Prognostic Impact of CD36 Immunohistochemical Expression in Patients with Muscle-Invasive Bladder Cancer Treated with Cystectomy and Adjuvant Chemotherapy

Abstract

Neoadjuvant chemotherapy followed by a cystectomy is the standard treatment in muscle-invasive bladder cancer (MIBC). However, the role of chemotherapy in the adjuvant setting remains controversial, and therefore new prognostic and predictive biomarkers are needed to improve the selection of MIBC patients. While lipid metabolism has been related to several biological processes in many tumours, including bladder cancer, no metabolic biomarkers have been identified as prognostic in routine clinical practice. In this multicentre, retrospective study of 198 patients treated with cystectomy followed by platinum-based adjuvant chemotherapy, we analysed the immunohistochemical expression of CD36 and correlated our findings with clinicopathological characteristics and survival. CD36 immunostaining was positive in 30 patients (15%) and associated with more advanced pathologic stages (pT3b-T4; p = 0.015). Moreover, a trend toward lymph node involvement in CD36-positive tumours, especially in earlier disease stages (pT1-T3; p = 0.101), was also observed. Among patients with tumour progression during the first 12 months after cystectomy, disease-free survival was shorter in CD36-positive tumours than in those CD36-negative (6.51 months (95% CI 5.05-7.96) vs. 8.74 months (95% CI 8.16-9.32); p = 0.049). Our results suggest an association between CD36 immunopositivity and more aggressive features of MIBC and lead us to suggest that CD36 could well be a useful prognostic marker in MIBC.

Keywords: CD36; MIBC; adjuvant chemotherapy; bladder cancer; fatty acid; lipid metabolism; prognostic biomarker.

Figure 1

Flow chart showing patient inclusion in the study. ICO-HUGTiP, Institut Català d’Oncologia-Hospital Universitari Germans Trias i Pujol (Badalona, Barcelona); H12 Octubre, Hospital 12 de Octubre (Madrid); HRyC, Hospital Ramon y Cajal (Madrid); IVO, Instituto Valenciano de Oncología (Valencia).

Figure 2

CD36 immunostaining in TMA samples. Most cases showed a diffuse linear membranous positivity with some cytoplasmic positivity as shown in these images from two different cases ((A): 10×; (B): 20×). In some tumours, immunoreactivity was heterogeneous (with positive and negative tumoral cells) ((C): 10×), and in a single case, we saw an additional dot-like pattern ((D): 20×).

Figure 3

CD36 immunoreactivity in whole sections. Heterogenous positivity was evident in both cystectomy ((A): H-E 4×; (B): CD36 4×) and lymph node whole sections ((D): H-E 20×; (E): CD36 20×) with membranous positivity with/without additional cytoplasmic positivity ((C,F), 40×). There were positive and negative tumoral areas in both superficial and deep parts of the tumour in the bladder wall (arrows in (B)) (All of these images are from the same case).

Figure 4

CD36 immunopositivity was significantly associated with greater depth of tumour invasion (pT3b-pT4 stage) (p = 0.015) (A) and showed a trend toward association with greater lymph node involvement (pN stage) (p = 0.391) (B), which was strongest in patients with earlier stage disease (pT1-T3) (p = 0.101) (C).

Figure 5

Kaplan Meier survival curve in the subgroup of patients with worse prognosis, identified as those who progressed during the first 12 months after RC, CD36-positive patients had shorter median PFS than CD36-negative patients (6.51 months (95% CI 5.05–7.96) vs 8.74 months (95% CI 8.16–9.32), respectively; (p = 0.049).