# CDX2 Expression and Fluoropyrimidine Response in Rare Non-GI Tumors: A Three-Case Series

## TL;DR

This study shows that CDX2, a protein typically used to identify intestinal tumors, may also predict response to certain chemotherapy in rare cancers.

## Contribution

The study suggests CDX2 could be a novel biomarker for fluoropyrimidine response in rare non-GI tumors.

## Key findings

- Three patients with rare metastatic cancers showed strong CDX2 expression and responded well to fluoropyrimidine-based chemotherapy.
- CDX2-positive tumors achieved marked metabolic and clinical responses, including a sustained complete metabolic response in one case.
- CDX2 may identify tumors susceptible to fluoropyrimidines regardless of their anatomical origin.

## Abstract

CDX2 is a protein normally expressed in intestinal cells and is widely used by pathologists to help determine the origin of tumors. However, CDX2 may also carry important therapeutic information. In this study, we describe three patients with rare metastatic cancers of the prostate, salivary gland, and sinonasal tract whose tumors strongly expressed CDX2, indicating an intestinal-like phenotype. Standard treatments were ineffective or not well established in these cases. Based on CDX2 expression, patients were treated with chemotherapy typically used for colorectal cancer. All three experienced substantial clinical and radiologic improvement. These cases suggest that CDX2 may serve not only as a diagnostic marker but also as a potential biomarker warranting further evaluation for treatment selection across different cancer types, particularly in rare tumors where evidence-based systemic options are limited.

Caudal type homeobox 2 (CDX2) is an intestine-specific transcription factor that serves as a diagnostic marker of enteric differentiation and may also reflect tumor behavior and therapeutic susceptibility. Emerging evidence suggests that CDX2 expression may predict sensitivity to fluoropyrimidine-based therapy independent of tissue of origin. We report a retrospective case series of three patients with metastatic adenocarcinoma (aggressive variant prostate, minor salivary gland, and intestinal-type sinonasal tract) exhibiting strong CDX2 nuclear expression. In all cases, tumors were refractory to or lacked established standard systemic therapy. Treatment decisions were informed by the CDX2-positive enteric phenotype, leading to the initiation of fluoropyrimidine-based regimens. Response was assessed using PET-CT and MRI. All three patients achieved marked metabolic and clinical responses, including a sustained complete metabolic response in the prostate cancer case and durable disease control in the salivary gland and sinonasal tumors. These findings highlight CDX2 as a potential biomarker requiring validation, which may identify tumors intrinsically susceptible to fluoropyrimidines regardless of anatomical origin. CDX2 immunohistochemistry is widely available and inexpensive, and may complement genomic profiling in rare malignancies or in settings where standard treatment algorithms are limited. This report is hypothesis-generating and not intended to estimate response rates or treatment efficacy.