Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3 and STAT5, have been demonstrated in a variety of human tumours and cancer cell lines. However, data on the expression of these STATs in nasopharyngeal carcinoma (NPC) are limited. In this study, the expression patterns of STAT1, STAT3 and STAT5 were immunohistochemically examined on the archival specimens from 61 patients with NPC. Staining results of each STATs were then correlated with the clinical parameters and prognosis of these patients. The results showed that constitutive activation of STAT3 and STAT5 was detected in the majority, 70.5 and 62.3%, respectively, of the 61 tumour specimens. Furthermore, coexpression of activated STAT3 and STAT5 was found in 54.1% of the specimens. In contrast, constitutive activated STAT1 could only be detected in 8 (13.1%) cases. Surprisingly, following radiotherapy, patients with constitutive STAT5 activation, or activation of both STAT3 and STAT5, had better disease-free survival and overall survival than those without activated STAT5. To our knowledge, this is the first report providing the overall expression patterns and prognostic significance of specific STATs in NPC.
BACKGROUNDThe detection of tumor‐derived DNA within the circulation of patients with malignant disease using polymerase chain reaction (PCR)‐based strategies has opened a new avenue for the diagnosis and monitoring of these patients. Because of the universal association of Epstein–Barr virus (EBV) with the nonsquamous type of nasopharyngeal carcinoma (NPC; World Health Organization types II and III), the detection of cell free EBV DNA in sera from patients with NPC may be a valuable tool for monitoring the progress of tumors or to provide advanced warning of tumor recurrence.METHODSSerum samples were obtained from different patients, and cell free EBV DNA was detected with a conventional PCR approach. A total of 134 patients were sampled, including 36 patients with primary NPC, 28 control patients, 18 patients suffering from locoregional recurrence, 7 patients with distant metastasis, and 45 patients with NPC in clinical remission. A conventional PCR approach employing standard 35‐cycle and 50‐cycle reactions was used to detect cell free EBV genomes. Results from the two PCR cycles were compared to provide a semiquantitative picture of the relative quantity of EBV genome in each serum sample.RESULTSThe EBV DNA detection rates, i.e., the rates of positive detection, for 35‐cycle and 50‐cycle PCR analyses, respectively, were 38.9% and 75% for patients with primary NPC, 3.5% and 10.7% for control patients, 27.8% and 88.9% for patients with locoregional disease recurrence, 71.4% and 100% for patients with distant metastasis, and 7.1% and 36.5% for patients with disease in clinical remission. The rates of positive detection among patients with active disease all appeared to be significantly greater compared with the rates among patients with disease in clinical remission. Longitudinal data for six patients with recurrent tumors revealed a close correlation between the relative quantity of circulating cell free EBV genomes and the disease course of these patients. The sensitivity, specificity, positive predictive value, and negative predictive value of the 50‐cycle PCR analysis for detecting recurrent disease were 92%, 63.5%, 42.6%, and 96.4%, respectively.CONCLUSIONSThis study demonstrated that, by using a 50‐cycle PCR‐based approach, high sensitivity and high negative predictive value for detecting recurrent disease can be obtained from the detection of the cell free EBV genome in sera from patients with NPC. The 50‐cycle PCR analysis, therefore, may provide a simple, clinically useful adjuvant method for monitoring patients with NPC. Cancer 2002;94:723–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10251
Mcl-1 protein is a new member of the bcl-2 protein family. It is believed to be a blocker of apoptosis but might be different from bcl-2 in the control of apoptosis. Using immunostaining of formalin-fixed, paraffin-embedded sections, we investigated the expression of Mcl-1 in 42 thymic epithelial tumours: three medullary thymomas, five mixed thymomas, seven cortical thymomas, eight well-differentiated thymic carcinomas, 14 squamous cell carcinomas, four lymphoepithelioma-like carcinomas and one undifferentiated carcinoma, bcl-2 immunocytochemical localization was also performed for comparison. High-grade thymic carcinomas, especially squamous cell carcinomas, revealed more intense Mcl-1 immunoreactivity as compared to other subtypes (P < 0.001). In cases that co-expressed Mcl-1 and bcl-2, the less differentiated cells had more intense expression of bcl-2, while the more differentiated cells displayed stronger Mcl-1 immunoreactivity. The differential expression of Mcl-1 and bcl-2 in neoplastic cells provides evidence that these proteins may play different roles in the processes of programmed cell death in thymic neoplasms. The finding that thymic carcinomas have stronger immunoreactivity for Mcl-1 indicates that this protein could be a useful marker to differentiate aggressive thymic epithelial tumours from indolent ones.
The presence of human papillomavirus DNA in cholesteatoma may have some role in the development of middle ear cholesteatoma as well as in papilloma. In the present study, polymerase chain reaction and in situ hybridization with human papillomavirus (HPV)-6 and -11 DNA probes were used to detect the presence of HPV DNA in 32 human middle ear cholesteatomas. Only one specimen contained HPV-6 DNA. Although its occurrence may have been coincidental, it is also possible that the hyperproliferative epithelium of cholesteatomas might have some relationship with HPV infections.
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