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Background: Epstein-Barr virus (EBV) infection in nonsmall cell lung carcinoma (NSCLC) has been demonstrated in some ethnic groups. The pathobiology and the role of EBV and oncoprotein expression in these tumors have not been studied extensively. In this study, the authors investigated EBV-encoded RNA-1 (EBER1) transcripts by in situ hybridization and the expression of latent membrane protein-1 (LMP-1) and bcl-2 protein by immunohistochemistry in NSCLC patients from Taiwan, where nasopharyngeal carcinoma is endemic., Methods: A total of 127 cases of NSCLC (43 cases of squamous cell carcinoma [SCC], 67 cases of adenocarcinoma [AD], 12 cases of large cell carcinoma [LCC], and 5 cases of lymphoepithelioma-like carcinoma [LE]) were included. A sensitive polymerase chain reaction-derived, digoxigenin-labeled DNA probe for in situ detection of EBER1 transcripts was performed for the detection of EBV. Immunohistochemistry using the avidin-biotin-immunoperoxidase method was also performed to evaluate the expression of bcl-2 and LMP-1., Results: EBER1 was detected in 11 of the 127 NSCLC cases (8.7%; 6 SCC cases and 5 LE cases). All 5 LE cases were EBV-positive, whereas only 6 of the 43 SCC cases (14%), 0 of 67 AD cases, and 12 LCC cases were EBV-positive (P < 0.05). All five LE cases showed diffuse, strong, positive staining of tumor cells; five of the six SCC cases showed diffuse but weak staining. Among the nontumor epithelial cells, there was no EBER1 staining of any of the 11 EBER1-positive cases. The mean age of the LE patients was 10 years younger than that of the patients with other histological types. All 5 LE patients were nonsmokers, whereas 3 of the 6 patients with EBER1-positive SCC (50%) were smokers. EBER1 expression did not correlate with the 2-year survival rate of overall cases, but all 5 LE patients were alive without clinical evidence of disease at last follow-up. Gender, lymph node or distant metastasis, and clinical stage were not found to have any correlation with EBER1 expression (P > 0.05). All LE cases had bcl-2 oncoprotein expression (100%). This frequency was significantly different from other histologic types (P < 0.05). The LMP-1 detection rate was low and demonstrated no correlation with bcl-2 expression., Conclusions: In this study, the authors found that the primary LE of the lung is associated with young age, a history of not smoking, high bcl-2 immunoreactivity, and better survival rate. These characteristics demonstrate that EBV-associated LE of the lung is a unique entity. The findings of the current study suggest that EBV infection may play a different role in the tumorigenesis of primary LE of the lung than it does in other EBER1-positive NSCLCs.

Background: The clinical course of laryngeal squamous cell carcinoma (LSCC) varies considerably among patients. New biologic markers are needed to facilitate the stratification of individual patients within the conventional clinicopathologic stages of LSCC., Methods: Eighty-three LSCCs from an equal number of patients who received at least 10 years of follow-up were investigated for p53, p21WAF1/CIP1, and bcl-2 protein expression by immunohistochemical techniques. The results were correlated with various clinicopathologic parameters, DNA content, and patient outcome by univariate and multivariate statistical analyses., Results: Stage IV disease, large tumor size (>3 cm), positive lymph node status, extranodal extension, and p53 overexpression (in > 75% of cells) correlated significantly with prognosis in univariate analysis. There was no correlation between patient outcome and age, gender, race, histologic differentiation, or expression of bcl-2 or p21WAF1/CIP1. In multivariate analysis, lymph node status and p53 overexpression were the only factors significantly associated with survival., Conclusions: High p53 expression and positive lymph node status were independent predictors of the outcomes of patients with LSCC. These factors may assist in prognostication and better classification of patients for treatment.

Background: Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). Detection of EBV in biopsy specimens may serve as a tumor marker., Methods: To assess the sensitivity and specificity of the polymerase chain reaction (PCR) and in situ hybridization in the diagnosis of NPC, formalin fixed, paraffin embedded nasopharyngeal biopsies from patients in Taiwan suspected of having NPC were studied., Results: In specimens from 107 patients with NPC, EBV was detected by PCR in 97 cases (90.7%) and by EBER in situ hybridization in 105 cases (98.1%). In specimens from 61 patients without neoplasia, EBV was detected by PCR in 7 cases (11.5%) and by EBER in situ hybridization in 0 cases., Conclusions: These results suggest that although EBV DNA may occasionally be detected in nonneoplastic nasopharyngeal tissues, cells expressing EBER are not. EBER in situ hybridization may therefore prove to be a useful adjunct in the diagnosis of NPC.

Background: The association of Epstein-Barr virus (EBV) with nasopharyngeal carcinoma (NPC) is well documented. Previous studies reported abundant expression of EBER1 in primary NPC and tumors metastatic to lymph nodes. However, a large series of case studies correlating World Health Organization (WHO) histologic subtypes with EBER1 is needed., Methods: The authors applied the EBER1 in situ hybridization to investigate the expression of EBER1 in 140 primary NPCs, 11 metastatic tumors to lymph nodes, 6 metastatic tumors to bone marrow, and 2 metastatic tumors to the liver. All 19 metastatic tumors had paired specimens from their primary NPCs for comparison. The in situ hybridization method was performed on paraffin embedded tissues by using polymerase chain reaction-derived, digoxigenin-labelled EBER1 DNA probes., Results: The EBER1 signal was identified in nuclei of malignant epithelial cells in 135 of 140 (96.4%) primary NPCs, including 4 of 5 (80%) WHO-I histologic subtypes, 71 of 73 (97.3%) WHO-II histologic subtypes, and 60 of 62 (96.8%) WHO-III histologic subtypes (P > 0.05). However, the positive hybridization signal in WHO-I NPC was less in proportion to malignant cells, usually limited to basal cells, than in other histologic types of NPC. In 10 of 11 specimens with metastases to the lymph nodes, hybridization was always limited to the malignant cells and not associated with lymphocytes. All 10 paired primary NPCs also demonstrated positive EBER1 hybridization. Only one paired specimen showed negative EBER1 in primary NPC and a metastases to a lymph node. Eight distant metastases, all EBER1-positive in their primary NPC, also demonstrated positive EBER1 hybridization signals in the malignant cells. The proportion of EBER1 positivity in metastatic NPC is higher than that in primary lesions as observed in paired specimens from the same patient., Conclusions: Because of abundant expression of EBER1 in primary NPC as well as in metastatic malignant cells, it is recommended that EBER1 in situ hybridization be performed on routinely processed specimens whenever NPC is suspected.