Inter-assay reliability of programmed cell death-ligand 1 in head and neck squamous cell carcinoma.

OBJECTIVES: The programmed cell death-ligand 1 (PD-L1) 22C3 pharmDx assay is used as a companion diagnostic test to select head and neck squamous cell carcinoma (HNSCC) patients that may benefit from treatment with the checkpoint inhibitor pembrolizumab. Because the Dako platform is not universally available, we studied the performance of a 22C3 laboratory developed test (LDT) performed on a Ventana BenchMark Ultra compared to the 22C3 pharmDx assay. MATERIALS AND METHODS: Serial sections from tissue micro arrays (TMAs) containing tumour tissue from 97 HNSCC patients were stained with the 22C3 pharmDx assay and 22C3 LDT. All TMA cores were scored by three dedicated head and neck pathologists for PD-L1 expression. RESULTS: Substantial interobserver agreement was reported for both the standardized 22C3 pharmDx assay and the 22C3 LDT (respectively Fleiss' κ 0.62, 95% CI 0.57-0.67 and 0.63, 95% CI 0.58-0.68). Concordance between the assays was almost perfect on core and patient level (respectively Weighted κ 0.84, 95% CI 0.79-0.89 and 0.84, 95% CI 0.75-0.92). Intratumor heterogeneity between the cores per patient case was similar in both assays. CONCLUSION: After validation a 22C3 LDT is non-inferior to the standardized 22C3 pharmDx assay and can be safely used to select HNSCC patients for pembrolizumab treatment.

Differences in cancer gene copy number alterations between Epstein-Barr virus-positive and Epstein-Barr virus-negative nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) treatment is mainly based on clinical staging. We hypothesize that better understanding of the molecular heterogeneity of NPC can aid in better treatment decisions. Therefore, the purpose of this study was to present our exploration of cancer gene copy-number alterations (CNAs) of Epstein-Barr virus (EBV)-positive and EBV-negative NPC. METHODS: Multiplex ligation-dependent probe amplification was applied to detect CNAs of 36 cancer genes (n = 103). Correlation between CNAs, clinicopathological features, and survival were examined. RESULTS: The CNAs occurred significantly more in EBV-negative NPC, with PIK3CA and MCCC1 (P < .001) gain/amplification occurring more frequently. Gain/amplification of cyclin-L1 (CCNL1) and PTK2 (P < .001) predict worse disease-free survival (DFS) in EBV-positive NPC. CONCLUSION: The EBV-positive and EBV-negative NPC show some similarities in cancer gene CNAs suggesting a common pathogenic route but also important differences possibly indicating divergence in oncogenesis. Copy number gain/amplification of CCNL1 and PTK2 are possibly good predictors of survival in EBV-positive NPC.

Differences in T-cell infiltrates and survival between HPV+ and HPV- oropharyngeal squamous cell carcinoma.

Recent studies have suggested that immune cells as part of tumor's microenvironment could partly explain the better outcome in HPV-associated oropharyngeal carcinoma. We performed a systematic review of the literature focused on differences in immune-infiltrate in HPV+ versus HPV- oropharyngeal cancers. This comprehensive search yielded 4308 original papers, of which 20 satisfied our eligibility criteria. Increase in both circulating and tumor infiltrating CD8+ lymphocytes is mainly seen in HPV+ oropharyngeal carcinoma. Interestingly, the survival benefit associated with increase in immune cells is equal both in HPV+ and HPV- oropharyngeal cancer. Based on these results, our review underscores the role of the immune system in the biological and clinical behavior of oropharyngeal squamous cell carcinomas (OPSCC) and might open doors to further investigate immune modulatory treatment options in OPSCC patients.

Poor prognosis in human papillomavirus-positive oropharyngeal squamous cell carcinomas that overexpress hypoxia inducible factor-1α.

BACKGROUND: Hypoxia induces stabilization of the transcription factor HIF-1alpha (HIF-1α), associated with (chemo-)radiotherapy resistance in oropharyngeal squamous cell carcinoma (SCC). We investigated the effect of HIF-1α expression on survival in relation to human papillomavirus (HPV) status in oropharyngeal SCC. METHODS: We conducted an immunohistochemical analysis of HIF-1α protein expression and downstream targets carbonic anhydrase-IX (CA-IX) and glucose transporter-1 (GLUT-1) in 274 patients with oropharyngeal SCC. Overall survival (OS) was analyzed in total and stratified for HPV status and treatment. RESULTS: In HPV-positive tumors (n = 44), HIF-1α overexpression predicted worse OS (hazard ratio [HR] = 6.23; p = .012), whereas TNM classification or treatment modality did not. In HPV-negative tumors (n = 218), advanced T and N classification and HIF-1α overexpression all independently predicted worse OS. However, the effect of HIF-1α overexpression on OS was lower in HPV-negative (HR = 1.50; p = .024) than in HPV-positive tumors. CONCLUSION: HIF-1α overexpression is associated with worse OS and characterized a subgroup of patients with HPV-positive oropharyngeal SCC with poor prognosis. Possibly, patients with HIF-1α overexpressing HPV-positive tumors should not be eligible for treatment dose deescalation. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1338-1346, 2016.

Macroscopic hematuria in patient with myelofibrosis caused by extramedullary hematopoiesis of bladder.

Extramedullary hematopoiesis (EMH) is a physiologic process in fetal life. However, after birth, its occurrence is abnormal, and it develops when hematopoiesis in the bone marrow is disturbed, such as occurs in many hematologic disorders. EMH can become symptomatic, depending on its extent and location. We describe the case of a 67-year-old man with postpolycythemic myelofibrosis who presented clinically with macroscopic hematuria due to EMH in the bladder. EMH in the bladder is extremely rare but illustrates the importance of an adequate pathologic assessment of transurethral resection chips, especially in patients with underlying disease.