Lung Cancer

Primary Authors Wallander, Michelle L., PhD. Vaughn, Cecily P., MS. Samowitz, Wade S., MD.

Key Points

Molecular Markers in Lung Cancer

The presence of molecular markers in non-small cell lung cancer (NSCLC) is associated with responsiveness to targeted therapies. Simultaneous ordering of EGFR, ALK, ROS1 and consideration of KRAS, RET, BRAF, and other more rare mutations are recommended for advanced stage adenocarcinoma or mixed adenocarcinoma subtypes. Testing may be considered on small samples even in the absence of adenocarcinoma as sampling bias may occur and mixed adenocarcinoma tumors may be missed. At a minimum, testing should include EGFR mutation and ALK rearrangement detection (ASCO/CAP/IASLC/AMP, 2014). The NCCN guidelines strongly recommend using multiplex or next generation sequencing (NGS) which detect both common and rare mutations to optimize patient therapy (NCCN, 2015). Test results aid in the selection of targeted therapy, which involves inhibition of tyrosine kinase activity to diminish tumor growth.

  • EGFR

    EGFR (epidermal growth factor receptor) gene

    Pathophysiology

    Receptor tyrosine kinase in involved in cell proliferation and survival

    Mutations

    Certain EGFR gene mutations are associated with increased sensitivity to TKIs

    • Most commonly exon 19 deletions or exon 21 (L858R) substitution

    T790M mutation

    • Associated with decreased sensitivity to TKIs
    • Usually develops when treatment resistance occurs

    Lack of EGFR mutations (wild type) is associated with decreased sensitivity to TKIs

    Mutation status of EGFR does not appear to predict response to treatment with EGFR monoclonal antibody (cetuximab)

    Population characteristics associated with mutation

    10-15% of adenocarcinomas

    Associated with Asian ethnicity, female sex, and nonsmoking or light smoking status (<10 packs per year)

    Testing available

    ARUP tests

    • Lung Mutation and Translocation Panel by Next Generation Sequencing 2011612
    • Lung Cancer Panel 2008894 – includes EGFR, ALK, and ROS1
    • Lung Cancer Panel with KRAS 2008895 – includes KRAS, EGFR, ALK, and ROS1
    • EGFR Mutation Detection by Pyrosequencing 2002440

    Mutational analysis is preferred over gene amplification (ASCO/CAP/IASLC/AMP, 2014; NCCN, 2015)

    • Mutational testing should detect mutations in samples with at least 50% tumor cells (25% mutant alleles), although laboratories are strongly encourage to use more sensitive tests (eg, NGS) that are able to detect mutations in specimens with as little as 10% tumor cells

    NGS is recommended by NCCN and offers broader exon coverage

    IHC and FISH are not recommended

    Presence of EGFR mutation is usually mutually exclusive for ALK translocation

  • ALK

    ALK (anaplastic lymphoma receptor tyrosine kinase) gene

    Pathophysiology

    Fusion of ALK gene with echinoderm microtubule-associated protein-like-4 (EML-4) or other fusion partners mediates ligand-independent oligomerization of ALK protein, resulting in ALK kinase activation

    • Functions as potent oncogenic driver

    Translocations

    Certain ALK rearrangements are associated with increased sensitivity to specific TKIs (ALK/MET/ROS1 TKIs [eg, crizotinib])

    • Decreased sensitivity to EGFR TKIs

    Translocation partners

    • EML4, HIP1, KIF5B, KLC1, TPR

    Population characteristics associated with mutation

    4-7% of adenocarcinoma

    Associated with young age, male sex, nonsmoking or light smoking status (<10 packs per year), signet rings, and mucinous subtypes

    Testing available

    ARUP tests

    • Lung Mutation and Translocation Panel by Next Generation Sequencing 2011612
    • Lung Cancer Panel 2008894 – includes EGFR, ALK, and ROS1
    • Lung Cancer Panel with KRAS 2008895 – includes KRAS, EGFR, ALK, and ROS1
    • ALK (D5F3) with Interpretation by Immunohistochemistry 2007324
    • ALK (D5F3) by Immunohistochemistry with Reflex to ALK Gene Rearrangements by FISH 2011431
    • ALK Gene Rearrangements by FISH, Lung 2006102

    Detection of mutation is a prerequisite for crizotinib treatment in U.S.

