Molecular Pathology

Molecular Pathology Indian Medical PG Question 1: Techniques used for protein expression proteomics study include:

• A. PolyAcrylamide Gel Electrophoresis (PAGE)
• B. Gene Expression Analysis (indirectly related to proteomics)
• C. Mass Spectrometry
• D. All of the options (Correct Answer)

Molecular Pathology Explanation: ***All of the options*** - All listed techniques—**Polyacrylamide Gel Electrophoresis (PAGE)**, **Gene Expression Analysis**, and **Mass Spectrometry**—are used in protein expression proteomics studies, either directly or indirectly, to analyze and quantify proteins. - The integration of these various techniques provides a comprehensive approach to understanding protein expression profiles. *PolyAcrylamide Gel Electrophoresis (PAGE)* - **PAGE** (including 1D and 2D-PAGE) is a fundamental technique for separating proteins based on their **molecular weight** and **isoelectric point**, which is crucial for visualizing and quantifying expressed proteins. - It often serves as an initial separation step before more detailed analysis, such as **mass spectrometry**. *Gene Expression Analysis (indirectly related to proteomics)* - Although **gene expression analysis** (e.g., using **RT-PCR** or **microarrays**) measures mRNA levels, it is indirectly related to proteomics because mRNA levels often **correlate with protein levels**. - It provides insights into the **transcriptional regulation** that influences protein expression, complementing direct protein analysis. *Mass Spectrometry* - **Mass spectrometry** is a powerful and widely used technique in proteomics for **identifying, quantifying, and characterizing proteins** and peptides by measuring their **mass-to-charge ratio**. - It can be used for both **discovery proteomics** (identifying novel proteins) and **targeted proteomics** (quantifying specific proteins).

Molecular Pathology Indian Medical PG Question 2: Which of the following is a primarily RNA based technique?

• A. Western blotting
• B. Northern blotting (Correct Answer)
• C. Southern blotting
• D. Sanger's technique

Molecular Pathology Explanation: ***Northern blotting*** - **Northern blotting** is a molecular biology technique used to study **gene expression** by detecting specific **RNA molecules** (mRNA) in a sample. - It involves separating RNA fragments by **gel electrophoresis**, transferring them to a membrane, and then detecting specific sequences using **labeled probes**. *Western blotting* - **Western blotting** is a technique used to detect specific **proteins** in a sample. - It involves separating proteins by **gel electrophoresis**, transferring them to a membrane, and then detecting specific proteins using labeled **antibodies**. *Southern blotting* - **Southern blotting** is a molecular biology method used for the detection of **specific DNA sequences** in DNA samples. - It involves separating **DNA fragments** by **gel electrophoresis**, transferring them to a membrane, and then hybridizing with a labeled probe. *Sanger's technique* - **Sanger sequencing**, or the **dideoxy chain-termination method**, is a widely used method for **DNA sequencing**. - It uses **dideoxynucleotides** to terminate DNA synthesis at specific bases, allowing the determination of the **DNA sequence**.

Molecular Pathology Indian Medical PG Question 3: Which of the following are correct with regard to lung cancer? 1. Surgical resection has a limited role in curative treatment of lung cancer. 2. Pattern of disease and prognosis of oat cell carcinoma are different to other varieties in the lungs. 3. Small cell lung cancer is a type of Neuroendocrine Tumour (NET). 4. Squamous cancer appears as a cavitating tumour in the lungs.

• A. 1, 3 and 4
• B. 2, 3 and 4 (Correct Answer)
• C. 1, 2 and 3
• D. 1, 2 and 4

Molecular Pathology Explanation: ***2, 3 and 4*** - **Oat cell carcinoma** (small cell lung cancer) is known for its **aggressive behavior**, rapid growth, early metastasis, and distinct response to chemotherapy and radiation rather than surgery, making its pattern and prognosis different from **non-small cell lung cancer (NSCLC)** types [1]. - **Small cell lung cancer (SCLC)** originates from **neuroendocrine cells** in the lung, classifying it as a type of **Neuroendocrine Tumour (NET)**, which explains its unique biological and clinical characteristics [1]. - **Squamous cell carcinoma** is often centrally located and can undergo central necrosis, leading to **cavitation** which appears as a cavitating tumor on imaging [1]. *1, 3 and 4* - This option is incorrect because statement 1, which suggests surgical resection has a limited role in curative treatment, is generally **false for non-small cell lung cancer (NSCLC)**, where surgery is the primary curative modality in early stages [1]. - While statements 3 and 4 are correct, the inclusion of incorrect statement 1 makes this option invalid. *1, 2 and 3* - This option is incorrect as statement 1 claiming a limited role for surgical resection in curative treatment is generally **false for NSCLC**, where localized tumors are ideally treated with surgery [1]. - Statements 2 and 3 are correct, but the inaccuracy of statement 1 renders this option incorrect. *1, 2 and 4* - This option is incorrect because statement 1, which states that surgical resection has a limited role in curative treatment, is generally **incorrect for early-stage NSCLC** [1]. - Although statements 2 and 4 are accurate, the error in statement 1 makes this combination incorrect.

