J.D. Langdon

Secondary alveolar bone grafting in clefts of the lip and palate

A short review of the literature is presented outlining the role of alveolar bone grafting in cleft patients. An analysis of a series of 47 secondary alveolar bone grafts in 34 patients is presented. The age range was 7-24 years. At the time of evaluation, 30 canines were in final occlusion and good alveolar bone levels were present in 83% of patients. Of the 13 bilateral cases (26 clefts), 14 canines were in final occlusion and all cases had good alveolar bone levels. No major complications were encountered. The graft was completely resorbed in 3 cases (6.4%) only.

Oral cancer: the behaviour and response to treatment of 194 cases.

During the 16 year period 1960-1975, 350 cases of Oral Cancer were seen in the Department of Oral and Maxillo-Facial Surgery at the London Hospital. Detailed records were available for 250 patients. After excluding tumours of the salivary glands, sarcomata and tumours of the reticulo-endothelial system 194 cases remained and these were subjected to a computer analysis. The overall 5 year survival figure, not corrected for age and sex was, 32.8%. The local recurrence rate for all sites was 44%, 90% of these recurred within 2 years of diagnosis. The overall uncorrected 5 year survival figure for females was 42.1% and that for males was 22.9%. Analysis of the material has not provided a satisfactory explanation for this; lesions do not present at an earlier stage in females neither do they occur in younger patients. The distribution of the lesions by site and histology was the same for both sexes. Survival rates analysed by clinical staging at presentation confirm that the prognosis for early stage lesions is very much better than for late stage lesions, the 5 year survival for Stage I being 50% whereas that for Stage IV is only 20%.

Expression of epidermal growth factor receptor on oral squamous cell carcinoma.

The expression of the receptor for epidermal growth factor (EGF) in normal oral mucosa, papillomas and squamous cell carcinoma (SCC) has been determined by immunohistology and autophophorylation studies. Immunoreactive receptor was localised using two antibodies which recognise the receptor; EGFR1 which reacts with sequences in the external domain of the receptor and F4 which recognises sequences in the internal domain. EGFR was present on basal, suprabasal and some spinous cells of normal oral mucosa. Regional variation in the distribution of receptor was apparent. A similar pattern of receptor expression was seen on oral papillomas. The distribution and intensity of epidermal growth factor receptor (EGFR) expression varied between 20 patients with oral SCC. The staining patterns seen with the two antibodies were similar on all tissue types. The protein tyrosine-kinase activity of the receptor present on eight oral SCC was also examined by immunoprecipitation and autophosphorylation studies. This procedure also demonstrated variations in the amount of functional EGFR in these tumours. There was no significant correlation between the level of EGFR expression and tumour behaviour.

Expression of the tumour suppressor gene p53 in oral cancer

In this preliminary series, the product of the tumour suppressor gene p53 was detected in 12/15 cases of oral squamous cell carcinoma (SCC) and in two cases of leukoplakia. The tumours either expressed the mutant form of p53 throughout the specimen or contained focal areas of positive cells. p53 expression was commonly observed in tumours obtained from patients who were heavy smokers and drinkers suggesting that alterations in the p53 gene may be one of the sites of genetic damage in this group of patients.

The role of angiogenesis in the spread of oral squamous cell carcinoma

Microvessels were counted in 41 primary oral squamous cell carcinomas using JC70 antibody to PECAM (CD31). The counts were compared with clinical and pathological indicators of tumour behaviour including lymph node status, tumour stage, type of histological differentiation, size and velocity of tumour growth. Tumour microvessel counts correlated with lymph node metastasis (p < 0.001). This association was independent of tumour size, velocity and type of histological differentiation and when all the variables were analysed by multivariate analysis only vascular count showed a significant association with lymph node metastasis.

Location of candidate tumour suppressor gene loci at chromosomes 3p, 8p and 9p for oral squamous cell carcinomas.