    NGS is recommended by NCCN for the detection of gene fusion transcripts

    IHC detects protein expression and is a surrogate marker for ALK gene fusion; more cost-effective and efficient compared to FISH and RT-PCR

    RT-PCR does not detect all ALK fusion partners and is therefore not recommended (ASCO/CAP/IASLC/AMP, 2014)

    FISH interpretation may be challenging due to small inversions involving chromosome 2p (2p21 and 2p23) and does not identify translocation partner

    Presence of ALK gene rearrangements is generally mutually exclusive of EGFR and KRAS gene mutations

    KRAS

    KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog I) gene

    Pathophysiology

    RAS family of genes regulates signal conduction pathways that control cell growth

    Three distinct genes – HRAS, NRAS, and KRAS

    Mutation

    Almost all RAS mutations in NSCLC are in KRAS gene

    Generally associated with decreased sensitivity to EGFR TKIs and overall poor prognosis

    • Mutations in both EGFR and KRAS genes are associated with decreased sensitivity to TKIs despite the presence of EGFR mutation

    Population characteristics associated with mutation

    25-30% of adenocarcinomas

    Associated with mucinous subtype and current smoker status

    Testing available

    ARUP tests

    • Lung Mutation and Translocation Panel by Next Generation Sequencing 2011612
    • Lung Cancer Panel with KRAS 2008895 – includes KRAS, EGFR, ALK (D5F3), and ROS1
    • KRAS Mutation Detection 0040248

    Mutation testing is test of choice

    NGS is recommended by NCCN and offers broader exon coverage

    Testing for KRAS is not recommended as a sole determinant for EGFR-directed therapy

    Presence of KRAS gene mutations is generally mutually exclusive of EGFR mutations and ALK rearrangements

    ROS1

    ROS1 (c-ros oncogene 1, receptor tyrosine kinase) gene

    Pathophysiology

    Receptor tyrosine kinase is involved in cell proliferation

    ROS1 gene rearrangement and fusion with multiple known partners mediates constitutive ROS1 kinase activation

    Inhibition of tyrosine kinase activity diminishes tumor growth

    Translocations

    Generally associated with increased sensitivity to ALK/MET/ROS1 TKIs (eg, crizotinib) and decreased sensitivity to EGFR TKIs

    Translocation partners

    • CD74, EZR, GOPC, LRIG3, SDC4, SLC34A2, TPM3

    Population characteristics associated with mutation

    1-2% of adenocarcinomas

    Associated with Asian ethnicity, young age, nonsmoking or light smoker status (≤10 packs per year history)

    Testing available

    ARUP tests

    • Lung Mutation and Translocation Panel by Next Generation Sequencing 2011612
    • Lung Cancer Panel 2008894 – includes EGFR, ALK, and ROS1
    • Lung Cancer Panel with KRAS 2008895 – includes KRAS, EGFR, ALK, and ROS1
    • ROS1 with Interpretation by Immunohistochemistry with Reflex to FISH if Equivocal 2008414
    • ROS1 by FISH 2008418

    IHC detects protein expression and is a surrogate marker for ROS1 gene fusion

    • More cost effective and efficient when compared to FISH, but FISH is indicated for equivocal results by IHC
    • FISH detects gene rearrangements but is more costly than IHC

    NGS is recommended by NCCN for the detection of gene fusion transcripts

    Presence of ROS1 gene rearrangements is generally mutually exclusive of EGFR and KRAS gene mutations

    BRAF

    BRAF(B-Raf proto-oncogene) gene

    Pathophysiology

    Activates MAPK pathway, links with tyrosine kinases

    Mutation

    Generally associated with increased sensitivity to TKIs (eg, vemurafenib)

    Population characteristics associated with mutation

    1-4% of adenocarcinomas

    Associated with female sex and smoking

    Testing available

    ARUP tests

    • Lung Mutation and Translocation Panel by Next Generation Sequencing 2011612
    • BRAF Codon 600 Mutation Detection by Pyrosequencing 2002498

