# Risk of Recurrence and Cancer Stem Cell Marker CD133 Expression Vary in Males Versus Females with Papillary Thyroid Cancer

## TL;DR

This study finds that CD133 expression and recurrence risk in papillary thyroid cancer differ between males and females, with males having worse outcomes when CD133 levels are high.

## Contribution

The study reveals sex-specific differences in CD133's prognostic value for papillary thyroid cancer recurrence.

## Key findings

- CD133 H-score of 55 or higher predicted recurrence with 92% sensitivity.
- Males with high CD133 H-scores had significantly worse recurrence-free survival than females.
- CD133 expression did not significantly differ between patients with and without recurrence overall.

## Abstract

Molecular profiling has refined the identification of pathologic subtypes in other cancers, but is not currently used for prognostication in papillary thyroid cancer (PTC). The cancer stem cell marker, CD133, is a glycoprotein associated with tumor initiation and radioresistance in PTC, but its role in prognostication continues to be defined. This study sought to define the association between CD133 expression in PTC and recurrence-free survival (RFS).

All the patients at a single institution with PTC who underwent thyroidectomy from 2008 to 2011 were identified through an electronic medical record query. Immunohistochemistry was performed for CD133, and the H-score was calculated. Receive operating characteristic (ROC) curves were used to identify the optimal cutoff for CD133 expression.

Overall, 110 consecutive patients were identified, and 12% had a biopsy-proven recurrence during a median follow-up period of 10.1 years (interquartile range [IQR], 8.3–11.5 years). The median H-score did not differ significantly between the patients who experienced recurrence (74; IQR, 59–81) and those who did not (70; IQR, 51–89). An H-score of 55 or higher identified patients who had a recurrence with 92% sensitivity. Among the patients with a CD133 H-score of 55 or higher, males had a significantly worse RFS than females (p = 0.005), but RFS did not differ between males and females with a CD133 H-score lower than 55 (p = 0.739).

A clear role of CD133 in prognostication has not been defined to date. Expression of CD133 and its association with survival varies between males and females, with stratification of recurrence risk more prominent in males.

The online version contains supplementary material available at 10.1245/s10434-025-17256-2.