Surreal illustration of the connection between gastrointestinal health and molecular diagnostics.

Decoding Gastrointestinal Cancer: How Molecular Testing is Changing Everything

Lena Kashyap in Health & Wellness July 2025 • 4 min read.

"A guide to understanding the latest advancements in molecular testing for gastric and colorectal cancers, and how they're impacting diagnosis, treatment, and prognosis."

Gastrointestinal (GI) cancers, including gastric (GC) and colorectal (CRC) cancers, remain a significant health challenge worldwide. While traditionally diagnosed and treated based on broad characteristics, the past two decades have seen a revolution in our understanding of these diseases at the molecular level. This understanding is translating into more precise diagnostic tools and targeted therapies.

Molecular testing, which analyzes the unique genetic and molecular fingerprints of a tumor, is now a critical part of managing GI cancers. These tests help identify inherited risks, predict how a cancer will behave, and determine which treatments are most likely to be effective. This personalized approach offers the potential to significantly improve patient outcomes.

This article explores the current landscape of molecular testing for GI cancers, focusing on gastric and colorectal adenocarcinoma. We'll delve into key molecular markers, their clinical significance, and how they're guiding treatment decisions. We'll also discuss the importance of standardized testing methods and quality control to ensure reliable results, empowering patients and healthcare professionals alike.

The Power of Molecular Testing: Key Markers & Their Impact

Surreal illustration of the connection between gastrointestinal health and molecular diagnostics.

Molecular testing has moved beyond simply identifying the type of cancer to providing a detailed roadmap of its individual characteristics. Here's a look at some key markers and their clinical implications:

Microsatellite Instability (MSI): MSI analysis screens for Lynch syndrome, predicts prognosis, and identifies immunotherapy candidates. MSI-High (MSI-H) cancers often have:

Better overall survival.

Distinct subtypes with elevated mutation rates.

Association with specific immune checkpoint molecules.

MSI-H status is also linked to favorable treatment with immune checkpoint inhibitors, making MSI testing crucial for personalized treatment strategies.

HER2 Testing: Essential for advanced gastric cancers, HER2 testing determines eligibility for trastuzumab, a targeted therapy. Accurate HER2 assessment requires:

Immunohistochemistry (IHC) as a first step.

In situ hybridization (FISH or SISH) for equivocal IHC results.

Careful consideration of intratumoral heterogeneity.

RAS and BRAF Mutations: In colorectal cancer, RAS (KRAS and NRAS) mutation testing predicts resistance to EGFR inhibitors. BRAF mutations can indicate poorer prognosis. These mutations guide treatment decisions and offer prognostic information.

The Pathologist's Pivotal Role: Ensuring Accurate and Reliable Results

The complexity of molecular testing requires expertise to ensure accurate and reliable results. Pathologists play a crucial role in:<li>Specimen selection.</li><li>Test validation.</li><li>Data interpretation.</li>

With their knowledge of cancer biology and molecular techniques, pathologists bridge the gap between laboratory findings and clinical decision-making. Their expertise ensures that molecular testing is used effectively to guide personalized treatment strategies.

As molecular testing continues to evolve, ongoing research and standardized quality control measures are essential. Collaboration between pathologists, oncologists, and molecular laboratories will drive further progress, ultimately improving outcomes for patients with gastrointestinal cancers.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.4132/jptm.2017.01.24, Alternate LINK

Title: Molecular Testing For Gastrointestinal Cancer

Subject: Histology

Journal: Journal of Pathology and Translational Medicine

Publisher: The Korean Society of Pathologists and The Korean Society for Cytopathology

Authors: Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y. Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho

Published: 2017-03-15

Everything You Need To Know

What is molecular testing and why is it important for Gastrointestinal (GI) cancers?

Molecular testing analyzes a tumor's unique genetic and molecular makeup. Its significance lies in providing a detailed understanding of the cancer, moving beyond broad classifications. This detailed roadmap informs diagnosis, predicts cancer behavior, and guides treatment decisions. The implications are improved patient outcomes through personalized treatment strategies.

What does MSI testing involve and why is it important?

MSI analysis identifies Microsatellite Instability (MSI) status. MSI-High (MSI-H) cancers, as opposed to Microsatellite Stable cancers, are associated with a better overall survival rate and often respond well to immunotherapy. MSI testing is crucial because it helps identify patients who may benefit from specific treatments, like immune checkpoint inhibitors, and also helps predict prognosis in Gastric Cancer (GC) and Colorectal Cancer (CRC).

What is HER2 testing and why is it significant?

HER2 testing determines whether a patient with advanced gastric cancer is eligible for trastuzumab, a targeted therapy. The importance of this test is to provide an effective therapy for certain patients. Accurate HER2 assessment involves Immunohistochemistry (IHC) as a first step, followed by in situ hybridization (FISH or SISH) for uncertain IHC results. Incorrect testing can deny patients effective treatment.

How do RAS and BRAF mutations influence treatment decisions in Colorectal Cancer (CRC)?

RAS (KRAS and NRAS) mutation testing in Colorectal Cancer (CRC) is essential because it helps predict whether a patient will be resistant to EGFR inhibitors. BRAF mutations can indicate a poorer prognosis. These tests direct treatment decisions and provide valuable prognostic information. Understanding these mutations allows oncologists to tailor treatment plans for each patient.

What is the role of a pathologist in the context of molecular testing?

Pathologists ensure the accuracy and reliability of molecular testing. Their role includes specimen selection, test validation, and data interpretation. Their expertise is vital due to the complexity of these tests. Without the pathologist's careful work, the potential benefits of molecular testing could not be achieved.