A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry.

Abstract

PURPOSE:

Approximately 5% of lung adenocarcinomas harbor an EML4-ALK gene fusion and define a unique tumor group that may be responsive to targeted therapy. However ALK-rearranged lung adenocarcinomas are difficult to detect by either standard fluorescence in situ hybridization or immunohistochemistry (IHC) assays. In the present study, we used novel antibodies to compare ALK protein expression in genetically defined lung cancers and anaplastic large cell lymphomas.

EXPERIMENTAL DESIGN:

We analyzed 174 tumors with one standard and two novel monoclonal antibodies recognizing the ALK protein. Immunostained tissue sections were assessed for the level of tumor-specific ALK expression by objective quantitative image analysis and independently by three pathologists.

RESULTS:

ALK protein is invariably and exclusively expressed in ALK-rearranged lung adenocarcinomas but at much lower levels than in the prototypic ALK-rearranged tumor, anaplastic large cell lymphoma, and as a result, is often not detected by conventional IHC. We further validate a novel IHC that shows excellent sensitivity and specificity (100% and 99%, respectively) for the detection of ALK-rearranged lung adenocarcinomas in biopsy specimens, with excellent interobserver agreement between pathologists (kappa statistic, 0.94).

CONCLUSIONS:

Low levels of ALK protein expression is a characteristic feature of ALK-rearranged lung adenocarcinomas. However, a novel, highly sensitive IHC assay reliably detects lung adenocarcinomas with ALK rearrangements and obviates the need for fluorescence in situ hybridization analysis for the majority of cases, and therefore could be routinely applicable in clinical practice to detect lung cancers that may be responsive to ALK inhibitors.

• Authors: Mari Mino-Kenudson, Lucian R Chirieac, Kenny Law, Jason L Hornick, Neal Lindeman, Eugene J Mark, David W Cohen, Bruce E Johnson, Pasi A Jänne, A John Iafrate, Scott J Rodig
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 5 Pg. 1561-71 (Mar 01 2010) ISSN: 1557-3265 [Electronic] United States
• PMID: 20179225 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal
• EML4-ALK fusion protein, human
• Oncogene Proteins, Fusion

Topics

• Adenocarcinoma (genetics, metabolism)
• Antibodies, Monoclonal
• Humans
• Image Interpretation, Computer-Assisted
• Immunohistochemistry (methods)
• In Situ Hybridization, Fluorescence
• Lung Neoplasms (genetics, metabolism)
• Observer Variation
• Oncogene Proteins, Fusion (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sensitivity and Specificity