included 414 healthy individuals, without a current or prior history of cancer and no underlying neurological conditions.

In patients without neurological symptoms, SOX2 antibodies were found in 29.7% (77 of 259) of those who had an SCLC tumor. In comparison, these antibodies were much more rare in those with non-SCLC cancer (6%), ovarian cancer (4%), or even absent in those with breast cancer. In age-matched healthy controls, very few had the antibodies (1.9%).

Among those with LEMS, SOX2 antibodies were detectable in most patients who had SCLC (61%), as well as in a significant proportion of patients who had other types of PNDs associated with this type of cancer.

SOX2 antibody levels were similar between those who had LEMS or PCD associated with SCLC, but significantly higher than those who had OMS or SSC associated with SCLC.

These results agree with prior reports suggesting that SOX1 and SOX2 antibodies have been found in 64-78% of patients with SCLC and LEMS compared with only 0-5% of non-tumor LEMS patients.

“We have demonstrated that SOX2 antibodies are highly specific [over 90% specific] for the presence of SCLC in patients presenting with a range of PNDs,” the researchers wrote, explaining that these antibodies are rarely found in patients with other tumors, whether neurological symptoms are present or not.

Therefore, a positive test for anti-SOX2 antibodies in a patient with a PND, such as one with symptoms of LEMS, “is highly suggestive of an underlying SCLC,” they said.

“Antibodies to other tumour-associated antigens associated with other malignancies such as breast or ovarian cancer may be useful biomarkers at first presentation in similar PNDs,” the team concluded.