ACG 2026 Data Show TissueCypher® Identifies Elevated Risk of Progression Beyond Pathology Findings in Barrett's Esophagus

In the multi-center cohort, management recommendations changed consistently with TissueCypher risk classifications for 96% of patients.

Rhea-AI Summary

Castle Biosciences (CSTL) announced three TissueCypher studies evaluating molecular risk assessment in Barrett's esophagus for presentation at ACG 2026.

The research includes two case reports and a multi-center study. In the cohort, management recommendations changed consistently with TissueCypher risk classifications for 96% of patients. TissueCypher classified 83% as low risk and 17% as intermediate/high risk, versus 31% and 69%, respectively, with the Progression in Barrett's clinical and pathology-based approach. Agreement between the approaches was slight. Physicians recommended five-year surveillance for 38 patients and endoscopic treatment for eight. Both case reports described high-risk test results followed by detection of previously undetected high-grade dysplasia, an advanced precancerous change.

Positive

• Minor pointManagement recommendations changed consistently with TissueCypher risk classifications for 96% of patients in the multi-center cohort.
• Minor pointTissueCypher-guided recommendations extended surveillance to five years for 38 patients, versus generally three years under the comparison approach.
• Minor pointEndoscopic treatment was recommended for eight patients, including five without biopsy-detected dysplasia but intermediate/high TissueCypher risk.
• Minor pointA case with 62% five-year progression probability prompted repeat endoscopy at six months, identifying previously missed high-grade dysplasia.
• Minor pointA case with 47% five-year progression probability prompted intervention at two months; subsequent treatment achieved complete intestinal metaplasia eradication.

Negative

• None.

News Explained

In the case with discordant biopsies, a high-risk result on an “indefinite for dysplasia” sample was followed by RFA two months later; biopsies then confirmed HGD, and after RFA and subsequent cryotherapy, follow-up biopsies confirmed complete eradication of intestinal metaplasia.

Key Figures

Progression probability: 62% Progression probability: 47% Cohen's κ: 0.04 +5 more

Progression probability

62%

High-risk TissueCypher result; progression to HGD or EAC within five years

Progression probability

47%

High-risk TissueCypher result; progression to HGD or EAC within five years

Cohen's κ

0.04

Agreement between TissueCypher and PIB risk stratification

TissueCypher risk classification

83% low risk; 17% intermediate/high risk

Multi-center cohort

PIB risk classification

31% low risk; 69% intermediate/high risk

Multi-center cohort

Management recommendations changed

96%

In a manner consistent with TissueCypher risk classification

Longer surveillance recommendation

38 patients

Five-year surveillance window based on TissueCypher results

Endoscopic eradication therapy

8 patients

Recommended based on TissueCypher results

Historical Context

1 past event · Latest: Sep 28

1 event

1. Sep 28

   TissueCypher study

   24h Move

   +0.3%

   Prior 30-patient NDBE study reported recommendation changes or increased physician confidence for 97%.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

high-grade dysplasia, esophageal adenocarcinoma, histopathology, endoscopic eradication therapy, +1 more

5 terms

high-grade dysplasia medical

"probability of progression to high-grade dysplasia (HGD) or EAC within five years"

High-grade dysplasia is a severe abnormal change in cells of a tissue that looks much closer to cancer than normal cells and carries a high risk of becoming invasive cancer if not treated. For investors, it matters because diagnosis, treatment, or clinical trial results involving high-grade dysplasia can directly affect regulatory decisions, projected medical costs, market demand for therapies, and the commercial outlook for companies developing diagnostics or treatments—much like spotting deep cracks in a building that require urgent repair.

esophageal adenocarcinoma medical

"increased risk of esophageal adenocarcinoma (EAC)"

