Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare Epstein-Barr virus (EBV) associated cancer, histologically indistinguishable from nasopharyngeal carcinoma (NPC). Somatostatin receptor type 2 (SSTR2) is a bonafide theranostic target in neuroendocrine tumour. It is also demonstrably expressed in NPC, with autoradiography and positron emission tomography (PET). SSTR2 expression has not been reported in PLELC. In this study, we aimed to investigate SSTR2 expression and its co-localization with EBV positive PLELC cells using immunohistochemistry (IHC); and to investigate the clinical significance of SSTR2 in PLELC.
Clinical demographics including age, gender, TNM staging, EBV titre, smoking status, survival and treatment regime were collected. Archival formalin fixed, paraffin embedded (FFPE) tissue from patients diagnosed with PLELC between 2003 and 2016 at National Cancer Centre Singapore were retrieved and studied retrospectively. IHC staining for SSTR2 and Epstein-Barr encoding region in-situ hybridisation (EBER-ISH) were performed using a dual-staining technique.
We report clinical data and dual staining from 20 PLELC patients. The median age at diagnosis was 56.5; 80% (16/20) of the patients were female; all non-smokers (except 3 with unknown status); 55% (11/20) of the patients had stage IV disease and the rest stage I-IIIB. High serum EBV titres were also noted in PLELC patients. Sixteen out of 20 patients (80%) stained positive for SSTR2 on IHC. SSTR2 expression co-localised with EBER positive cells. Nine out of 11 (82%) patients with stage IV PLELC stained positive for SSTR2 while 7 out of 9 (78%) stage I-III disease stained positive. Two year OS by SSTR2 status is 100% in SSTR2 negative and 65.2% (CI 35.1, 84.0) in SSTR2 positive patients, p = 0.467 by Log Rank Test. Two year OS by stage is 85.7% (CI 33.4, 85.7) for stage I-III and 63.6% (CI 29.7, 84.5) for stage IV disease, p = 0.014.
In PLELC, high levels of SSTR2 IHC expression is reported with co-localisation with EBV infected cells. A high proportion of stage IV patients have SSTR2 positive tumours. These patients have limited treatment options. This study opens up the possibility of using SSTR2 theranostics for these patients.
Clinical trial identification
Legal entity responsible for the study
National Cancer Centre Singapore.
National Cancer Centre Singapore Research Fund.
All authors have declared no conflicts of interest.