Detection of chromosomal abnormalities associated with prognosis of non small cell lung cancer

Abstract

The methods and compositions described herein address the need for a diagnostic method that can be provided to patients with early stage lung cancer, especially non-small cell lung cancer (NSCLC), to determine whether the patient is at increased risk of poor disease outcome. The methods and compositions thus allow for more informed treatment decisions for the early stage lung cancer patient.

Description

CROSS REFERENCE TO A RELATED APPLICATION[0001]This application claims priority from U.S. provisional patent application Nos. 61 / 254,968 and 61 / 254,955, both filed on Oct. 26, 2009, the disclosures of which are herein incorporated by reference in their entireties.FIELD OF THE INVENTION[0002]The present disclosure relates to in vitro diagnostic assays of tissue samples from lung cancer patients for determining patient prognosis, and in particular relates to an in vitro assay for determining prognosis of early stage patients, such as those diagnosed with Stage I or Stage II non-small cell lung cancer.BACKGROUND OF THE INVENTION[0003]Lung cancer accounted for almost one third of cancer deaths in the United States in 2005, and is broadly classified into two types: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer (NSCLC) comprises 80-85% of lung cancer cases in the United States. NSCLC comprises three major types: (i) Squamous cell carcinoma, which begins ...

AI Technical Summary

Problems solved by technology

Early-stage NSCLC patients are almost always treated by surgical resection seeking complete tumor removal, yet a significant risk of recurrence exists for these early stage patients even where the tumor is believed to be completely resected.

Current diagnostic modalities do not permit accurate prediction of which of these early stage cancers are high risk for recurrence and thus should be treated post-resection with adjuvant chemotherapy or before the resection using neoadjuvant chemotherapy.

However, such probes are not as accurate at enumerating chromosomes since the loss of signals for such probes may not always indicate a loss of the entire chromosomes.

These loci also include regions of chromosomal DNA, the deletion of which produces a copy number loss at the locus, wherein the copy number loss is associated with a poor disease outcome.

A test with high sensitivity has few false negative results, while a test with low sensitivity has many false negative results.

Additionally, in some embodiments, the number of probes within a set that is to be viewed by a human observer (and not with computer assisted imaging techniques) may be restricted for practical reasons, e.g., by the number of unique fluorophores that provide visually distinguishable signals upon hybridization.

However, the increases in sensitivity become smaller and smaller with the addition of more probes and at some point the inclusion of additional probes to a probe combination is not associated with significant increases in the sensitivity of the assay (“diminishing returns”).

Increasing the number of probes in a probe combination may decrease the specificity of the assay.

Thus, each probe in a probe combination complements the other(s), i.e., identifies increased risk of poor disease outcome in NSCLC where the other probes in the combination sometime fail to identify.

However, chromosomal losses sometimes occur as an artifact in normal cells because of random signal overlap and / or poor hybridization.

In sections of formalin-fixed paraffin-embedded material, commonly used to assess biopsies, truncation of nuclei in the sectioning process can also produce artifactual loss of chromosomal material.

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