Purpose: To evaluate the frequency of molecular testing in pulmonary carcinomas.
Background: Pulmonary carcinoma represents the second most common type of new malignancies in males and females. Although its incidence is plateauing, it represents the most common cause of cancer-related death in both genders. The 5-year survival rate is only 18%. The main risk factor in both genders is smoking. Carcinogenesis and tumor progression in some tumors involve mutations in relevant genes that further cell survival and proliferation and provide advantage over neighboring cells. Although therapy has traditionally been guided by tumor histology, drugs have been developed that specifically target driver mutation metabolic pathways. These drugs promise higher efficacy and lower toxicity; however, their use must be guided by the genetic makeup of individual tumors. One such mutation occurs in the EGFR gene and is more common in women with no smoking history. Another, mutually exclusive mutation consists of rearrangements in the ALK gene. These alterations render the cells sensitive to targeted therapy with tyrosine kinase inhibitors.
Data Analysis/Results: At the Minneapolis VA Medical Center, these tests are performed when ordered by the oncologists. We analyzed the frequency of mutations in exons 18-21 of the EGFR gene by PCR-based essay and ALK rearrangements by FISH technique in lung carcinomas. One hundred eighty-three biopsy and cytology specimens collected between January 2009 and June 2015 were evaluated. Of these, 11 (6%) were positive for EGFR mutations; none was positive for ALK rearrangements. All positive cases were morphologically adenocarcinomas; pulmonary origin was supported by clinical, radiologic and immunohistochemical criteria (positivity for cytokeratin 7 and for TTF-1). Specimens consisted of cell blocks (pleural effusion, fine needle aspirates) and needle biopsy cores of primary tumors or metastases or lobectomy specimen.
Implications: Compared with the literature, our frequency of mutant cases for the 2 targets analyzed is lower. This may be due to the fact that our patient population consisted predominantly of men with a history of smoking. It is important to analyze local statistics and compare them with the VA systemwide data for establishing guidelines and cost analysis.