Esophageal adenocarcinoma is a form of cancer that begins in the gland-like cells lining the lower part of the esophagus, the tube that carries food to the stomach. It matters to investors because it is often aggressive and has limited treatment options, so advances, trial results, regulatory approvals, or changes in insurance coverage for new tests and therapies can materially affect the prospects and valuations of companies working on diagnostics, drugs, or procedures—like a bridge repair changing traffic for nearby businesses.

histopathology medical

"beyond histopathology to support risk-aligned patient management decisions"

Microscopic examination of tissue samples to identify disease, damage, or the effects of a treatment; pathologists slice, stain and study cells much like a mechanic inspects engine parts to find what’s broken. For investors, histopathology provides hard evidence about whether a drug, device or diagnostic actually works or causes harm, and those findings can strongly influence clinical outcomes, regulatory decisions and a company’s future value.

endoscopic eradication therapy medical

"underwent endoscopic eradication therapy (EET) with radiofrequency ablation (RFA)"

Endoscopic eradication therapy is a group of minimally invasive procedures that use a flexible tube with a camera to locate and remove or destroy abnormal tissue lining the digestive tract, often to stop precancerous changes from progressing. For investors, it signals markets for specialized medical devices, procedure revenues and reimbursement trends, and clinical outcomes that can affect adoption—think of it as removing embers before a small fire becomes catastrophic.

radiofrequency ablation medical

"endoscopic eradication therapy (EET) with radiofrequency ablation (RFA)"

A medical procedure that uses a thin probe to deliver controlled heat (radiofrequency energy) to destroy or disable problematic tissue, such as small tumors, overactive nerves, or abnormal heart pathways; think of it as applying a focused heat spot to stop a problem without large incisions. Investors care because the technique drives demand for specialized devices, affects treatment volumes, reimbursement rates, and regulatory approvals, all of which influence medical-device and healthcare company revenues.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Studies highlight how molecular risk assessment with TissueCypher can help inform surveillance and treatment decisions beyond biopsy findings alone

FRIENDSWOOD, Texas, Oct. 12, 2026 /PRNewswire/ -- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced that new data from three studies evaluating its TissueCypher Barrett's Esophagus (BE) test will be presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting and Postgraduate Course, taking place Oct. 9-14 in Nashville, Tennessee. The studies include two case reports and one multi-center study highlighting how TissueCypher can provide additional risk information beyond histopathology to support risk-aligned patient management decisions.

"Endoscopic biopsy findings do not always tell the whole story when it comes to a patient's risk of progression," said study author Virendra Joshi, M.D., FAGA, FACG, board-certified gastroenterologist and associate professor in the Division of Digestive Diseases in the Department of Medicine at Emory University School of Medicine in Atlanta. "The studies being presented at ACG demonstrate how TissueCypher can complement standard pathology by providing objective molecular risk information that helps guide surveillance and treatment decisions for patients with Barrett's esophagus, particularly when a patient's molecular risk suggests a different approach than their biopsy diagnosis alone would indicate."

BE is a precancerous condition associated with an increased risk of esophageal adenocarcinoma (EAC), yet biopsy findings alone do not always accurately reflect a patient's individual biological risk of progression. TissueCypher analyzes protein biomarkers and tissue architecture in routine endoscopic biopsy samples to provide an individualized five-year probability of progression to high-grade dysplasia (HGD) or EAC.

Study findings and presentation details are included below. All posters will be presented in Exhibit Halls A-D (Level 3) at Music City Center.

