Lung Cancer

What is Lung Cancer?

Lung cancer is one of the most common types of cancer. While a significant portion is directly associated with smoking, there are also types that are not linked to smoking. Primary lung cancers, meaning cancers that originate in the lungs, are classified into two main categories:

• Small Cell Lung Cancer (SCLC): A rapidly growing and fast-progressing form.

• Non-Small Cell Lung Cancer (NSCLC): Approximately 80-85% of cases fall into this group. It has three known subtypes: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma.

Among non-small cell lung cancers, lung adenocarcinoma is the most common type. It originates in the glands located in the air sacs (alveoli) and the inner lining of the bronchi in the lungs. Adenocarcinoma can occur in many glandular tissues and is known for secreting mucus. These cells tend to grow more slowly.

This type of cancer typically begins in the peripheral lung tissue (the outer part of the lung) and tends to produce symptoms at earlier stages. Therefore, adenocarcinoma is often diagnosed at earlier stages. Certain individuals are at higher risk—smoking and tobacco use increase the risk, but adenocarcinoma can also develop in people who have never smoked. In fact, adenocarcinoma is the most common type of lung cancer in non-smokers. Overall, while lung cancer is the most common cancer type in men, adenocarcinoma is the most frequently observed lung cancer in women. The rate of adenocarcinoma is even higher in women compared to men. The majority of lung cancers diagnosed in non-smokers occur in women.

Genetic Tests for Lung Cancer Risk Assessment

Genetic tests used for individuals with a personal or family history of lung cancer aim to assess cancer risk, understand potential preventive measures, and determine appropriate screening methods for early detection. Additionally, by examining genes related to drug metabolism, these tests can help guide the selection of medications and appropriate dosages for treatment.

Familial Lung Cancer Screening Test

For hereditary (familial) cancer screening, panel tests are utilized. Different panels may be used by clinicians. The panel used in our center includes approximately 220 genes known to be associated with cancer, as well as around 400 candidate genes suspected to be linked to cancer. As new cancer-related genes are identified, they are added to the panel, which is regularly updated.

Genetic Tests Used for Lung Cancer Diagnosis

These genetic tests identify specific genetic changes in the patient’s tumor cells, helping to understand treatment options and prognosis. The most common genetic tests for lung cancer include:

• EGFR (Epidermal Growth Factor Receptor) Mutation Test: Mutations in the EGFR gene play a crucial role in determining treatment options for lung cancer patients. Patients with EGFR mutations may respond better to targeted therapies (e.g., EGFR inhibitors).

• ALK (Anaplastic Lymphoma Kinase) Rearrangement Test: ALK gene rearrangement is a genetic change found in certain types of lung cancer. Patients with ALK rearrangements may respond to targeted therapies such as ALK inhibitors.

• ROS1 Rearrangement Test: Rearrangement of the ROS1 gene is a rare subtype of lung cancer. ROS1-positive patients may benefit from treatments targeting ROS1.

• BRAF V600E Mutation Test: The V600E mutation in the BRAF gene is a variant that can be present in lung cancer and may respond to targeted therapies.

• PD-L1 Immunohistochemistry Test: The presence or absence of the PD-L1 protein can serve as a predictor for immunotherapy treatments. This test helps assess the likelihood of response to immunotherapy.

• Tumor Mutation Panel: A genetic panel test performed using next-generation sequencing (NGS) technology to detect multiple genetic changes simultaneously. These tests can be performed on tumor tissue or through a liquid biopsy by analyzing serum obtained from a blood sample. The test evaluates the presence of mutations in many genes, as well as microsatellite instability and tumor mutation burden. These panels provide a detailed analysis of the tumor’s genetic profile. They help identify the unique characteristics of the tumor in the patient, which is important for determining personalized treatment options and prognosis. Different centers may offer tests covering varying numbers of genes.

In our center, we use a panel that includes a broad range of genetic mutations and also evaluates Tumor Mutation Burden (TMB), PDL/PDL1, and Microsatellite Instability. This panel also simultaneously analyzes polymorphisms related to the toxic effects and efficacy of classical chemotherapeutic agents in patients. For patients diagnosed with lung cancer, it is recommended to consult an oncologist and a genetics specialist to evaluate treatment options.

• RNA Fusion (Gene Fusion) Panel: This method involves extracting RNA from tumor tissue and using the NGS technique to visualize all RNAs. It is used to assess fusions and some deletions and duplications. RNA sequencing (RNA-seq) plays a crucial role in identifying potential drugs and prognostic markers for patients.

Genetic Tests Commonly Used for Lung Cancer

• EGFR (Exons 18-21, including p.T790M mutation) (Next-Generation Sequencing - NGS)

• KRAS (Codons 12, 13, 61, 117, 146) (Next-Generation Sequencing - NGS)

• ALK Rearrangements (FISH)

• ROS1 Rearrangements (FISH)

• HER2 / CerbB2 (FISH)

• ATRX (Sequencing analysis) (in non-small cell lung cancer)

• MSI (Microsatellite Instability)

• MET (FISH) (Amplification)

• RET Rearrangements (FISH - Breakapart)

• PDL1 Expression

What Are the Symptoms of Lung Cancer?

The symptoms of lung cancer may vary depending on the type and stage of the disease, as well as from person to person. Some common symptoms include:

• Cough: A persistent or bloody cough is a potential symptom of lung cancer.

• Shortness of Breath: Difficulty breathing or a sensation of rapid breathing.

• Chest Pain: Pain or discomfort in the chest area.

• Wheezing: A whistling sound while breathing.

• Hemoptysis (Coughing up Blood): Presence of blood during coughing or in sputum.

• Loss of Appetite and Weight Loss: Decreased appetite and weight loss.

• Hoarseness: Chronic hoarseness or voice changes.

• Fatigue and Weakness: Sudden onset of fatigue.

• Frequent Infections: Recurring or chronic respiratory infections such as bronchitis or pneumonia.

• Clubbing (Fingertip Enlargement): Swelling or enlargement of the fingertips.

It is important to note that these symptoms may also indicate various other health conditions. Therefore, individuals experiencing these symptoms should consult a healthcare professional. Lung cancer often does not present symptoms in its early stages and becomes more noticeable as it progresses. Therefore, individuals with risk factors are encouraged to undergo regular health screenings and medical check-ups.

Early Detection of Lung Cancer

As with all cancers, early detection and treatment significantly improve outcomes in lung adenocarcinomas. Therefore, individuals with risk factors (such as smoking or family history) should undergo regular health check-ups and pay attention to potential symptoms.