Cytokine Molecule Could Offer Prognostic Guidance in Lung NETs

A new study suggests that the cytokine CXCL12 could be useful as a prognostic biomarker in patients with neuroendocrine tumors of the lung (LNETs), and in particular, atypical carcinoids (ACs).

LNETs account for approximately one-quarter of all primary lung neoplasms. “The management of LNETs represents a clinical challenge given their diversity in clinical presentation and outcome,” wrote study authors led by Alessandro Del Gobbo, MD, of the Ospedale Maggiore Policlinico at the University of Milan in Italy. “No immunohistochemical (IHC) markers have been found to be reliable in predicting prognosis in ACs. In order to improve the clinical management of LNETs, additional tools to better stratify these patients are required.”

In the new retrospective analysis, the researchers used IHC on a cohort of 112 resected LNETs; these included 21 large-cell neuroendocrine carcinomas (LCNECs), 12 small-cell carcinomas (SCLCs), 46 typical carcinomas (TCs), and 33 ACs. Results of the study were published in Cellular Oncology.

In the full cohort, 16.1% were considered positive for CXCL12 expression; this included 8.7% of TCs, 15.1% of ACs, 38% of LCNECs, and 8.3% of SCLCs. When taken together, CXCL12-positive patients had shorter disease-free survival compared with negative cases, with a hazard ratio (HR) of 3.99 (95% CI, 0.91–17.35; P = .002). Specifically for patients with ACs, those who were CXCL12-positive had an HR for recurrence of 6.55 (95% CI, 0.90–47.37; P = .004). There was no correlation seen between expression of the biomarker and overall survival.

The Ki-67 proliferation index, which has also been put forward as a potential prognostic marker, was found to be higher in the CXCL12-positive patients than in those who were negative.

“Our findings provide evidence to suggest that the expression of this small cytokine may serve as a bona fide risk indicator of recurrences in ACs,” the authors concluded, calling this a “step forward” in the management of these malignancies.

Andrew E. Hendifar, MD, MPH, an expert on neuroendocrine tumors at Cedars-Sinai Medical Center in Los Angeles, who was not involved with the new research, agreed that the finding is important and told Cancer Network that it suggests that CXCL12 might play a role in LNET tumorigenesis. “Developing this marker for risk stratification could help identify patients at higher risk for disease progression or metastases,” he said.