P3056: The Tissue Systems Pathology Test Enabled Detection of Missed Prevalent Dysplasia in a Presumed Clinically Low-Risk Patient With Non-Dysplastic Barrett's Esophagus

• Presenting author: Salih Samo, M.D., University of Kansas School of Medicine
• Date and Time: Monday, Oct. 12; 10:30 a.m.-4:15 p.m. Central time
• Key findings: According to gastroenterology society guidelines, patients diagnosed with non-dysplastic BE (NDBE) are generally recommended to undergo surveillance endoscopy every three to five years because they are considered at relatively low risk of progression. However, biopsy findings alone may not fully reflect a patient's underlying biological risk, and some patients may harbor advanced precancerous changes that cannot be detected through routine histopathologic assessment alone. In this case report, TissueCypher returned a high-risk result for a patient with NDBE, indicating a 62% probability of progression to HGD or EAC within five years. The result informed a risk-based management approach and led to a repeat endoscopy six months after the initial examination, at which previously missed prevalent HGD was identified. The patient subsequently underwent endoscopic eradication therapy (EET) with radiofrequency ablation (RFA). This case illustrates how TissueCypher may help identify elevated risk among patients with an NDBE diagnosis, helping clinicians identify patients who may benefit from earlier evaluation and intervention than would otherwise be recommended based on histology alone.

P5192: Real-World Impact of Tissue Systems Pathology Test on Barrett's Esophagus Management: A Multi-Center Cohort Study

• Presenting author: Shree Patel, M.D., Emory University School of Medicine
• Date and Time: Tuesday, Oct. 13; 10:30 a.m.-4 p.m. Central time
• Key findings: Histopathology and clinical factors alone may not fully identify which patients with BE are at elevated risk of progression to HGD/EAC. In the study, molecular risk stratification using TissueCypher was compared with the Progression in Barrett's (PIB) clinicopathologic-based risk stratification approach. There was only slight agreement between the two approaches (Cohen's κ = 0.04). TissueCypher classified 83% of patients as low risk and 17% as intermediate/high risk, whereas the PIB score classified 31% of patients as low risk and 69% as intermediate/high risk. Following TissueCypher testing, management recommendations were changed in a manner consistent with the test's risk classification for 96% of patients in this cohort, suggesting that the results informed clinical decision-making in this study population. Under guideline-informed management, most patients would have been recommended surveillance every three years using the PIB approach. However, guided by TissueCypher results, physicians recommended a longer five-year surveillance window for 38 patients and EET for eight, which included five patients with NDBE whose TissueCypher results indicated intermediate or high risk or progression despite having no dysplasia detected on their biopsy. These findings suggest that TissueCypher may provide additional risk information beyond clinicopathologic assessment to support more individualized surveillance and treatment recommendations.

P5296: The Tissue Systems Pathology Test Facilitated Early Intervention in a Histopathologically Complex Case of Barrett's Esophagus

• Presenting author: Shree Patel, M.D., Emory University School of Medicine
• Date and Time: Tuesday, Oct. 13; 10:30 a.m.-4 p.m. Central time
• Key findings: Conflicting biopsy results can make it difficult to determine the appropriate management strategy for patients with BE. In this case, a patient's biopsies were successively classified as NDBE, low-grade dysplasia (LGD) and indefinite for dysplasia (IND), creating uncertainty about the patient's risk and management plan. TissueCypher testing of the IND biopsy returned a high-risk result, indicating a 47% probability of progression to HGD or EAC within five years. The high-risk result prompted an interventional endoscopy with RFA two months after the endoscopy that yielded the IND diagnosis. Biopsies obtained during the procedure confirmed previously undetected HGD, consistent with the TissueCypher high-risk classification. Following RFA and subsequent cryotherapy, follow-up biopsies confirmed complete eradication of the patient's intestinal metaplasia. This case illustrates how TissueCypher may help reduce uncertainty for patients with inconclusive or discordant biopsy findings by providing objective risk information that supports timely intervention and individualized patient management.

TissueCypher Product Theater

• Date and Time: Tuesday, Oct. 13; 1:15-1:45 p.m. Central time 
• Location: Product Theater Area (Booth 117)
• Castle will host a product theater titled, "Low-risk on histology. High-risk in reality: Johnny Walker's journey with Barrett's esophagus." During the session, TissueCypher patient ambassador Johnny Walker will join Mark Amorosino, M.D., gastroenterologist at Gastro Health, and David Forcione, M.D., advanced endoscopist at Baptist Health, to discuss how TissueCypher's molecular risk assessment provided additional insight beyond his NDBE diagnosis and informed treatment decisions that ultimately led to the detection of dysplasia.

