Mutation and methylation analysis of TP53 in adrenal carcinogenesis.

AIM: To investigate the role of coding region mutation and promoter hypermethylation of TP53 in adrenocortical cancer formation. METHODS: Twenty sporadic adrenocortical cancers (ACCs) and five normal adrenal tissue samples were available for analysis. Coding region mutation of TP53 in 20 ACCs was examined by polymerase chain amplification using intronic primers for exons 2-11 and direct sequencing of the product. In 10 ACCs and five normal adrenal tissue specimens, methylation of the 16 CpG sites within the TP53 promoter was examined using bisulphite methylation sequencing. RESULTS: Coding region mutation in TP53 was demonstrated in 5 of 20 ACCs. There were four mis-sense mutations and one frameshift mutation. Four of 5 patients with a TP53 mutation had metastases at diagnosis or detected soon thereafter and 3 of 4 died of disease within 12 months of surgical resection. No methylation was seen in the TP53 promoter in 10 ACC and the five normal adrenal tissues examined. CONCLUSION: Coding region mutation in TP53 occurs in 25% of ACCs with a trend toward a poorer prognosis. Promoter methylation of TP53 is not present in ACC as a mechanism for tumour suppressor gene (TSG) inactivation and, therefore, other genes in the 17p13 region are implicated in adrenal carcinogenesis.

Seroma formation after axillary lymphadenectomy with and without the use of drains.

Seroma formation after axillary lymphadenectomy is common. We performed a randomised controlled trial comparing seroma rate and volume after axillary lymphadenectomy with and without use of drains. In this study, there was no difference in incidence of seroma formation between patients who did and did not have a drain inserted after axillary lymphadenectomy for breast cancer. Undrained patients, however, had larger volume seromas of longer duration which required more aspirations. There was a tendency for undrained patients to have fewer complications when compared to patients with drains.

Echogenicity of breast cancer: is it of prognostic value?

Echogenicity of colorectal metastases to the liver has been shown to correlate with prognosis. While there have been many studies looking at the echogenicity of breast cancer, there has been no study relating the issue of echogenicity to prognosis of breast cancer. In this study, we found that hyperechoic and mixed echogenicity breast cancers are rare compared to hypoechoic breast cancers. There was, however, no difference in the groups with respect to histological size, grade, axillary metastases, hormone receptor status and lymphovascular invasion.

Histamine in human breast cancer.

BACKGROUND: Histamine inhibits lymphocyte function in vitro at concentrations of greater than 10(-6) mol/l. The aim of this study was to determine whether histamine concentrations in breast cancers were sufficient to produce an immunological effect. METHODS: Tumour and adjacent normal breast content of histamine was measured using a radioenzymatic assay in 29 patients having surgery for breast cancer. RESULTS: The median content of histamine in breast cancer tissue was 5.4 (range 0.9-27.3) microg/g (median concentration 4.5 x 10(-5) mol/l), and was significantly greater than that in adjacent breast tissue (P = 0.007). CONCLUSION: The concentration of histamine in breast cancer was sufficient to inhibit lymphocyte function and could be locally immunosuppressive.

Aspects of the psychological management of breast cancer.

Psychological factors influence the survival of patients with breast cancer through the early detection of the cancer and through compliance with the treatment. There is now evidence that psychological factors also influence the immune factors which control micrometastases. In particular, stoical acceptance of cancer is associated with a shorter survival of the patient, while the expression of hostility towards the cancer is associated with a longer survival of the patient. Unrecognized psychological morbidity can impair the quality of a patient's life for years. Such psychological morbidity may be reduced by more open communication with the patient, by encouragement of the expression of feelings (especially anger), by preoperative diagnosis of the cancer by biopsy and by a greater time allowance before a mastectomy is performed. Morbidity may also be reduced by the encouragement of patients to take an active part in their treatment decisions, by the avoidance of a mastectomy, by immediate breast-reconstruction surgery, and by appropriate psychological support which includes self-help techniques, such as meditation. Breast cancer can be a positive turning-point in a person's life.

Ego defences and affects in women with breast symptoms: a preliminary measurement paradigm.