    BRAF codon 600 mutation testing by pyrosequencing detects most common mutation

    NGS offers broader exon coverage

    RET

    RET(ret proto-oncogene) gene

    Pathophysiology

    RET gene rearrangement and fusion with multiple known partners mediates constitutive RET kinase activation

    Generally associated with sensitivity to ALK/MET/ROS1 TKIs (eg, vandetanib, cabozantinib)

    • Decreased sensitivity to EGFR TKIs

    Translocations

    Translocation partners

    • CCDC6, CUX1, KIF5B
    Population characteristics associated with mutation1-2% of adenocarcinomas

    Testing available

    ARUP test

    • Lung Mutation and Translocation Panel by Next Generation Sequencing 2011612

    NGS is recommended by NCCN for the detection of gene fusion transcripts

    IHC has not been established for RET detection

    FISH detects gene rearrangement but is time intensive and costly

Diagnosis

Indications for Testing

  • New pulmonary mass

Laboratory Testing

  • Serum testing is not helpful in diagnosing lung cancer; however, baseline testing (eg, CBC with differential, liver function) may be performed as a general screen for metastasis
  • Other testing
    • Neuron-specific enolase (NSE), serum – may have diagnostic value for small cell lung cancer (SCLC)

Imaging Studies

  • Chest x-ray, CT scan, MRI provide basis for initial testing

Histology

  • Invasive testing to obtain tissue is necessary for diagnosis
    • Bronchoscopic biopsy
    • Mediastinal node sampling
    • Fine needle aspiration using CT guidance
    • Open lung biopsy
    • Fine needle aspiration using endobronchial ultrasound (EBUS)
  • Immunohistochemistry
    • Should be used adjunctly and interpreted in clinical context
    • Squamous cell carcinoma (SCC)
      • Usually negative for CK 7, CK 20, TTF-1
      • Does not typically require immunohistochemical staining for diagnosis
    • Primary adenocarcinoma and bronchioalveolar carcinoma
      • Positive for CK 7, napsin A, and thyroid transcription factor-1 (TTF-1); negative for CK 20
      • Primary mucinous adenocarcinoma – positive for CK 7 and CK 20, negative for TTF-1
    • SCLC and neuroendocrine carcinomas
      • Typically negative for CK 7, CK 20
      • Typically positive for keratin epithelial membrane antigen and TTF-1
      • Positive for neuroendocrine markers such as chromogranin A, CD56 (NCAM), synaptophysin, NSE
    • Dysregulation in tumor progression, therapeutic target – c-MET
    • Markers used to differentiate cancers

      Markers

      Use

      Comments

      p63 and CK 5,6 – positive

      TTF-1 – negative

      Differentiating poorly differentiated SCC from SCLC

      Supports SCC

      CEA-P, b72.3, Ber-EP4, MOC-31, and TTF-1

      Differentiating NSCLC adenocarcinoma from mesothelioma

      Positive in NSCLC

      Negative in mesothelioma

      Micro RNA (mRNA) expression

      Differentiating NSCLC from SCLC

      CK 7+/CK 20-, TTF-1+ – pulmonary

      CK 7-/CK20+, TTF-1- – colorectal

      Differentiating metastatic adenocarcinomas

       

      CDX2

      Differentiating primary lung tumors from metastatic gastrointestinal tumors

      Specific for gastrointestinal tumors

  • Molecular markers
    • Most useful for therapy planning in advanced stages of adenocarcinoma and mixed adenocarcinoma subtypes (ASCO/CAP/IASLC/AMP 2014) – see Key Points

Solitary Pulmonary Nodule

  • Usually found incidentally on chest x-ray (0.09-0.2% of all x-rays)
    • 35% are malignant
  • Histologic diagnosis required in the following situations
    • Patient is ≥35 years
    • Nodule is >10 mm diameter
    • Growth of lesion
    • Lack of calcification
    • Adenopathy
    • Positive PET scan
    • No previous imaging to review in order to determine if nodule has changed in size

