Approximately 80% of all pulmonary malignancies in the United States are non-small cell lung carcinoma (NSCLC), with about 170,000 new cases diagnosed each year. NSCLC is divided into three major tumor types: (i) adenocarcinoma, which accounts for approximately 40% of all cases and is the predominant tumor type that arises in non-smokers; (ii) squamous cell carcinoma, which accounts for 30% of all lung cancers; and (iii) large cell carcinoma or undifferentiated tumors, which are difficult to classify.
While classifying a NSCLC into histotype can be relatively straight forward in patients whose tumors have been surgically resected (primarily early stage patients), diagnosis in later stage patients can be much more difficult. Typically in metastatic disease, biopsies are obtained by the use of needle biopsy or bronchial brushings where the sample is small and/or disrupted. Error rates may be as high as 25% when comparing diagnosis on needle biopsy to subsequent surgical specimens. Pulmotype is designed to help pathologists distinguish histotype when insufficient tumor sample is available for morphologic classification, or as an aid to distinguishing undifferentiated or difficult to classify cases on larger specimens.
Although pathologists have traditionally used biomarkers to help differentiate tumor type, there is currently no widely accepted, clinically validated, molecular-based tool to help distinguish the different histological types. Prior to the advent of targeted therapy, classification had little clinical use. However, newly developed targeted therapies show different clinical effectiveness or toxicity dependent upon the histotype of the tumor. Epidermal growth factor receptor (EGFR) inhibitors have been shown to be more effective in adenocarcinoma patients who were previously treated with chemotherapy and non-smokers. Drugs targeting the vascular endothelial growth factor (VEGF) have been shown to improve overall survival in NSCLC patients when combined with first line of chemotherapy or EGFR targeted therapy. However, because of adverse hemorrhagic events in patients with squamous cell carcinoma, this drug is recommended by the manufacturer only for use in non-squamous cell patients. The development of therapies that are more effective or less toxic when used in the appropriate NSCLC subtype mandates obtaining an accurate diagnosis.
Pulmotype is an easy to use, inexpensive assay using traditional IHC technology that can aid a pathologist in histologic diagnosis and, having determined the appropriate tumor type, direct the oncologist to the most appropriate course of therapy.