Are anaplastic lymphoma kinase (ALK) and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation driver biomarkers of pulmonary neuroendocrine tumors (NETs) and carcinomas (NECs)?
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Birgitta Hiddinga1, Karen Zwaenepoel2, Annelies Janssens3, Jan Van Meerbeeck3 and Patrick Pauwels2
1 Department of Pulmonary Diseases, University Medical Center Groningen, Groningen, The Netherlands
2 Department of Pathology, Antwerp University Hospital, Edegem, Belgium
3 Department of Pulmonology and Thoracic Oncology, European Reference Network for Rare or Low Prevalence Lung Diseases: ERN-LUNG, Antwerp University Hospital, University of Antwerp, Edegem, Belgium
Keywords: MGMT promoter methylation; anaplastic lymphoma kinase; neuroendocrine tumor; neuroendocrine carcinoma; small cell lung cancer
Received: December 24, 2021 Accepted: May 07, 2022 Published: June 01, 2022
Background: Novel targets in neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are needed to improve outcome. The presence of O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation in NETs and NECs may act as a predictive marker for response on treatment with temozolomide. As anaplastic lymphoma kinase (ALK) plays an important role in the nervous system we hypothesized that ALK rearrangement can act as a biomarker in patients with NETs and NECs.
Materials and Methods: We performed a retrospective analysis to establish the frequency of MGMT promoter methylation and ALK expression in tissue samples of patients with NETs and NECs.
Results: 21% (14/67) of patients tested positive for MGMT promoter methylation. MGMT promoter methylation was present in 33% (3/9) patients with typical carcinoid, in 22% (2/9) patients with atypical carcinoid, in 22% (8/37) patients with small cell lung cancer and in 8% (1/12) patient with large cell neuroendocrine carcinoma. ALK- expression was present in 14% (10 of 70 patients). In all of these patients, no ALK-rearrangement nor ALK-mutation was revealed.
Conclusions: Routine testing of NET and NEC samples for an ALK rearrangement is not recommended as ALK-expression is not associated with an ALK-rearrangement. Routine testing of NET and NEC samples for MGMT will detect a promoter hypermethylation in a sizable minority of patients who are eligible for a targeted treatment with temozolomide.
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