Terms derived from psychoanalytic theory such as the concepts of ego defences and affects, have often been regarded as inaccessible to operational analysis and measurement and therefore devoid of empirical meaning. However, these explanatory terms are frequently employed in hypotheses concerning the determinants of behaviour and outcome in naturally occurring illnesses, such as breast cancer as well as other life crises and stress situations. The results of the present study demonstrate not only that it is possible to operationally define and measure the ego defences and affects associated with the crisis induced by finding a breast symptom suggesting cancer and awaiting biopsy, but also that on the basis of such measurement, behaviour related to breast cancer can be predicted and hypotheses concerning the relevance of these variables to aetiology put to the test. The operational definitions and measurement methods described could also be modified for application in other crisis situations to which ego defences and affects are thought to be pertinent and the results of these operations compared empirically to determine the extent of their convergence. the methods can be used by independent observers with different theoretical and professional backgrounds. The delay by women in reporting breast symptoms to their doctors was strongly related to a combination of non-rational, unconscious psychological factors. Those who delayed used the ego defences of denial and suppression, not intellectualization-isolation, and verbally expressed depression but not anxiety while showing behavioural manifestations of anxiety. Conscious factors such as fear and education were unrelated to the length of delay. These findings have important implications for educators and doctors concerned with the early detection of breast cancer.

The doctor and the patient in early breast cancer diagnosis.

Breast cancer mortality has not fallen in 30 years, and a renewed attempt at early diagnosis should be made. A study of women's attitudes to breast cancer and surgery has shown their behaviour to be influenced mainly by unconscious factors, including ego-defences, anxiety and depression. Doctors know that early breast cancer treatment is desirable, but the proportion of women having their breasts examined, or being taught breast self-examination, is small. Further attempts at reducing delay in breast cancer treatment must take into account the unconscious processes affecting behaviour, and individual doctors could play a greater part by the education of women in their surgeries.

Detection and diagnosis of early breast cancer.

Breast cancer mortality can be reduced by early detection and treatment, but the cost of diagnosis of early tumours from amongst the larger number of non-malignant disorders found as a result of public education and population screening is likely to be prohibitive, both economically and emotionally, as long as admission to hospital for biopsy and possible immediate mastectomy remains the major diagnostic policy. An alternative policy is proposed for the management of women with breast symptoms, which avoids operation on most patients without cancer and detects the smallest tumours, by means of mammography, fine-needle aspiration biopsy, large-needle biopsy and outpatient open biopsy. Such a policy is likely to provide positive reassurance with the least emotional distress for that majority of women with breast symptoms who do not have malignant disease, and this is likely to lead to more positive behaviour in the community such as regular breast self-examination and the early reporting of breast symptoms. Only women with malignant disease need be admitted to hospital for major breast surgery, thorough preoperative investigation could be confined to this group, and they could receive positive counselling to reduce their emotional stress. Such a policy is likely to be economical of health resources so that all women with breast symptoms and other risk factors could be encouraged to undergo annual examination, and any suspicious findings could be adequately investigated. In this way many more cancers could be detected while still small and curable, and a fall in breast cancer mortality in the community might be expected.

The outpatient diagnosis of breast lumps.

A plan of management, based on a personal experience of 421 cases, has been developed for the outpatient diagnosis of breast symptoms. In the majority of patients the presence of absence of malignancy can be established with a high degree of certainty before biopsy, and benign masses can be safely excised on an outpatient basis. Only those patients whose breast symptoms and findings suggest malignancy need be admitted to hospital and prepared for major breast surgery. This plan has been shown to be safe, while avoiding unnecessary hospital bed occupancy.

Breast loss and delay in breast cancer diagnosis: behavioural science in surgical research.

By the use of the methods of behavioural science, a study of women's attitudes to breast cancer and to breast surgery was carried out to provide firm data which might begin to settle the argement regarding conservative surgery for breast cancer. Conscious fears, including that of mastectomy, were found to have no significatn influence on the time that a woman takes to report the presence of a breast lump to her doctor, or to commence the practice breast self-examination. The length of delay is determined by unconscious, non-rational processes, and other factors beyond her control. Rational argument, therefdore, such as that earlier diagnosis will permit more conservative surgery including partial mastectomy, will not influence women to present any earlier or to practise breast self-examination.

Organization of clinical trial on national scale: management of early cancer of the breast.

From a study of the organization of a national clinical trial on the management of early cancer of the breast in women there appear to be overwhelming advantages in studying large numbers of patients. To this end centres abroad have been encouraged to join. All the evidence at present suggests that it is feasible to organize a study on this scale, that the documentation and follow-up are accurate, and that the enthusiasm of the participants can be successfully fostered and maintained.