Nucleus YAP expression as a prognostic biomarker for local recurrence in eyelid sebaceous carcinoma

Abstract

Eyelid sebaceous carcinoma (SbC) is a rare malignancy characterized by potentially aggressive behavior and a high local recurrence rate. This study aims to investigate the expression of nuclear YAP and its clinicopathological correlation in eyelid SbC. In the patients with eyelid SbC who had available tumor specimens, nuclear YAP and androgen receptor (AR) expression were assessed using immunohistochemistry staining, quantified by histochemical scoring (H-score). The primary outcome was local recurrence-free survival (LRFS). Additionally, distant recurrence-free survival, recurrence-free survival, and overall survival were evaluated. Among 47 patients, local recurrence occurred in 10 cases (21.3%), and distant recurrence was observed in 4 cases (8.5%) over a median follow-up period of 39.5 months. All local recurrence events were observed in the low nuclear YAP group (H-score ≤ 90), with a 5-year LRFS of 66.2% among 36 patients. Additionally, lower AR expression (H-score ≤ 50) was linked to a decreased 5-year LRFS of 59.4%, compared to 82.6% in the high AR expression group (Hazard ratio, 3.43; 95% CI, 0.96-12.20; p = 0.043). Lower nuclear YAP and AR expression appear to be associated with high local recurrence rates. Nuclear YAP expression may serve as a promising biomarker for prognosticating local recurrence in eyelid SbC.

Keywords: Androgen receptor; Eyelid sebaceous carcinoma; Immunohistochemistry; Local recurrence; Nuclear YAP.

Fig. 1

Representative images of YAP expression in eyelid sebaceous carcinoma, stratified by nuclear YAP level. In the high nuclear YAP expression group, images include (A) H&E staining (x 200), YAP immunohistochemical staining (C) at low magnification (x 200), and (E) at high magnification (x 400). In the low nuclear YAP expression group, images include (B) H&E staining (x 200), YAP immunohistochemical staining (D) at low magnification (x 200), and (F) at high magnification (x 400). Clinical photographs of representative lesions are also shown: (G) high nuclear YAP case; (H) low nuclear YAP case.

Fig. 2

Kaplan-Meier curves stratified by nuclear YAP expression status comparing (A) local recurrence-free survival, (B) distant recurrence-free survival, (C) relapse-free survival, and (D) overall survival.

Fig. 3

Representative images of AR expression in eyelid sebaceous carcinoma, stratified by AR level. In the high nuclear AR expression group, images include (A) H&E staining (x 200), AR immunohistochemical staining (C) at low magnification (x 200), and (E) at high magnification (x 400). In the low AR expression group, images include (B) H&E staining (x 200), AR immunohistochemical staining (D) at low magnification (x 200), and (F) at high magnification (x 400). Clinical photographs of representative lesions are also shown: (G) high AR case; (H) low AR case.

Fig. 4

Kaplan-Meier curves stratified by AR expression status comparing (A) local recurrence-free survival, (B) distant recurrence-free survival, (C) relapse-free survival, and (D) overall survival.

Fig. 5

Kaplan-Meier curves stratified by both nuclear YAP and AR expression status comparing (A) local recurrence-free survival, (B) distant recurrence-free survival, (C) relapse-free survival, and (D) overall survival. ^†Hazard ratio (HR) was calculated between the AR low and AR high expression subgroups within the low nuclear YAP expression group. ^¶HR was calculated using Firth’s Penalized Cox Regression to reduce bias and provide stable estimates with limited sample size or event counts.