Molecular testing in lung cancer: fine-needle aspiration specimen adequacy and test prioritization prior to the CAP/IASLC/AMP Molecular Testing Guideline publication.
BACKGROUND
Subtyping of lung carcinoma with immunohistochemistry is essential for diagnosis, whereas molecular testing (MT) is required for therapy guidance. In the current study, the authors report on MT performed on fine-needle aspiration specimens at the study institution over a 2-year period preceding the April 2013 College of American Pathologists (CAP)/International Association for the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP) Molecular Testing Guideline (MTG) publication.


METHODS
The database of the study institution was retrospectively queried for cases of lung and thoracic/lower cervical lymph node fine-needle aspiration specimens for 2011 through 2012.


RESULTS
Of 246 selected cases, 26 featured a limited amount of material in cell blocks. MT increased significantly between 2011 and 2012 and was requested in 39.4% of cases (97 of 246 cases): 86 of those cases had at least 1 MT result and 11 had insufficient material for any MT. Anaplastic lymphoma kinase (ALK) testing was performed in 9 cases in which DNA was insufficient for epidermal growth factor receptor (EGFR) testing. In addition, 13 cases of adenocarcinoma/non-small cell lung carcinoma had at least 1 MT canceled because of insufficient DNA, but at the same time had an average of 3.46 immunohistochemical stains performed.


CONCLUSIONS
Of all the cytology specimens, 10.6% featured limited material; however, no universally accepted testing sequence priority was available at the time the study was performed. As per the MTG, MT should take precedence over immunohistochemistry in cases of adenocarcinoma/non-small cell lung carcinoma. Approximately 5.3% of the specimens in the current study had insufficient material for MT while having multiple stains performed instead. The MTG also recommend performing EGFR before ALK testing; the authors found 9 cases with insufficient material for EGFR testing that had ALK testing performed. The results of the current study underscore the need for a testing prioritization algorithm in view of the MTG publication to serve as reference for both clinicians and pathologists.
Department of Pathology, North Shore LIJ - Lenox Hill Hospital, New York, New York.
Oana C
OC
Rafael
Mohamed
M
Aziz
Harry
H
Raftopoulos
Oana E
OE
Vele
Weisheng
W
Xu
Chiara
C
Sugrue
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077548:Anaplastic Lymphoma Kinase; D044963:Biopsy, Fine-Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D003581:Cytodiagnosis; D066246:ErbB Receptors / Q000235:genetics; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D025202:Molecular Diagnostic Techniques / Q000592:standards*; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D017410:Practice Guidelines as Topic / Q000592:standards*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011643:Publishing; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D012955:Societies, Medical; D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; C000626175:Alk protein, rat; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
Kirsten rat sarcoma viral oncogene homolog (KRAS); algorithm; anaplastic lymphoma kinase (ALK); epidermal growth factor receptor (EGFR); guideline; lung cancer; molecular testing