Molecular Versus Histopathologic Staging of Lung Adenocarcinoma with Multiple Tumor Nodules
Nike T Beaubier, Mahesh M Mansukhani, Alain C Borczuk. Columbia University Medical Center, New York, NY
Background: The AJCC 7th edition staging of lung adenocarcinoma incorporated changes in the staging of multiple tumor nodules. For instance, two separate primary tumors in the same lobe would be staged as T1, while a primary tumor and metastatic lesion in the same lobe would be staged as T3. These decisions are based on histologic similarity. Changes in staging result in different predictions of prognosis and impact therapy. Currently there is no accepted gold standard for determining clonality for staging purposes and determinations are made based on histologic appearance of the tumor. As molecular subtyping, particularly epidermal growth factor receptor (EGFR) and Kirsten-rat sarcoma 2 viral oncogene homolog (KRAS) mutation status becomes more prevalent, this information could be used to more accurately stage adenocarcinoma patients with multiple nodules.
Design: All lung adenocarcinoma cases from CUMC pathology with two or more synchronous or metachronous lesions which also had EGFR and KRAS mutation testing (direct sequencing and ARMS assay) (n = 24) were selected for review. The original reported tumor stage and molecular findings were noted, then tumors were blindly reviewed and scored by percentage of histologic subtype. Staging was done based on the highest percentage histologic subtype, secondary or unusual histologic pattern, and based on mutation analysis. Two cases, which were negative for all mutations tested, were deemed inconclusive by molecular staging and not used in the analysis.
Results: Staging results for original pathologic stage versus molecular stage are 71% (15/21 cases) concordant, primary histologic subtype versus molecular 64% (14/22 cases) concordant, and secondary or unusual histologic pattern versus molecular also 64% (14/22 cases) concordant. Interestingly, the same eight cases were not discordant in both analyses. There is only a 75% (18/24 cases) concordance rate between the two histologic methods.
Conclusions: EGFR and KRAS mutations are activating oncogenic mutations, and therefore early events in tumorigenesis. Thus, they are likely to be effective markers of clonality. In our series, staging by mutation analysis differed from the two histologic staging methods in 36% of cases. Adding molecular staging information to current histologic staging could increase the accuracy in patients with multiple separate tumors thereby improving therapeutic decision making.
Monday, March 19, 2012 1:30 PM
Platform Session: Section D, Monday Afternoon