Molecular Pathology Indian Medical PG Question 4: Which of the following is the most fundamental criterion that must be met by a disease before it is to be considered suitable for a screening programme? 1. The natural history of the disease should be adequately understood. 2. No effective treatment should exist for the disease. 3. The disease should not have a recognizable latent or asymptomatic stage. 4. There should be a test that can detect the disease prior to onset of signs and symptoms.

• A. 4. There should be a test that can detect the disease prior to onset of signs and symptoms.
• B. 3. The disease should not have a recognizable latent or asymptomatic stage.
• C. 1. The natural history of the disease should be adequately understood. (Correct Answer)
• D. 2. No effective treatment should exist for the disease.

Molecular Pathology Explanation: ***The natural history of the disease should be adequately understood.*** * This is the **most fundamental criterion** because understanding the natural history (progression from asymptomatic to symptomatic disease) allows for the identification of a **critical window** for early intervention through screening. * Without this knowledge, it's impossible to determine when to screen, what to screen for, or whether early detection will lead to a better outcome. *There should be a test that can detect the disease prior to onset of signs and symptoms.* * While important, the existence of a detectable test *before* symptoms is only useful if the **natural history** is understood, allowing for appropriate timing and interpretation of the test. * A test without understanding the disease's progression might lead to **overdiagnosis** or diagnosis at a stage where intervention is no longer effective. *The disease should not have a recognizable latent or asymptomatic stage.* * This statement is incorrect; a disease *must* have a **recognizable latent or asymptomatic stage** to be suitable for screening. * Screening aims to detect disease **before** symptoms appear, making the existence of such a stage essential for successful early intervention. *No effective treatment should exist for the disease.* * This statement is incorrect; for a screening program to be beneficial, an **effective treatment must exist** for the disease once detected. * Screening without effective treatment options would merely lead to earlier diagnosis without improving patient outcomes, causing unnecessary anxiety and burden.

Molecular Pathology Indian Medical PG Question 5: A patient has a cerebellar mass, renal tumor, and a family history of similar conditions. Which of the following mutations is most likely present in the family?

• A. VHL (Correct Answer)
• B. Neurofibromatosis (NF1)
• C. Tuberous Sclerosis Complex (TSC)
• D. Li-Fraumeni syndrome

Molecular Pathology Explanation: ***VHL*** - **Von Hippel-Lindau (VHL) disease** is an inherited disorder characterized by the development of tumors and cysts in various parts of the body, including **hemangioblastomas** in the cerebellum and retina, **renal cell carcinomas**, and pheochromocytomas [1]. - The combination of a **cerebellar mass**, renal tumor, and a family history strongly points to VHL disease, which is caused by a germline mutation in the **VHL tumor suppressor gene** [1]. *Neurofibromatosis (NF1)* - **Neurofibromatosis type 1 (NF1)** typically presents with multiple neurofibromas, **café-au-lait spots**, optic pathway gliomas, and Lisch nodules in the iris. - While NF1 can cause tumors, the specific combination of a cerebellar mass and renal tumor is not typical of NF1, and the characteristic skin findings are not mentioned. *Tuberous Sclerosis Complex (TSC)* - **Tuberous Sclerosis Complex (TSC)** is characterized by the growth of benign tumors in the brain (e.g., **subependymal giant cell astrocytomas**), kidneys (e.g., **angiomyolipomas**), heart, lungs, and skin (e.g., facial angiofibromas) [2]. - While TSC can involve brain and kidney tumors, the typical brain tumors are different (astrocytomas vs. hemangioblastomas), and hemangioblastomas are not a common feature of TSC [2]. *Li-Fraumeni syndrome* - **Li-Fraumeni syndrome** is a rare inherited cancer predisposition syndrome characterized by a high risk of developing various cancers, including **sarcomas**, breast cancer, brain tumors (often astrocytomas or medulloblastomas), and adrenocortical carcinoma. - While brain tumors are part of Li-Fraumeni syndrome, renal cell carcinoma is not a primary feature, and the classic cerebellar hemangioblastoma is not typical for this syndrome. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 724-727. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1318-1319.

Molecular Pathology Flashcard 1 of 5

Question: Which subtype under molecular classification of breast cancer has the best prognosis?_____

Answer: Luminal A

Molecular Pathology Flashcard 2 of 5

Question: Oncotype dx, mammaprint, endopredict and PAM50- Prosigna are all prognostic panels based on _____ in breast cancers

Answer: gene expression

Molecular Pathology Flashcard 3 of 5

Question: HER2-_____ cancers are most common subtype of breast cancer in patients with germline mutations in TP53 (Li Fraumeni syndrome)

Answer: positive

Molecular Pathology Flashcard 4 of 5

Question: _____ is a molecular test in breast cancer that is a 21-gene assay

Answer: Oncotype Dx

Molecular Pathology Flashcard 5 of 5

Question: In Array based Comparative Genomic Hybridization, if the test sample has amplification, then some spots on the array will flouresce _____.

Answer: red