For more information on TissueCypher, visit Castle at Booth 1706.

About TissueCypher Barrett's Esophagus Test
TissueCypher is a precision medicine test designed and extensively validated to predict a patient's personalized risk of progression from Barrett's esophagus (BE) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Indicated for patients with non-dysplastic BE, indefinite for dysplasia or with low-grade dysplasia, TissueCypher's five-year risk assessment is designed to help physicians tailor care to each patient's risk of developing HGD or EAC.

Backed by more than 17 peer-reviewed publications and studied in biopsies from more than 8,000 patients, TissueCypher has been shown to be the strongest independent predictor of progression compared with traditional histopathological risk assessment. Using an AI-derived spatialomics approach, the test identifies molecular signatures that often precede the development of dysplasia, which can enable earlier identification, treatment, and management of patients at increased risk of cancer. TissueCypher is designed to integrate seamlessly into routine endoscopic practice by analyzing standard esophageal pinch biopsies, delivering actionable insights without requiring additional procedures. Learn more at CastleBiosciences.com/TissueCypher.

About Castle Biosciences
Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. With a primary focus in dermatologic and gastroenterological disease, we develop personalized, clinically actionable solutions that help improve disease management and patient outcomes.

We put people first—empowering patients and clinicians and informing care decisions through rigorous science and advanced molecular tests that support more confident treatment planning. To learn more, visit www.CastleBiosciences.com and connect with us on LinkedIn, Instagram, Facebook and X. 

DecisionDx-Melanoma, DecisionDx-CMSeq, i31-SLNB, i31-ROR, DecisionDx-SCC, MyPath Melanoma, AdvanceAD-Tx, TissueCypher, Esopredict, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc.

Forward-Looking Statements 
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the "safe harbor" created by those sections. These forward-looking statements include, but are not limited to, statements concerning: TissueCypher's ability to (i) predict a patient's personalized risk of progression from Barrett's esophagus to high-grade dysplasia or esophageal adenocarcinoma, (ii) help clinicians tailor surveillance and management decisions to each patient's individual risk profile, (iii) enable earlier identification and management of patients at increased risk of cancer, (iv) help reduce uncertainty for patients, and (v) perform favorably as compared with traditional histopathological risk assessment and integrate into routine clinical workflows. The words "believe," "can," "may" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results obtained in these studies, including with respect to the discussion of our tests in this press release; actual application of our tests may not provide the aforementioned benefits to patients; and the risks set forth under the heading "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2025, and our subsequent Quarterly Reports on Form 10-Q, each as filed or to be filed with the SEC, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law.

Investor Contact:
Camilla Zuckero
czuckero@castlebiosciences.com

Media Contact:
Allison Marshall
amarshall@castlebiosciences.com

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SOURCE Castle Biosciences, Inc.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Castle Biosciences' TissueCypher multi-center study show at ACG 2026?

Management recommendations changed consistently with TissueCypher risk classifications for 96% of patients in the cohort. Physicians recommended five-year surveillance for 38 patients and endoscopic eradication therapy for eight. TissueCypher and the Progression in Barrett's clinical and pathology-based approach showed only slight agreement, with Cohen's κ = 0.04, a measure of agreement.

What happened in Castle Biosciences' TissueCypher case involving conflicting Barrett's esophagus biopsies?

A high-risk TissueCypher result prompted an interventional endoscopy with radiofrequency ablation two months after an inconclusive biopsy diagnosis. Biopsies during the procedure confirmed previously undetected high-grade dysplasia. Following ablation and subsequent cryotherapy, follow-up biopsies confirmed complete eradication of intestinal metaplasia, the abnormal tissue change associated with Barrett's esophagus.