Allele loss from chromosome 17 in ovarian cancer.

In a number of human cancers genes capable of suppressing tumorigenicity have been identified and in some instances cloned. Successful isolation of such tumour suppressor genes has depended upon either the mapping of a locus which confers susceptibility to a specific tumour, or the finding of specific allele loss in the tumour cells of heterozygous individuals. In ovarian cancer it is known that a small proportion (approximately 5%) of tumours are due to inheritance (Lynch et al., 1989). However, as yet the locus responsible has not been mapped. The only incidence of allele loss in ovarian tumours reported is on the short arm of chromosome 11 using a c-Ha-ras I probe to detect an RFLP (Lee et al., 1989), and on 3p and 6 in a small number of cases (Ehlen & Dubeau (1990)). We describe here the results of analysis of 19 tumours for allele loss using a probe for a hypervariable locus on the long arm of chromosome 17. Approximately 77% (10/13) of tumours from informative patients showed complete or partial allele loss at this locus. Using a probe for the short arm of chromosome 17, 31% (4 of 13 informative patients) demonstrated allele loss at this position. These results suggest that possible involvement of more than one chromosomal locus in the development of ovarian cancer.

Homozygosity of the short arm of chromosome 17 in cervical carcinoma.

We have determined the frequency of heterozygosity of the short arm of chromosome 17 in 20 cervical tumours using the highly polymorphic probe pYNZ22. Only 25% of the tumours were heterozygous at this locus. This is significantly lower than the level of 86% heterozygosity for this locus in the general population indicating that loss of one allele occurs in cervical cancer. Heterozygosity for a locus on the long arm of the same chromosome showed no significant difference between the tumours and the general population indicating that genetic loss was confined to the short arm of the chromosome. The analysis of premalignant lesions showed 70% of patients were heterozygous suggesting that loss of material from the short arm of chromosome 17 took place at a late stage in tumour development. This report confirms predictions made from previous karyotypic analysis and is the first indication of allele loss on the short arm of chromosome 17 in cervical cancer.

Alcoholism in cancer of the head and neck.

One hundred patients with a diagnosis of head and neck cancer were investigated carefully for a history of alcoholism. A majority of cases had a severe drinking problem; in fact, alcoholism was twice as common as initially anticipated. Patients were frequently able to hide the problem from their physician. Often the true diagnosis was obtained only by closely questioning relatives and friends. Most patients with cancer of the tongue, tonsil and oro-pharynx were alcoholic. About one-half of the patients with supraglottic carcinoma were alcoholic. In the nasopharnx and true vocal cords, there was no association with heavy drinking. The study is of epidemiological interest but also has implications in the management of the malignancy, depending upon the anatomic site involved.

The incidence and pathogenesis of invasive cutaneous malignant melanoma in Northern Ireland.

Three hundred and four suspected cases of malignant melanoma diagnosed in Northern Ireland over a 5 year period have been reviewed. Two hundred and forty fulfilled the diagnostic criteria of invasive cutaneous malignant melanoma (CMM) and were accepted as suitable for analysis an incidence of 3.12. The female to male ratio for CMM in this study is 3:1. This excess of female lesions occurs at all major anatomical sites and for all tumour types. There are many thick melanomas in the province, and 67% of cases were greater than 1.7 mm thick. Each tumour type has a distinctive age curve. The implications of these findings are discussed. The evidence suggests that intrinsic factors are as important as extrinsic factors.

An analysis of the SCM test in cancer diagnosis.

A new diagnostic blood test for cancer, the Structuredness of Cytoplasmic Matrix (SCM) test, has been widely claimed to distinguish between normal healthy controls and patients with malignant disease. It has also been claimed that the test distinguishes between patients with nonmalignant conditions and patients with cancer. Furthermore, it has been stated that the test makes it possible to identify the specific type of tumor in each case. In view of the importance of these claims, the study was repeated under identical laboratory conditions. Six hundred and twenty-one blood samples from controls and various groups of patients were processed in an exhaustive investigation. Four objectives were set: (1) to apply the test to a group of normal healthy individuals; (2) to apply the test to a group of patients with nonmalignant disease; (3) to apply the test to a group of cancer patients; and (4) to attempt to relate the degree of positivity of the test, if any, to the extent or stage of the tumor. Using the results described, confirmation of any of the above claims was not achieved. From this study, it is concluded that the test is of no clinical value.

Poor prognosis for malignant melanoma in Northern Ireland: a multivariate analysis.

All cases of cutaneous malignant melanoma, CMM, diagnosed in Northern Ireland between 1974-1978 were reviewed, classified and followed up until the end of 1984. The overall 5 year survival is 54%, among the worst reported in recent literature. Multivariate analysis of these cases confirms some previous findings from other studies, but also reveals features not apparent in univariate analysis. Prognosis worsens with increasing thickness and the presence of ulceration. Likewise histopathological type has an independent effect on survival, ALM having the worst prognosis. Tumour profile emerges as a significant feature affecting prognosis, flat lesions having the poorest outlook, given their thickness. Survival is worse with increasing age. Anatomical site is less important than suggested by previous univariate analysis. Sex has little influence on prognosis when adjusted for the other variables. Cell type and pigmentation are of no prognostic value. Several features including diagnostic delay contribute to the poor overall survival for CMM in Northern Ireland. Educational intervention is essential if this trend is to be reversed.

Cutaneous malignant melanoma in Northern Ireland.

The results of two 5-year studies, for 1974-78 and 1984-88, of cutaneous malignant melanoma (CMM) in Northern Ireland show changes in the presentation of the disease. Although there is some evidence of earlier diagnosis, the rise in incidence has produced an overall increase in the number of cases with advanced disease.