Clinicopathological Features of NSCLC Patients Associated With the Chromosome 2p (EML4-ALK) (ALK)

CLINICOPATHOLOGICAL FEATURES OF NON-SMALL CELL LUNG CANCER PATIENTS ASSOCIATED WITH THE CHOROMOSOME 2p (EML4-ALK) INVERSION IN MEXICAN POPULATION.

Because ALK-positive lung cancer constitutes less than 5% of all lung cancers, it is critically important to select those patients who are more likely to have the ALK mutation. Clinical characteristics of patients with mutations in the target gene should also be known, so that the incidence of a given target mutation is established in a specific population. There is not incidence known in Mexican population, but it is believed it is greater.

Study Overview

• Status: Completed
• Conditions: Non Small-cell Lung Cancer

Detailed Description

Lung adenocarcinoma studies. The only inclusion criterion was the availability of tissue for biomarker studies. To identify ALK rearrangements, fluorescence in situ hybridization (FISH) studies were performed on 3 to 4 mm thick paraffin sections from NSCLCs. The commercially labeled Vysis LSI ALK Dual Color (split-apart), break-apart rearrangement probe (Abbott Molecular, Abbott Park, IL) was used to detect any rearrangement involving the ALK gene. The probe hybridizes to band 2p23, on either side of the ALK gene breakpoint. Criteria for probe signal interpretation in at least 200 interphase nuclei were as follow: 1) separated green and orange signals or single red signals identified cells with rearranged ALK; 2) overlapping of red and green signals (yellowish) indicated cells in which ALK was not rearranged.

FISH-positive samples for ALK rearrangement were defined as having cells with a clearly separated pair of probe signals, or with >15% of cells having loss of the 5´(centromeric) probe. The higher threshold for loss is necessary because parts of probes can be lost during sectioning.

The aim of our study is to evaluate the utility of IHC with 5A4 and RT-qPCR in the detection of ALK rearrangements in NSCLC compared with the current method of choice, FISH. Further, we report on the demographics, and clinicopathologic features of ALK-rearranged NSCLC in a Latin-American population.

Clinical details of these patients were included in a database. Further results will be analyzed with the program SPSS17

• Study Type: Observational
• Enrollment (Actual): 230

Contacts and Locations

Study Locations

• Mexico
  • DF
    • Mexico, DF, Mexico, 14080
      • Instituto Nacional de Cancerologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Mexican pupulation, with Non small-cell lung cancer.

Description

Inclusion Criteria:

• The only inclusion criterion was the availability of tissue for biomarker studies.

Exclusion Criteria:

• Disease Progression

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

ALK-BREAK APART; We reviewed 230 consecutive cases of NSCLC that were retrieved from oncologic molecular laboratory and diagnostic pathology unit at the Instituto Nacional de Cancerologia, Mexico city, between 2011 and 2014. Samples were sent to the unit of pathological anatomy, a Pathologist confirmed the histologic diagnosis. The only inclusion criterion was the availability of tissue for biomarker studies. Clinical and pathologic details of these patients were included in a database, obtained from medical records. For ALK fusion testing, we applied dual-color, break-apart FISH, RT-qPCR, and immunohistochemistry. Interpretation of the results was done in double-blind manner without knowing the results by other methods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FISH, IHC, RT-qPCR Comparison	200 samples underwent FISH, from them 63 underwent IHC and 48 RT-qPCR.	TWO YEARS

Collaborators and Investigators

• Sponsor: Instituto Nacional de Cancerologia de Mexico

Publications and helpful links

General Publications

• Soda M, Takada S, Takeuchi K, Choi YL, Enomoto M, Ueno T, Haruta H, Hamada T, Yamashita Y, Ishikawa Y, Sugiyama Y, Mano H. A mouse model for EML4-ALK-positive lung cancer. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19893-7. doi: 10.1073/pnas.0805381105. Epub 2008 Dec 8.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: August 8, 2012
• First Submitted That Met QC Criteria: August 9, 2012
• First Posted (ESTIMATE): August 10, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 9, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: RT-qPCR; IHC; Non-small cell lung cancer.; Diagnosis,; Adenocarcinoma,; ALK,; FISH,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: INCAN/CC/039/11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED