Increased risk of non-small cell lung cancer and frequency of somatic TP53 gene mutations in Pro72 carriers of TP53 Arg72Pro polymorphism

The aim of this study was to assess whether the TP53 Arg72Pro polymorphism is associated with an increased risk of non-small cell lung cancer (NSCLC). Additionally, in NSCLC patients, we investigated a potential association between this polymorphism and somatic TP53 gene mutations in tumour cells. The study group included 240 NSCLC patients who underwent curative pulmonary resection. The control group (576 healthy subjects) was matched for sex and cigarette smoking. TP53 Arg72Pro polymorphism was determined by denaturing high-performance liquid chromatography. Tumours from 157 NSCLC patients were analysed for mutation in TP53 exons 5-8 by single strand conformation polymorphism, followed by sequencing of samples with different band pattern. Tumours from the remaining 83 patients were subjected to a direct sequencing of TP53 exons 5-8. The proportion of Pro homo/heterozygotes versus Arg homozygotes was significantly higher in NSCLC patients (54%) than in controls (46%, p = 0.034). The crude odds ratio for NSCLC development in Pro72 allele carriers was 1.39 (95% CI: 1.03-1.88). When adjusted for sex, age and smoking status in the multivariate logistic regression model, odds ratio for NSCLC development was 1.28 (95% CI: 0.91-1.80). Somatic TP53 mutations were found in 62 out of 240 NSCLC patients (26%), more frequently in Pro carriers (31%) than in Arg homozygotes (20%, p = 0.06). These results indicate that the TP53 codon 72 Pro allele may increase the risk of NSCLC. Additionally, the correlation between Pro72 and somatic TP53 mutations suggests that Pro72 allele carriers may be predisposed to tumour development along a p53 associated form of NSCLC, a finding that warrants further investigations.     

<Emphasis Type="Italic">HER2</Emphasis> Amplification Has no Prognostic Value in Sporadic and Hereditary Ovarian Tumours

Whereas HER2 amplification is a well-known phenomenon in breast tumours, its frequency and clinical importance in ovarian cancer have not been established. The aim of the study was to compare the frequency of HER2 amplification in hereditary (BRCA-positive) and sporadic (BRCA-negative) ovarian tumours and to estimate the association of this gene alteration on clinical outcome in ovarian cancer patients. We analysed HER2 amplification in 53 ovarian tumours: 20 from mutation carriers (18 in BRCA1 and 2 in BRCA2 gene) and 33 from non-carriers. Fluorescence in situ hybridization for HER2 was performed on 'touch' slides from frozen tumour samples or formalin-fixed, paraffin-embedded tissue. Our results indicate that high amplification (HER2: centromere ratio>5) is an infrequent phenomenon in ovarian tumours (6/53 cases). It occurs in both hereditary (4/20) and sporadic (2/33) tumours and no difference in the frequency of HER2 amplification exists between these groups. There is no significant difference in the clinical outcome of patients with HER2 amplified and non-amplified tumours (p = 0.3). Our results suggest a different biological role of HER2 amplification in ovarian and breast cancer.     

Two mosaic cases with nonfluorescent Y chromosome analysed with Y-specific DNA probes

Two cases of a nonfluorescent Y (Ynf) chromosome were diagnosed: one in a male, the other in a female. Both had similar complex mosaic chromosome constitutions with a 45,X cell line. DNA studies were applied in both cases for verification of the cytogenetic diagnosis. The results on the two patients were compared with data obtained from seven healthy men (46,XY), three healthy women (46,XX), two females with 46,XY karyotype, and from cell lines with 49,XXXXY and 48,XXXX chromosome constitution. The highly repetitive Y-specific DNA sequences located in the heterochromatic region of the long arm were absent in these patients. Differences in the composition of the euchromatic part of the Y chromosome were demonstrable in both patients. The highly repetitive Y-specific DNA sequences located in the heterochromatic region of the long arm were absent in these patients. Differences in the composition of the euchromatic part of the Y chromosome were demonstrable in both patients. The suggestion that the Ynf chromosome originates from a dicentric Y chromosome cannot be accepted as a complete explanation of the phenomenon, as it probably involves more complex molecular alterations of the abnormal Y chromosome. The presence of Ynf is associated with the presence of a 45,X cell line more often than in cases of simple Y chromosome deletions with the breakpoint localized in or below the Y euchromatin/heterochromatin junction.     

Root morphology of mandibular premolars in 40 patients with Turner syndrome

AIM: To analyse root morphology of mandibular premolars in 40 females with Turner syndrome. METHODOLOGY: All patients aged 18-50 years (mean+/-SD: 26.2+/-6.22) were clinically and cytogenetically diagnosed and divided into three groups according to karyotype: I-with 45,X (n=19); II-with 46,X,i(Xq) and other structural changes of this chromosome (n=8); III-with mos45,X/46,XX and other mosaic karyotype (n=13). The control group consisted of 30 healthy women aged 20-50 years (mean+/-SD: 31.52+/-5.21) who underwent dental treatment at the Department of Conservative Dentistry and Department of Periodontology and Oral Mucosa Diseases, Medical University of Gdańsk, Poland. The root morphology of mandibular premolars was studied based on orthopantomogram X-ray images. The results were analysed using chi-square test with Yates's adjustment. RESULTS: Separate mesial and distal root canals and separate root apices were noted on orthopantomograms in patients with Turner syndrome. Two-rooted mandibular first premolars were observed in 34% of cases in group 45,X (group I), in 31% of cases in the group with structural aberrations of chromosome X (group II) and in 31% of cases with mosaic karyotypes (group III). Two-rooted mandibular second premolars were observed in 39% cases in group 45,X and in 31% of cases in the group with structural aberrations of chromosome X and in 35% of cases with mosaic karyotypes. This type of root morphology was not observed in the control group. No significant difference was found between the three groups of Turner syndrome. CONCLUSION: Highly significant differences in root morphology of mandibular premolars between patients with Turner syndrome and a population control group were found.     

Postradiotherapy quality of life for head-and-neck cancer patients is independent of xerostomia

PURPOSE: To determine the relationship between quality of life (QOL) and xerostomia over time for patients undergoing radiotherapy (RT) for head-and-neck cancer in a prospective clinical trial. METHODS AND MATERIALS: Patients with head-and-neck cancer were randomized to pilocarpine (n = 65) vs. placebo (n = 65) during RT. QOL was measured using the McMaster Head and Neck Radiotherapy Questionnaire (HNRQ). Xerostomia was measured on a linear analog scale. No statistically significant differences were observed between arms; all 130 patients were analyzed together. RESULTS: Baseline QOL data were obtained for 98.5% of participants. The baseline HNRQ score of 5.7 declined significantly to 4.0 (p <0.0001) by RT Week 6 and returned to baseline (5.8) by 6 months after treatment. This represents a large, clinically important change of 1.7 of 7 (24%; effect size 1.34). The decline in HNRQ score during RT paralleled the onset of xerostomia on the linear analog scale (r = 0.36 at 1 month). After treatment, the QOL scores recovered without improvement in xerostomia. The trajectory of the linear analog scale score resembled that of the HNRQ's single xerostomia question (r = 0.75 at 1 month). CONCLUSION: Quality of life recovers to baseline after RT, despite persistent xerostomia. Either a response shift occurs or xerostomia in the absence of acute mucositis has a relatively small influence on overall QOL.     

Error in the delivery of radiation therapy: results of a quality assurance review

PURPOSE: To examine error rates in the delivery of radiation therapy (RT), technical factors associated with RT errors, and the influence of a quality improvement intervention on the RT error rate. METHODS AND MATERIALS: We undertook a review of all RT errors that occurred at the Princess Margaret Hospital (Toronto) from January 1, 1997, to December 31, 2002. Errors were identified according to incident report forms that were completed at the time the error occurred. Error rates were calculated per patient, per treated volume (>/=1 volume per patient), and per fraction delivered. The association between tumor site and error was analyzed. Logistic regression was used to examine the association between technical factors and the risk of error. RESULTS: Over the study interval, there were 555 errors among 28,136 patient treatments delivered (error rate per patient = 1.97%, 95% confidence interval [CI], 1.81-2.14%) and among 43,302 treated volumes (error rate per volume = 1.28%, 95% CI, 1.18-1.39%). The proportion of fractions with errors from July 1, 2000, to December 31, 2002, was 0.29% (95% CI, 0.27-0.32%). Patients with sarcoma or head-and-neck tumors experienced error rates significantly higher than average (5.54% and 4.58%, respectively); however, when the number of treated volumes was taken into account, the head-and-neck error rate was no longer higher than average (1.43%). The use of accessories was associated with an increased risk of error, and internal wedges were more likely to be associated with an error than external wedges (relative risk = 2.04; 95% CI, 1.11-3.77%). Eighty-seven errors (15.6%) were directly attributed to incorrect programming of the "record and verify" system. Changes to planning and treatment processes aimed at reducing errors within the head-and-neck site group produced a substantial reduction in the error rate. CONCLUSIONS: Errors in the delivery of RT are uncommon and usually of little clinical significance. Patient subgroups and technical factors associated with errors can be identified. The introduction of new technology can produce new ways for errors to occur, necessitating ongoing evaluation of RT errors for quality assurance. Modifications to processes of care can produce important reductions in error rates.