Prognosis

  • Markers
    • EGFR, KRAS, ALK, ROS1, RET, BRAF, MET, ERBB2 (HER2), and other mutations – refer to Key Points section
      • Establish eligibility for therapies such as tyrosine kinase and ALK inhibitors
  • Promising markers
    • Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1)
      • T-cell coinhibitory receptor and ligand function as immune checkpoint
        • PD-L1 is ligand for PD-1 
        • PD-L1 expression facilitates immune system evasion by inhibiting T-cell activation
        • PD-1 and PD-L1 are expressed by a variety of solid tumors, including NSCLC
        • Detection of PD-1 and PD-L1 expression by immunohistochemistry may predict response to immunotherapy with monoclonal antibodies
    • Cytokeratin-19 fragment (CYFRA 21-1)
      • Most sensitive tumor marker for NSCLC (particularly squamous)
      • Uses
        • Prognostication
          • Elevated pretreatment level – associated with unfavorable prognosis
        • Monitoring
          • Decreasing levels predict objective response to treatment
    • Neuron-specific enolase (NSE)
      • High specificity for SCLC
      • May be useful in assessing prognosis in NSCLC and SCLC
      • Currently in clinical use, but prognostic value has not been validated in high-level study
    • p53 – tumor suppressor protein
      • Presence in patients with NSCLC is prognostic of short survival time and potential benefit from adjuvant chemotherapy
    • Pro GRP – SCLC
    • CA-125 (available as an immunohistochemical stain) – NSCLC
    • STK11 – adenocarcinoma
    • Tumor M2-PK (TU M2-PK) – all types
    • BCL-2 (available as an immunohistochemical stain) – SCLC
    • ERCC1 expression – high level
    • RRM1 expression – high level

Differential Diagnosis

Screening

  • Screening recommendations for lung cancer

    Screening Recommendations for Lung Cancer

     

    Recommendation

    Age

    Smoking history

    Methodology

    Additional information

    American College of Chest Physicians (ACCP) (2013)

    Annual screening for high-risk individuals based on results of the NLST*

    55-74 years

    ≥30 pack per year smoking history and currently smoke or smoking cessation within the past 15 years

    LDCT**

    Screening offered only in clinical settings similar to those in the trial

    American Society of Clinical Oncology (ASCO) (2012)

    Annual screening for high-risk individuals based on results of the NLST*

    55-74 years

    ≥30 pack per year smoking history and currently smoke or smoking cessation within the past 15 years

    LDCT**

    Screening offered only in clinical settings similar to those in the trial

    American Thoracic Society (ATS)(2014)

    Annual screening for high-risk individuals based on results of the NLST*

    55-80 years

    ≥30 pack per year smoking history and currently smoke or smoking cessation within the past 15 years

    LDCT**

    Screening offered only in clinical settings similar to those in the trial

    National Comprehensive Cancer Network (NCCN) (2015)

    Annual screening for high-risk individuals for 2 years

    55-74 years

    ≥30 pack per year smoking history and if former smoker, smoking cessation ≤15 years

    LDCT**

    Screening not recommended for

    • Moderate-risk individuals – ≥50 years with ≥20 pack per year smoking history or secondhand smoke exposure but no additional risk factors
    • Low-risk individuals – <50 years or <20 pack per year smoking history

    ≥50 years

    ≥20 pack per year smoking history and one additional risk factor (other than secondhand smoke)

    Additional risk factors – radon exposure; occupational exposure; cancer history; family history; COPD or pulmonary fibrosis

    U.S. Preventive Services Task Force (USPSTF) (2013)

    Annual screening for high-risk individuals

    55-80 years

    ≥30 pack per year smoking history and currently smoke or smoking cessation within the last 15 years

    LDCT**

    Screening can be discontinued once an individual has not smoked for 15 years or develops a health problem that limits life expectancy or the ability to have curative surgery

    American Association for Thoracic Surgery (AATS)(2012)

    Annual screening in current and former smokers

    55-79 years

    30 pack per year smoking history

    LDCT**

     

    50-79 years

    20 pack per year smoking history with additional comorbid conditions that produce a cumulative risk for cancer of at least 5% over the next 5 years

    55-79 years

    Long-term cancer survivors

    American Cancer Society (ACS)(2013)

