Pulmotype is a five antibody immunohistochemistry (IHC) test developed by Applied Genomics that can be used to aid in the histological distinction between adenocarcinoma and squamous cell carcinoma in non-small cell lung cancer (NSCLC) tumor specimens. This distinction has recently become clinically significant because the choice of targeted therapy hinges in part upon this pathological diagnosis.

Approximately 80% of all pulmonary malignancies in the United States are NSCLC with about 170,000 newly diagnosed cases each year. NSCLC is histologically divided into three tumor types: (i) adenocarcinoma, which accounts for approximately 40% of all NSCLC cases and is the predominant tumor type arising in non-smokers; (ii) squamous cell carcinoma which accounts for 30% of all lung cancers; and (iii) large cell carcinoma.

While classifying a NSCLC into the appropriate histotype can be relatively straight forward in patients whose tumors have been surgically resected (primarily early stage patients), a pathological diagnosis in later stage patients can be much more difficult if the biopsy sample is small and/or disrupted such as those samples obtained by core or needle biopsy.

The histologic classification of non-small cell lung tumors has gained clinical relevance because newly developed targeted therapies show different clinical effectiveness or toxicity dependent upon the histotype of the tumor. Epidermal growth factor receptor (EGFR) inhibitors such as gefitinib (Iressa®) and erlotinib (Tarceva®) have been shown to be more effective in certain subgroups of patients including adenocarcinoma patients who were previously treated with chemotherapy and non-smokers.^1,2 Bevacizumab (Avastin®), targeted to vascular endothelial growth factor has been shown to improve overall survival in NSCLC patients when combined with a first line of chemotherapy or erlotinib.^3,4 However, these studies also demonstrated that squamous cell patients had many more incidents of severe or fatal pulmonary hemorrhage (31%) versus the number of these events in patients with NSCLC excluding predominantly squamous histology (2.3%). These extreme hemorrhagic events have resulted in the manufacturer of Avastin and others recommending the use of Avastin in only in non-squamous cell patients and subsequent clinical trials with Avastin have only included patients with non-squamous histological subtypes.

Thus, the development of therapies that are more effective or less toxic when targeted to one particular subtype of NSCLC mandates obtaining an accurate subtype diagnosis. Pulmotype is an easy to use, inexpensive assay using traditional IHC technology familiar to the pathologist that can aid the pathologist in diagnosis and, having determined the appropriate histotype, direct the oncologist to the most appropriate course of therapy.

References:

1. Shepherd FA et al. Erlotinib in previously treated non-small cell lung cancer. N Engl J Med 2005; 353:123-32.
2. Miller VA et al. Bronchioalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced small cell lung cancer. J Clin Oncol 2004; 22:1103-1109.
3. Herbst RS et al. Phrase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody Becacizumab in combination with the HER-1/Epidermal growth factor receptor   tyroszine kindase inhibitor Erlotinib for patients with recurrent non-small cell lung cancer. J Clin Oncol 2005; 23: 2544-55.
4. Tyagi P. Bevacizumab, when added to paclitaxel/carboplatin, prolongs survival in previously untreated patients wth advanced non-small cell lung cancer: preliminary results from the ECOG 4599 trial.  Clin Lung Cancer 2005; 6:276-278.