Clinical Question:
Is Methlylation assay of bronchial aspirates useful to diagnose lung cancer?
Bottom Line:
Findings suggest that the QMSP assay could be applied as a reflex test in
cases of suspected lung cancer that defy a definite diagnosis by
conventional methods. Thus, the assay could be a useful diagnostic adjunct
especially regarding peripheral tumors.
Reference:
Methylation assay for the diagnosis of lung cancer on bronchial aspirates: a
cohort study.Schmiemann V, Bocking A, Kazimirek M, Onofre AS, Gabbert HE,
Kappes R, Gerharz CD, Grote HJ.Clin Cancer Res. 2005 Nov 1;11(21):7728-34.
Study Design:
Cohort Study (retrospective)
Synopsis:
Recent studies have detected aberrant promoter methylation of adenomatous
polyposis coli promoter 1 A (APC), cyclin-dependent kinase inhibitor-2A
(p16(INK4a)), retinoic acid receptor beta2, and RAS association domain
family protein 1 (RASSF1A) in bronchial aspirates and suggested their use as
biomarkers for lung cancer diagnostics. The purpose of this study was to
validate these candidate marker genes in a retrospective cohort
study.Bronchial aspirates collected from a cohort comprising 247 patients
with suspected lung cancer were investigated retrospectively regarding
aberrant promoter methylation using a quantitative methylation-specific
real-time PCR (QMSP).Eighty-nine patients were diagnosed with primary lung
cancer, 102 had benign lung disease, and 56 showed miscellaneous other
conditions. A panel consisting of APC, p16(INK4a), and RASSF1A emerged as
useful combination. This panel detected aberrant methylation in bronchial
aspirates of 22 of 35 (63%) and 21 of 44 (44%) centrally and peripherally
located primary lung cancers, respectively. Bronchial aspirates also showed
aberrant methylation in 5 of 7 (71%) patients with a recurrent lung cancer
and in 8 of 30 (27%) cases without tumor recurrence. In contrast, only 1 of
102 patients with benign lung disease displayed a (false) positive test
result. Rarely, aberrant methylation was found in patients with other
malignancies (3 of 16). The QMSP assay correctly confirmed lung cancer in 8
of 12 (67%) cases with an ambiguous cytology. Moreover, it disclosed 9 of 26
(35%) of peripheral tumors lacking simultaneous cytologic or histologic
diagnosis of malignancy.
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