    Annual screening in high-risk individuals with relatively good health who meet NLST* criteria

    55-74 years

    ≥30 pack per year smoking history and currently smoke or smoking cessation within the last 15 years

    LDCT**

    • Recommends against the use of chest radiography
    • Strongly suggests individuals enter an organized screening program that has experience in LDCT**

    *NLST (National Lung Screening Trial ) – high-risk smokers and former smokers 55-74 years with ≥30 packs per year smoking history and no history of lung cancer (former smokers must have quit within the past 15 years)

    **LDCT – low-dose computed tomography

Monitoring

  • Recommended monitoring (postcurative approach)
    • History and physical, chest x-ray, CBC and chemistries every 3-6 months for first 2 years (National Comprehensive Cancer Network [NCCN] recommends CT every 6 months in non-small cell lung cancer [NSCLC])
  • Small-cell lung cancer (SCLC)
    • Serial neuron-specific enolase (NSE) testing may be useful for monitoring tumor recurrence in SCLC
  • NSCLC
    • CK 19 – potential role for monitoring therapy in advanced NSCLC

Clinical Background

Lung cancer is the leading cause of cancer-related mortality in the U.S. and worldwide.

Epidemiology

  • Incidence – 62.5/100,000
    • Leading cause of cancer in the U.S. (NCCN, 2015)
  • Age – peak incidence is 65-74 years; median is 71 years
  • Sex – M>F, minimal
    • Female prevalence has increased; male prevalence has stabilized
  • Ethnicity – highest incidence in African American males

Risk Factors

  • Tobacco use – 85-90% of all lung cancers attributed to tobacco use
    • 13-fold increase in risk for primary user
    • Secondhand smoke exposure – 20-30% increased risk for those who live/ have lived with smokers
  • Radon exposure – likely main cause of lung cancer in nonsmokers
  • Asbestos exposure – cumulative risk; estimated to cause 3-4% of cases
    • Risk increased if patient also smokes
  • Occupational exposure to carcinogens (eg, bis(chloromethyl)ether, polycyclic aromatic hydrocarbons, chromium, nickel, organic arsenic)
  • Previous chest irradiation
  • Genetic – positive family history combined with tobacco use increases the risk

Pathophysiology

  • Any tumor arising from respiratory epithelium or pneumocytes
  • Two main types
    • Non-small cell lung cancer (NSCLC) – ~85% of all lung cancers
      • Adenocarcinoma (non-squamous cell) – most common
        • Occurs in glandular tissue of lung lining
      • Squamous (epidermoid) cell carcinoma (SCC)
      • Large cell (large cell anaplastic), other types
    • Small cell lung cancer (SCLC) – ~15% of all lung cancers
      • Epithelial tumor of small cells
        • 95% arise in lung; may also arise from extrapulmonary sites (eg, nasopharynx, gastrointestinal tract, genitourinary tract)
      • Nearly all cases result from smoking
      • Two subtypes
        • Small cell carcinoma (oat cell)
        • Combined small cell carcinoma
  • Other tumors (rare)
  • Undifferentiated bronchial-gland tumors, sarcomas, neuroendocrine tumors

Clinical Presentation

  • 20% of cases incidentally identified by chest x-ray for other reasons (patients are typically asymptomatic)
  • Symptoms based on area of tumor growth
    • Central lesion – cough, wheeze, hemoptysis, stridor, dyspnea, postobstructive pneumonia
    • Peripheral lesion – pleural/chest wall pain, cough, dyspnea
    • Invasion and obstruction of adjacent structures
      • Tracheal obstruction – dyspnea, wheezing
      • Esophageal compression – dysphagia
      • Recurrent laryngeal nerve invasion – hoarseness
      • Phrenic nerve invasion – diaphragmatic paralysis
      • Sympathetic nerve invasion – Horner syndrome
        • Ptosis
        • Miosis
        • Enophthalmos
        • Unilateral loss of sweating
      • Invasion of lung apex – Pancoast tumor, superior vena caval syndrome
    • Distant metastasis
      • Superior vena caval syndrome
      • Pericardial tamponade
      • Pleural effusions
      • Pathologic bone fractures
      • Adrenal insufficiency (rare) 
    • Paraneoplastic syndromes – common; may be first presenting symptoms of lung cancer (SCLC in particular)

