Login to Access Video or Poster Abstract: MP80-17
Sources of Funding: none

Introduction

In testicular germ cell tumors (GCT) attempts have been made to stratify patients, who are at higher risk for disease recurrence based on certain pathological characteristics or biomarkers. Recently Gilbert et al. (Clin Cancer Res 2016) described an association between immunohistochemical CXCL12 expression and a decreased relapse rate in stage 1 non-seminoma patients. Therefore CXCL12 might be a clinically useful biomarker to allocate patients with stage 1 non-seminoma to adjuvant therapy vs. active surveillance. The aim of our study was to externally validate the results of Gilbert et al. and to assess the utility of CXCL12 as prognostic marker in patients with metastatic disease.

Methods

A tissue micro array was constructed with tissue cores of 152 seminoma, 113 non-seminoma and 14 non-cancer patients, diagnosed in the period from 2004-2014. All tumor components were represented by two tissue cores (diameter 0.6 mm). If more than one tumor component was present in case of non-seminoma, each component was separately punched and represented on the tissue microarray. Immunohistochemical staining of TMA sections with CXCL12 antibody (Antibody 79018, 1:100; R&D Systems) was performed. The amount and the intensity of positive stained cells were analyzed using a semi-quantitative score.

Results

Of 267 GCT patients, 31 out of 153 (20.3%) seminoma and 54 out of 114 (47.3%) non-seminoma patients were diagnosed with metastatic disease. Within all 1201 tissue cores CXCL12 expression was found in 0.2% of seminomatous components, 88.2% of yolk sac tumors, 43.3% of teratomas, 100% of choriocarcinomas, 30.6% of embryonal carcinoma, 0% of Germ cell neoplasia in situ (GCNIS) and 0% in normal tissue. With focus on non-seminoma patients, CXCL12 was expressed in 30 out of 60 (50%) localized and 27 out of 54 (50%) metastatic patients._x000D_ After a median follow-up of 5.2 years (IQR 3.2-8.5) follow-up was available for 260 patients (98%) of which 36 (13.8%) recurred. In localized non-seminoma patients 7 out of 29 (24.1%) CXCL12 positive patients recurred compared to 4 out of 23 (14.8%) CXCL12 negative patients (p=0.506). In metastatic non-seminoma patients 11 out of 12 (91.7%) CXCL12 positive patients compared to 1 out of 25 (4.0%) CXCL12 negative patients showed disease relapse after initial chemotherapy (p=0.001).

Conclusions

CXCL12 is almost exclusively expressed in non-seminoma and absent in seminoma, normal tissue or GCNIS. The reported association between CXCL12 expression and lower recurrence rates in stage 1 non-seminoma patients could not be reproduced in our dataset. However our analysis suggests that CXCL12 expression is a risk factor for recurrence in metastatic non-seminoma patients.

Funding

none