To help define the location of tumour suppressor genes implicated in the pathogenesis of oral squamous cell carcinoma (SCC), we have used microsatellite assay and restriction fragment length polymorphism (RFLP) analysis to screen 48 primary SCC for allelic imbalance (AI) with 32 polymorphic markers at chromosome 3p, and prepared a detailed deletion map. The finding of a high frequency of AI at specific regions, together with the presence of multiple small interstitial deletions involving these loci, identifies 5 areas at this chromosome arm that may harbour tumour suppressor genes. No sequence aberrations affecting the von Hippel Lindau (VHL) and fragile histidine triad (FHIT) genes, which reside within the candidate tumour suppressor gene areas at this chromosome arm, were identified. A more limited analysis of polymorphic sequences at 8p and 9p supports the existence of at least 2 areas that harbour tumour suppressor genes at 8p and evidence that additional targets for deletion reside centromeric and telomeric to the p16 gene at 9p21. Int. J. Cancer 83:318–325, 1999.

Combined treatment of adenoid cystic carcinoma of the salivary glands

A retrospective review of the experience of a single surgeon over a 20-year period is presented. Fifteen patients with primary adenoid cystic carcinoma of the major (6) or minor (9) salivary glands underwent combined treatment with wide local excision and radical postoperative radiotherapy. The actuarial survival is 100% at 5 years and 62% at 10 and 15 years. The disease-specific survival is 100% at 5 years and 86% at 10 and 15 years. There were no loco-regional recurrences. Wide local excision and radical postoperative radiotherapy seems to be an effective treatment for adenoid cystic carcinoma of the salivary glands.

Tumours of the head and neck in children. A clinico-pathological analysis of 1,007 cases.

Tumours of the head and neck in children are uncommon, representing only 2-3% of all head and neck tumours. During the twenty year period 1964-1983, 12,876 childhood tumours were submitted for pathological diagnosis. Of these 1,007 (7.8%) were in the head and neck region, and it is this group that has been analysed. 30.6% (308 cases) were malignant neoplasms, 27.8% (280 cases) were benign neoplasms, 24.2% (244 cases) presented as tumour-like conditions and 17.4 (175 cases) were dysplasias arising from embryonal remnants. The overall sex ratio was 1.5:1 in favour of males. Lymphomas accounted for 15.9% overall (52.3% of the malignant neoplasms). Of benign tumours, haemangiomas were the most frequent (38.5%) and of the tumour-like conditions, dermoid and epidermoid cysts accounted for 36.1%. Of the embryonal remnant dysplasias, thyroglossal duct cysts accounted for 71.4%.

Complications of parotid gland surgery

In a consecutive series of 61 parotid operations only one case of unexpected permanent facial nerve injury was seen although transient disturbances of facial nerve function were more common. Freys syndrome subsequently developed in 13% of patients although its onset was delayed on average for 22.2 months.

New insights into p53 protein stabilisation in oral squamous cell carcinoma

p53 is a transcription factor which regulates cell proliferation and apoptosis to prevent division of potentially malignant cells. In many tumours mutation of the p53 gene leads to stabilisation of this protein which can be detected by immunohistochemistry (IHC). However, there are many reports describing detection of p53 by IHC in the absence of gene mutation, and in these cases other factors stabilise p53. To shed light on the mechanisms which permit detection of this protein in these mutation-negative cases we have examined 45 primary oral squamous cell carcinomas (SCCs) by IHC and gene sequencing for p53 (exons 4-8) and related the results to a FAL score (determined using microsatellite assay and expressing the number of loci showing allelic imbalance as a fraction of the total number of informative markers for each case). We also investigated the pattern of MDM2 expression in these tumours. High levels of p53 protein were detected in 24/45 cases and point mutations involving exons 4-9 were seen in 11 cases. A further four cases harboured deletions or a stop codon. For 6/48 cases there was concordance of AI within the p53 gene and mutation. However nine cases showed p53 mutation only and 5 AI without mutation, suggesting that oral tumours frequently retain one normal p53 allele. Detection of p53 by IHC correlated strongly with the FAL score. Thus whilst it is possible that some tumours harbour p53 mutations outside the open reading frames examined, or are missed due to sequencing a mixture of normal and tumour tissue, a subgroup of tumours may express high levels of wild-type p53 as a reflection of the high FAL score and ongoing genomic stress. Levels of MDM2 transcripts and protein were similar in all SCCs examined. However, MDM2 may be non-functional, or there may be defects affecting other important regulatory proteins in tumours which which express wild type p53 protein.