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Lung Mutation and Translocation Panel by Next Generation Sequencing 2011612
Method: Massive Parallel Sequencing

Most comprehensive screening panel for determining eligibility for TKI therapy; most useful for tumors with adenocarcinoma or mixed adenocarcinoma histology

Simultaneously detects hotspot mutations and fusion transcripts in genes associated with lung adenocarcinoma

DNA is amplified for detection of the following – AKT1, ALK, BRAF, EGFR, ERBB2, ERBB4, KRAS, NRAS, PIK3CA

RNA is reverse transcribed and then amplified to detect ALK, RET, and ROS1 gene fusion transcripts

Mutation status is determined using massively parallel sequencing (NGS)

Analytical sensitivity – 5% mutant alleles

Results of this test should be interpreted within the context of clinical findings

Not intended to detect minimal residual disease

 
Lung Cancer Panel 2008894
Method: Polymerase Chain Reaction/Pyrosequencing/Immunohistochemistry

Screening panel to determine eligibility for TKI therapy

Detects EGFR mutations and ALK, and ROS1 translocations

Results must be interpreted in the context of morphological and other relevant data

Tests should not be used alone to diagnose malignancy

Results may be compromised if the recommended tissue fixation procedures are not followed

Not intended to detect minimal residual disease

 
Lung Cancer Panel with KRAS 2008895
Method: Polymerase Chain Reaction/Pyrosequencing/Immunohistochemistry

Screening panel to determine eligibility for TKI therapy

Detects KRAS and EGFR mutations and ALK and ROS1 translocations

Results must be interpreted in the context of clinical findings and morphological and other relevant data

Tests should not be used alone to diagnose malignancy

Results may be compromised if the recommended tissue fixation procedures are not followed

Not intended to detect minimal residual disease

 
KRAS Mutation Detection 0040248
Method: Polymerase Chain Reaction/Pyrosequencing

Single gene assay

Detects activating KRAS mutations (codons 12, 13, and 61) associated with anti-EGFR therapy resistance

   
EGFR Mutation Detection by Pyrosequencing 2002440
Method: Polymerase Chain Reaction/Pyrosequencing

Single-gene test predicts response to TKI therapy

Detects mutations at codons 719 (exon 18), 768 and 790 (exon 20), 858 and 861 (exon 21); detects deletions in exon 19

   
ALK (D5F3) with Interpretation by Immunohistochemistry 2007324
Method: Immunohistochemistry

Order if no mutations detected in either KRAS or EGFR gene

Cost-effective, efficient screen for all ALK fusion proteins

D5F3 clone more sensitive than ALK1 clone for detection of ALK protein expression in lung cancer

   
ROS1 with Interpretation by Immunohistochemistry with Reflex to FISH if Equivocal 2008414
Method: Immunohistochemistry

Cost-effective, efficient screen for ROS1 fusion proteins

Reflex pattern – if ROS1 by IHC is equivocal, then ROS1 by FISH will be added

   
ROS1 by FISH 2008418
Method: Fluorescence in situ Hybridization

Detects all ROS1 fusions

   
EGFR Gene Amplification by FISH 2008605
Method: Fluorescence in situ Hybridization

Not recommended for lung cancer mutation screening

Aids in prognostication and therapeutic decisions for neoplasms where amplification has been demonstrated

Tissue fixed in alcohol based or non-formalin fixatives have not been tested using this method

 
ALK Gene Rearrangements by FISH, Lung 2006102
Method: Fluorescence in situ Hybridization

Screening test for all ALK fusions; does not identify the translocation partner or variant

Use this test especially if companion diagnostic test for crizotinib is required

   
PD-L1 by Immunohistochemistry with Interpretation 2012105
Method: Immunohistochemistry
Screening test for monoclonal antibody therapy    
Lung Cancer Assessment and Early Detection (EarlyCDT) 2007513
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

