Prognostic Immunohistochemistry and Predictive Immunohistochemistry with Lung Cancer

CONTENT:

6.6.3 Prognostic Immunohistochemistry (IHC) of the Lung
6.6.4 ‘Predictive’ Lung Immunohistochemistry (IHC): EGFR and ALK
i. Epidermal Growth-Factor Receptor (EGFR) Expression
ii. Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement

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6.6.3 Prognostic Immunohistochemistry (IHC) in Lung Cancer

A ‘prognostic‘ factor in the analysis of lung tumor tissue, provides information on the clinical outcome (prognosis) at the time of diagnosis; it is independent of tumor therapy.

A ‘predictive‘ factor in the analysis of lung tumor tissue, provides an indication of the likelihood of a tumor response to a given treatment (or ‘targeted therapy’).

Prognostic and predictive lung tumor characteristics may be classified separately there are some factors that are both prognostic and predictive (e.g., the presence of EGFR mutations).

A clinically useful prognostic tumor marker should demonstrate these three properties:

analytical validity;
clinical validity, and
clinical utility.

Additionally, it is advantageous that a prognostic tumor marker to have these additional properties:

provide independent and significant value,
be reproducible,
are widely available,
be interpretable, and
must not use up the remaining tissue needed for other tests.

Prognostic markers in lung cancer diagnosis should be able to add to the TNM staging system (particularly in stage I).

Lung cancer molecular markers have been studied to refine risk stratification beyond staging. These markers effect malignant transformation and the metastatic process through five primary oncogenic mechanisms:

cell growth stimulation (EGFR, Erb-B2),
cell cycle regulation (p16INK4A, retinoblastoma [Rb], Ki-67),
interference with apoptosis (p53, Bcl-2),
tumor angiogenesis (factor VIII–related antigen, CD31, vascular endothelial growth-factor C), and
invasive cellular adhesion (CD44).

The majority of these factors do not show independent prognostic value. However, IHC is available for these prognostic markers.

I’m a bit confused between prognostic and predictive.

To summarize, prognostic relates to the prognosis or likely outcome of the disease and a predictive value relates to likely response to treatment.

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6.6.4 Predictive Immunohistochemistry (IHC): EGFR and ALK

A ‘predictive‘ factor in lung cancer is capable of providing information on the likelihood of tumor response to a given therapy.

With the discovery of new cancer biomarkers that may direct patient treatment, the detection of ‘predictive’ biomarkers in lung tumor tissue, using IHC has become the basis of ‘targeted therapy’ or ‘personalized medicine’.

i. Epidermal Growth-Factor Receptor (EGFR) Expression

Recent clinical trials have shown that Non-Small Cell Lung Cancer (NSLC) sub-typing in diagnosis has the following key roles:

Patient response rates and survival with the chemotherapeutic agent pemetrexed is significantly better in patients with non-squamous histology.
Pulmonary hemorrhage with bevacizumab treatment of advanced lung cancer is associated with squamous cell histology.
NSCLC with EGFR mutations are more responsive to EGFR tyrosine kinase inhibitors (TKI) than wild-type tumors. As almost all EGFR mutant NSCLC are adenocarcinomas, histological subtyping is important in determining which cases should undergo mutation testing.

Any routinely available pathological lung tissue specimen can be used for EGFR mutation analysis.

Figure 6.14 EGFR and ALK Expression in Adenocarcinoma
of the Lung Demonstrated by IHC.

A. Photomicrograph of IHC for EGFR on a section of lung tumor.
Immunostaining (brown) is seen on the cell membrane in the majority
of cancer cells. (IHC for EGFR x 60). B. Photomicrograph of IHC for
ALK on a section of lung tumor. Immunostaining (brown) is seen in
the cell cytoplasm and around the cell nuclei in the majority of cancer
cells. (IHC for ALK x 40)

ii. Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement

An uncommon molecular subtype of NSCLC is characterized by rearrangements of the ALK gene. These lung tumors respond to targeted ALK inhibitors . The incidence of ALK rearrangements in NSCLC is approximately 4 %. EML4-ALK (echinoderm microtubule-associated protein-like 4 -anaplastic lymphoma kinase) translocations are sensitive to ALK kinase inhibitors. EML4-ALK is found almost exclusively in lung adenocarcinomas.

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References:

Buccheri G, Ferrigno D. (1994) Prognostic factors in lung cancer: Tables and Comments. Eur Respir J, 1994, 7, 1350–1364. (Retrieved 29^th April 2015): http://erj.ersjournals.com/content/7/7/1350.full.pdf

Selinger CI, Rogers T-M, Russell PA et al. (2013). Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization. Mod. Pathol 26, 1545–1553. (Retrieved 19^th Feb 2015): https://www.ncbi.nlm.nih.gov/pubmed/23743928

More references for this section are on this page .

Patient Information:

Global Resource for Advancing Cancer Education (GRACE) An Overview of Molecular Markers in Lung Cancer (Retrieved 28^th April 2015): http://cancergrace.org/lung/2010/10/10/overview-of-molecular-markers-in-lung-cancer/

Memorial Sloan Kettering Cancer Center Pattern in Lung Cancer Pathology May Predict Cancer Recurrence after Surgery (Retrieved 28^th April 2015): http://www.mskcc.org/blog/pattern-lung-pathology-may-predict-recurrence-after-surgery

More patient information for this section is on this page .

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