Incidence rate trends of histological subtypes of nasopharyngeal carcinoma in Hong Kong

The overall decline in incidence rate of nasopharyngeal carcinoma in Hong Kong during 1988–2002 was limited primarily to a decrease in keratinising carcinoma, which could be explained by the decline in cigarette smoking. Genetic and Epstein–Barr virus interactions may explain the relatively stable incidence rate of non-keratinising carcinoma

Chemotherapy-Induced Neuronal Maturation in Sinonasal Teratocarcinosarcoma—a Unique Observation

Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly malignant tumour with combined features of a teratoma and carcinosarcoma. We report the first case of a SNTCS in 23 year old male treated with neo-adjuvant chemotherapy followed by cranio-facial resection. The resection specimen displayed cellular maturation in the neuroectodermal component. The patient presented with a short history of nasal obstruction, epistaxis and headache. On imaging, a bone destroying lesion of left paranasal sinuses and nasal cavity was identified. The diagnosis of SNTCS could be offered only on the third biopsy which showed heterogeneous admixture of primitive neuroectodermal, epithelial and mesenchymal elements. An adequate sampling with high index of suspicion is needed to catch hold this rare tumor. Tumor was excised after 4 cycles of neo-adjuvant chemotherapy. On microscopic examination, it showed similar epithelial and mesenchymal components as the pretreatment biopsies. However, the primitive neuroectodermal component displayed extensive neuronal maturation. The undifferentiated neuroectodermal cells were completely absent in the post chemotherapy specimen. This case throws light on the morphologic evidence of chemotherapy induced maturation in the neuroectodermal component within SNTCS, an event hitherto not reported in the literature in case of SNTCS

Syndecan-1 expression has prognostic significance in head and neck carcinoma

The syndecans are a family of cell-surface heparan sulphate proteoglycans that regulate cell behaviour by binding extracellular matrix molecules such as growth factors. The syndecan family has four members, of which syndecan-1 is the most studied and best characterized. We have studied the prognostic significance of syndecan-1 expression in squamous cell carcinoma (SCC) of the head and neck treated with surgery and post-operative radiotherapy. Paraffin-embedded tissue samples taken from 175 patients with primary SCC, followed up from 2 to 15 years after surgery, were studied for expression of syndecan-1 by immunohistochemistry. A low number (≤50%, the median value) of syndecan-1-positive tumour cells was associated with low histological grade of differentiation (P < 0.0001), a large primary tumour size (T1–2 vs T3–4, P = 0.02), positive nodal status (N0 vs N1–3, P = 0.0006), and high clinical stage (stage I or II vs III or IV, P < 0.0001). Low syndecan-1 expression was also associated with unfavourable overall survival in a univariate analysis (P = 0.001). In a multivariate survival analysis, the clinical stage and syndecan-1 expression were the only independent prognostic factors. We conclude that syndecan-1 is a novel prognostic factor in SCC of the head and neck treated with surgery and post-operative radiotherapy. © 1999 Cancer Research Campaig

S-100 protein positive cells in nasopharyngeal carcinoma (NPC): absence of prognostic significance. A clinicopathological and immunohistochemical study of 40 cases

An immunohistochemical study of S-100 protein in 43 nasopharyngeal carcinomas (NPC) of known clinical evolution (33 primary and 10 metastatic) is presented. Sixty per cent of primary site cases as well as all metastatic forms showed S-100 protein positive cells intermingled with tumour cells. These S-100 positive elements were identified as Langerhans cells. No significant differences were found when correlating S-100 protein positivity and histological NPC variants, neither in age nor in sex of patients. Statistical analysis failed to demonstrate any positive correlation between S-100 protein reactivity and clinical survival

Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies

Epstein-Barr virus (EBV) is a gamma herpesvirus that causes a life-long latent infection in human hosts. The latent gene products LMP1, LMP2A and EBNA1 are expressed by EBV-associated tumors and peptide epitopes derived from these can be targeted by CD8 Cytotoxic T-Lymphocyte (CTL) lines. Whilst CTL-based methodologies can be utilized to infer the presence of specific latent epitopes, they do not allow a direct visualization or quantitation of these epitopes. Here, we describe the characterization of three TCR-like monoclonal antibodies (mAbs) targeting the latent epitopes LMP1[subscript 125–133], LMP2A[subscript 426–434] or EBNA1[subscript 562–570] in association with HLA-A0201. These are employed to map the expression hierarchy of endogenously generated EBV epitopes. The dominance of EBNA1[subscript 562–570] in association with HLA-A0201 was consistently observed in cell lines and EBV-associated tumor biopsies. These data highlight the discordance between MHC-epitope density and frequencies of associated CTL with implications for cell-based immunotherapies and/or vaccines for EBV-associated disease

Quantification of Epstein-Barr virus DNA load, interleukin-6, interleukin-10, transforming growth factor-β1 and stem cell factor in plasma of patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among the Chinese populations in Southern China and South East Asia. Epstein-Barr virus (EBV) is known to be an important etiologic agent of NPC and the viral gene products are frequently detected in NPC tissues along with elevated antibody titres to the viral proteins (VCA and EA) in a majority of patients. Elevated plasma EBV DNA load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the levels of certain interleukins and growth factors have also been implicated in NPC. The objectives of the present study are, 1) to investigate the correlations between plasma EBV DNA load and the levels of interleukin (IL)-6, IL-10, TGF-β1 and SCF (steel factor) and 2) to relate these parameters to the stages of NPC and the effect of treatment. METHODS: A total of 78 untreated NPC patients were enrolled in this study. Of these, 51 were followed-up after treatment. The remaining patients had irregular or were lost to follow-up. Plasma EBV DNA was quantified using real-time quantitative PCR. The levels of plasma interleukins and growth factors were quantified using ELISA. RESULTS: A significant decrease in EBV DNA load was detected in plasma of untreated NPC patients (1669 ± 637 copies/mL; n = 51) following treatment (57 ± 37 copies/mL, p < 0.05); n = 51). Plasma EBV DNA load was shown to be a good prognosticator for disease progression and clinical outcome in five of the follow-up patients. A significant difference in IL-6 levels was noted between the untreated patients (164 ± 37 pg/mL; n = 51) and following treatment (58 ± 16 pg/mL, p < 0.05; n = 51). Positive correlations between EBV DNA load and IL-10 (r(49) = 0.535, p < 0.01), between IL6 and IL-10 (r(49) = 0.474, p < 0.01) and between TGF and SCF (r(49) = 0.464, p < 0.01) were observed in patients following treatment. None of the parameters tested including IgA-VCA were associated with tumour stages. CONCLUSION: We conclude that among the parameters investigated, EBV DNA load and IL-6 levels were promising markers for the presence of NPC and for the assessment of treatment outcome

Validation of a new prognostic index score for disseminated nasopharyngeal carcinoma

Patients with metastatic nasopharyngeal carcinoma have variable survival outcomes. We previously designed a scoring system to better prognosticate these patients. Here, we report results on validation of this new prognostic index score in a separate cohort of patients. Clinical features and laboratory parameters were examined in 172 patients with univariate and multivariate analyses and a numerical score was derived for each independent prognostic variable. Significant independent prognostic variables and their scores assigned included poor performance status (score 5), haemoglobin <12 g dl−1 (score 4) and disease-free interval (DFI) (DFI⩽6 months (score 10) or metastases at initial diagnosis (score 1)). Maximum score was 19 and patients stratified into three prognostic groups: good, 0–3; intermediate, 4–8; poor, ⩾9. When applied to a separate cohort of 120 patients, 59 patients were good, 43 intermediate and 18 poor prognosis, with median survivals of 19.6 (95% CI 16.1, 23.1), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months, respectively. (logrank test: P=0.003). We have validated a new prognostic score with factors readily available in the clinics. This simple score will prove useful as a method to prognosticate and stratify patients as well as to promote consistent reporting among clinical trials