European journal of cancer. Part B, Oral oncology最新文献

To study the use of p53 as a diagnostic tool in head and neck squamous cell carcinoma (HNSCC), we analysed 15 primary tumours (PT) and matched lymph node metastases (LNM) for overexpression and mutations of p53. The primary goal was to study whether differentiation between primary and metastatic disease through their p53 status would be possible. Immunohistochemistry for p53 protein (antibody BP 53-12-1) was performed. Mutations of the p53 gene were detected by exonspecific amplification of DNA (exons 4–9), followed by exon analysis using denaturing gradient gel electrophoresis (DGGE). Mutant exons were sequenced. p53 overexpression was detected in seven (47%) of the PT and in seven (47%) of the LNM. 6 patients (40%) exhibited p53 protein overexpression in both PT and LNM. 2 patients had a different p53 protein expression in each sample. Mutations in the p53 gene were detected in 6 patients (40%) in the PT and in 7 patients (47%) in the LNM. In 2 patients (13%), the same mutation was found in the PT and in the LNM. 9 patients (60%) had a different mutation in each sample. We conclude that a poor correlation exists between p53 protein overexpression and p53 gene mutation in HNSCC. Also, a poor correlation for both detection techniques exists, when PT and LNM are compared. The p53 status may seem to differ between PT and LNM because of polyclonality in the PT. More sensitive detection techniques could be promising.

The bcl-2 oncogene is a member of a family of genes encoding for proteins which regulate apoptosis (programmed cell death). Recent evidence suggests that the bcl-2 protein is regulated by a homologous protein bax which counteracts its effects and promotes apoptosis. Overexpression of bcl-2 has been reported in a number of human cancers, although correlations with tumour differentiation and clinical outcome are conflicting and depend on tumour type and site. We studied bcl-2 and bax protein expression in adjacent serial sections of 30 squamous cell carcinomas of the oral cavity and correlated this with tumour differentiation. Examination of normal epithelium showed bcl-2 expression confined to basal keratinocytes and dendritic cells. The bax immunostaining was seen throughout the thickness of the epithelium but was most intense in the suprabasal cells. Overall, moderate or marked immunostaining for bcl-2 was identified in $\text{18}\text{30}$ (60%) carcinomas and for bax in $\text{19}\text{30}$ (63%) tumours. The bcl-2 immunoreactivity was strongest in the poorly differentiated carcinomas where $\text{6}\text{7}$ (86%) showed strong staining. By contrast, bax immunoreactivity was strongest in the well-differentiated carcinomas with $\text{8}\text{11}$ (72%) staining strongly. In the well-differentiated tumour islands, there was inverse topographic distribution of bcl-2 and bax, with both proteins showing a pattern that recapitulated normal epithelium. Upregulation of bcl-2 protein was identified in dysplastic epithelium adjacent to invasive tumour and in many cases there was reduced bax immunostaining. These results suggest that alterations of bcl-2 and bax may play a role in the development of squamous cell carcinoma. Furthermore, disturbances of protein expression in dysplastic epithelium suggest a role in the early stages of epithelial carcinogenesis.

39 patients with marginal zone B cell lymphoma (MZBCL) of the parotid glands (stages I or II) were studied. They were randomized to be treated with either radiotherapy alone (extended fields, 4500 cGy) or radiotherapy (the same schedule) plus adjuvant chemotherapy (cyclophosphamide, vincristine and prednisone). The end points were survival and time to treatment failure (TTF). Patients who received radiotherapy alone had a complete remission rate of 100%, the TTF was 90% at 5 years and overall survival at 5 years was 90% with no statistical difference when compared with patients who received combined therapy [100, 80 and 95%, respectively (P= 0.5)]. Although adjuvant chemotherapy was well tolerated, the use of this therapeutic approach in patients with early stage MZBCL did not offer any advantage over radiotherapy alone as the initial treatment. Until now, radiotherapy was considered the treatment of choice in this clinical setting of patients.

Acute oral complications are serious and disabling secondary effects for patients undergoing cancer therapy. Therefore, the authors wanted to develop a sensitive and specific method to measure oral mucosal changes associated with autologous bone marrow transplantation. 14 patients, all volunteers, 18–56 years old, receiving conditioning regimens of cyclophosphamide and total body irradiation were included. The clinical changes of the oral mucosa and functional modifications were scored daily, over 21 days with a 16 item scale, ranging from 0 to 3. A daily index of mucositis (DIM) was established by adding the scores obtained for the 16 items and a cumulative score of oral mucositis was obtained by the addition of the 21 DIM for assessing the severity of oral mucositis throughout its duration. The internal consistency measures (Chronbach alpha) were strong (range 0.80–0.97). A scale of equivalence, pre-established in comparison with pre-existing general mucositis rating scales, permitted a day by day simple classification in a 4-grade scale, to be obtained. Support for the validity of the suggested scale is presented. This scale may help to improve the study of oral complications of cancer therapy.

