. Step 27 of 40
Clinical Stem 2
A patient with pulmonary nodules 1 year after curative intent resection of primary lung adenocarcinoma

Answer D
Performing VATS to obtain more tissue or initiating chemotherapy while waiting for results from the current biopsy in this patient is counter-intuitive. Because EGFR status in primary and metastatic tumors may not be identical, however, EGFR status in the primary tumor may not predict EGFR status in metastases or sites of disease recurrence.

ALK gene rearrangements are currently detectable using IHC, FISH, or reverse-transcriptase polymerase chain reaction, also known as RT-PCR. In the United States, as of June 2013, the only FDA-approved test for detection of ALK rearrangements is the FISH test.

Molecular testing on resected stage I-III lung cancer specimens allows for enrollment in clinical trials that target mutation-specific, directed therapy and assists with therapy selection for recurrent disease when it occurs. Resected surgical specimens are the gold standard against which small volume histology or cytology specimens are measured for adequacy, both for histologic diagnosis of cancer and molecular testing. Resected tissue may be available, however, in only that subset of patients with NSCLC who undergo surgical resection with curative intent.

While the most recent available tissue is preferred for molecular analysis there is no strong evidence to justify procedures solely to procure tissue from a metastasis prior to initiation of TKI therapy if an earlier primary lesion is available and suitable for analysis, unless there is strong suspicion of its origin from a separate primary.
Guidelines from the College of American Pathologists state that in the absence of previous or current therapy with a target inhibitor, primary tumors and metastatic lesions are equally suitable for testing.

The choice of which sample to test should be based mainly on the sample's quality characteristics such as tumor content and preservation, rather than on whether it is from a primary or metastatic lesion.

Click here to download supplement materials

References:
  1. Thunnissen E, Bubendorf L, Dietel M, et al. EML4-ALK testing in Non small cell carcinomas of the lung: A review with recommendations.Virchows Arch 2012;461: 245-257.
  2. D'Angelo SP, Park B, Azzoli CG, et al. Reflex testing of resected stage I through III lung adenocarcinomas for EGFR and KRAS mutation: report on initial experience and clinical utility at a single center. J Thorac Cardiovasc Surg. 2011; 141: 476-80
  3. Marks JL, Broderick S, Zhou Q, et al. Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma. J Thorac Oncol. 2008;3:111-6
  4. Monaco SE, Nikiforova MN, Cieply K, et al. A comparison of EGFR and KRAS status in primary lung carcinoma and matched metastases. Hum Pathol. 2010;41:94-102.
  5. Kalikaki A, Koutsopoulos A, Trypaki M, et al. Comparison of EGFR and KRAS gene status between primary tumours and corresponding metastases in NSCLC. Br J Cancer. 2008;99:923?929.
  6. Gallegos Ruiz MI, van Cruijsen H, Smit EF, et al. Genetic heterogeneity in patients with multiple neoplastic lung lesions: a report of three cases. J Thorac Oncol. 2007;2:12?21.
  7. College of American Pathologists, International Association for the Study of Lung Cancer, Association for Molecular Pathology. Lung cancer biomarkers guideline draft recommendations. lung_public_comment supporting_materials.pdf. Published 2011. Accessed July 29, 2012.