May be useful as screening for patients deemed high risk for lung cancer

Consider in individuals 40-75 years of age with high risk for lung cancer

  • Primary – long-term smokers and ex smokers (>20 pack years)
  • Secondary – family history of lung cancer; environmental exposure (eg, asbestos, radon, radioactive materials); respiratory disease (eg, silicosis, berylliosis)

Diagnostic adjunct for individuals with indeterminate nodules on chest imaging

Individuals being serially followed for a lung nodule

Emerging test to aid in early detection of lung cancer; should be used with caution

No long-term trial data available to address mortality benefit

Use of this test will likely increase imaging for follow-up of abnormal tests

Small proportion of tested individuals have nonspecific immunoreactivity (prevents interpretation of test results)

Should not be used for individuals with history of any type of cancer

Should only be used in individuals deemed high risk; not validated in other populations

 
CYFRA 21-1 (Cytokeratin 19 Fragment), Serum 0081344
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Use for prognostication and monitoring in NSCLC

Clinical sensitivity – varies by disease stage

Analytical sensitivity – limit of detection is 0.5 ng/mL

Do not use for screening

Results obtained with different methods or kits cannot be used interchangeably

Test interference – hemolyzed specimens; icteric specimens; lipemic specimens; interfering antibodies in specimen (human anti-mouse or heterophile antibodies)

CYFRA 21-1 may be elevated in benign respiratory disease and other cancers  (eg, urologic, gastrointestinal, gynecological)

 
Neuron Specific Enolase 0098198
Method: Quantitative Enzyme-Linked Immunosorbent Assay
Use for prognostication and monitoring in NSCLC

Do not use for screening

Results obtained with different methods or kits cannot be used interchangeably

 
Cytokeratin 7 (CK 7) by Immunohistochemistry 2003854
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Cytokeratin 20 (CK 20) by Immunohistochemistry 2003848
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Thyroid Transcription Factor (TTF-1) by Immunohistochemistry 2004166
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Chromogranin A by Immunohistochemistry 2003830
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
CD56 (NCAM) by Immunohistochemistry 2003589
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
p63 by Immunohistochemistry 2004073
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Cytokeratin 5,6  (CK 5,6) by Immunohistochemistry 2003851
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Carcinoembryonic Antigen, Polyclonal (CEA P) by Immunohistochemistry 2003827
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Breast Carcinoma b72.3 by Immunohistochemistry 2003445
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Anti-Human Epithelial Antigen, Ber-EP4 by Immunohistochemistry 2003463
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Epithelial-Related Antigen, MOC-31 by Immunohistochemistry 2003875
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Neuron Specific Enolase, Polyclonal (NSE P) by Immunohistochemistry 2004052
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
CDX2 by Immunohistochemistry 2003821
Method: Immunohistochemistry

Aid in differentiating primary lung tumors from metastatic GI tumors

Stained and returned to client pathologist for interpretation; consultation available if needed

   
c-MET by Immunohistochemistry 2008652
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Napsin A by Immunohistochemistry 2008716
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
P40 by Immunohistochemistry 2010142
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
PD-1 by Immunohistochemistry 2004085
Method: Immunohistochemistry

Aid in prediction of response to immune therapy

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Solid Tumor Mutation Panel by Next Generation Sequencing 2007991
Method: Massively Parallel Sequencing

Useful for prognosis and/or treatment of individuals with solid tumor cancer at initial diagnosis or in the presence of refractory disease

Analytic sensitivity – 5% mutant alleles

Simultaneously evaluates mutations in multiple genes, including EGFR, KRAS, NRAS, and BRAF

For a full list of the targeted regions of the above genes, click here

BRAF Codon 600 Mutation Detection by Pyrosequencing 2002498
Method: Polymerase Chain Reaction/Pyrosequencing

Single gene assay

Detects activating BRAF mutations (codon 600) associated with anti-EGFR therapy resistance

Use prior to BRAF V600E inhibitor initiatio

Carcinoembryonic Antigen 0080080
Method: Quantitative Electrochemiluminescent Immunoassay

Prognostication and monitoring in lung cancer

Squamous Cell Carcinoma Antigen, Serum 0081054
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Prognostication and monitoring in lung cancer