CYFRA 21-1 is a fragment of cytokeratin expressed by simple epithelia and their malignant counter-parts. Serum CYFRA 21-1 levels were studied in 240 new cases of nasopharyngeal carcinoma and 19 patients who developed distant metastases. A reference range of <2 U/ml for our local Chinese population was established in 55 sex- and age-matched healthy volunteers. The nasopharyngeal carcinoma patients had significantly higher marker levels than the healthy controls and the mean level increased with advancing stage. However, the low percentage of elevation in early stages means that the marker is not useful for screening. The overall percentage (52.5) of elevation in 240 newly diagnosed squamous cell carcinoma of the nasopharynx is comparable to that of squamous cell carcinoma of the lungs, suggesting that the expression of CYFRA 21-1 is related to the cell type rather than the tissue type of the carcinoma. 46 (95.8%) of 48 patients with metastatic nasopharyngeal carcinoma showed an elevated value of CYFRA 21-1. This extremely high percentage implies that it is very unlikely for a patient with a normal value to have distant metastasis. This may permit major economies in radiological screening for distant metastasis. Preliminary results from serial measurement of the marker indicated its potential for monitoring response to treatment and for early detection of distant metastasis.

Advanced cancers of the oral cavity continue to be a therapeutic challenge. Despite significant improvements in radiotherapeutic techniques and adjuvant chemotherapy, patients usually die after a short period. Recent progress in reconstructive techniques has made major glossectomy (subtotal, near total, total or extended total) a reasonable palliative and potentially curative approach. It is the purpose of this study to report a series of 106 patients treated from 1985 to 1994 regarding surgical complications and prognosis. All but 1 patient undergoing major glossectomy had squamous cell carcinoma. Primary tumour sites were oral tongue (50 cases), base of the tongue (18 cases), floor of the mouth (28 cases) and other parts of the mouth (10 cases). Tumour stages were: 25 T3, 57 T4, 24 Tx, 34 N0, 20 N1, 32 N2a-N3, 20 nx. The types of glossectomy were as follows: 24 subtotal, 31 near total and 51 total. A total laryngectomy was performed in only 6 cases. A neck dissection was performed in all but 3 patients: 12 unilateral radical neck dissection (RND), 1 unilateral supra, omohyoid (SOH), 39 simultaneous bilateral RND, 8 simultaneous bilateral SOH, and 43 RND associated to contralateral SOH. A pectoralis major myocutaneous flap was used to repair the operative defect in 96 cases. Complications were seen in 52 cases (49%). The most common complications were wound infection (17 cases), flap necrosis (15 cases) and fistula (15 cases). Significant transient aspiration was seen in 8 patients. At the study closing date, 30 patients were alive without disease, 5 had recurrent disease, 47 died of cancer, 14 died of causes not related to cancer or treatment and 10 were lost to follow-up. The 5-year actuarial survival rates were, respectively, 45%, 18% and 18% for T3, T4 and Tx. Other significant variables were pN stage (P= 0.0672) and year of admission (0.0318). In conclusion a major glossectomy without laryngectomy whenever possible is a safe procedure for a selected group of patients with advanced tongue and floor of the mouth cancer. The actuarial survival rates presented suggests that, in a very select group of patients, major glossectomy is a surgical procedure to be considered.

Chemoprevention with retinoids is currently an experimental approach to prevent local relapses and second primaries in treated head and neck cancer patients. We evaluated the effectiveness of vitamin A in preventing the above events in a randomised trial involving 106 head and neck cancer patients who had achieved complete regression of their disease with radiotherapy and/or surgery. They were randomised to receive retinyl palmitate (200,000 IU per week for 1 year) or placebo. 50 subjects on vitamin A and 43 on placebo completed 1 year supplementation; 49 in the former group and 42 in the latter could be evaluated over a 3 year period from the initiation of the study. One fifth ($\text{11}\text{56}$) of patients in the vitamin A group and one tenth ($\text{5}\text{50}$) in the placebo group had loco-regional recurrence. The frequency of recurrences in stage I patients in the vitamin A group was higher compared to the placebo group, although it was not statistically significant. No second primaries were observed in the vitamin A group; 2 patients in the placebo group had second primaries. No clinically obvious side effects were observed with vitamin A. The higher frequency of recurrences in the vitamin A group is of concern although it may be a chance finding given the small size of the trial. The effect on second primaries is consistent with other observations reported in literature.