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Biomedical subjects

U Chetty

Publications and source records attributed to U Chetty.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cutaneous malignant melanoma. Publicity, screening clinics and survival--the Edinburgh experience 1982-90.

The incidence of cutaneous malignant melanoma has increased considerably in south-east Scotland over recent years. In 1987 the Cancer Research Campaign launched a project to aid the early detection, diagnosis and treatment of malignant melanoma. Edinburgh, chosen as one of seven centres in the U.K. to participate in the study, was provided with funding for a direct access pigmented lesion clinic from 1987 to 1989. The changes in the pattern of cutaneous malignant melanoma before, during and after the publicity campaign have been examined; between 1982 and 1990. The incidence of malignant melanoma doubled from 5.7 to 11.4/100,000 per annum. The percentage of thin tumours (Breslow thickness < or = 1.5 mm) increased steadily and significantly (from 43% in 1982 to 68% in 1990), but the number of thick tumours (Breslow thickness > 3.0 mm) remained constant over the same period (22 +/- 3.8). The influence of publicity was assessed using a questionnaire. Those who were influenced by publicity were significantly younger and had more thin tumours (Breslow < or = 1.5 mm) than those who were uninfluenced by publicity. Five-year survival has significantly increased from 70% in the 1982-84 cohort to 84% in the 1987-89 cohort. The effect of the publicity campaign has been beneficial, but the impact on mortality cannot yet be assessed.

Female↗
PubMed1994

Ultrasonography as a method of measuring breast tumour size and monitoring response to primary systemic treatment.

Accurate measurement of change in tumour size is a prerequisite for the use of response-based regimens of primary systemic therapy for breast cancer. This study evaluated the accuracy of clinical assessment, mammography and ultrasonography in measuring tumour size and in monitoring response to treatment. Size was determined during the week preceding surgery and actual size measured from resected specimens. Sequential measurements were performed in 35 patients undergoing primary systemic treatment. There was moderate correlation between pathological and clinical size (n = 51, r2 = 0.68, P < 0.0001). Close correlation with pathological tumour size was observed for mammographic (n = 45, r2 = 0.84, P < 0.0001) and ultrasonographic (n = 52, r2 = 0.89, P < 0.0001) tumour size. Response was correctly evaluated by clinical assessment in 31 of 35 patients, by mammography in 20 of 35 and by ultrasonography in 31 of 35. Actual tumour size can be measured accurately by available imaging techniques but ultrasonography is the most practical and accurate method for monitoring response.

Adolescent↗
PubMed1994

Breast cancer incidence, penetrance and survival in probable carriers of BRCA1 gene mutation in families linked to BRCA1 on chromosome 17q12-21.

Eight breast cancer pedigrees with a high probability of containing individuals with the BRCA1 gene mutation (odds 79.2-99.9 per cent) were identified through genetic linkage analysis using probes located within q12-22 on the long arm of chromosome 17. Some 102 female relatives were successfully typed with one or both of adjacent markers D17S588 and D17S579, and 41 were probable non-BRCA1 mutation carriers. Of the remaining 61 women classified as probable BRCA1 carriers, breast cancer was diagnosed in 35. As expected from epidemiological segregation analysis studies, 13 of these had bilateral disease. Approximately two-thirds of women unaffected by malignancy and alive at the time of observation were non-BRCA1 carriers. Lifetime disease penetrance of the BRCA1 gene was 88 per cent and this plateau was reached earlier (by age 65 years) than that estimated in segregation analysis. The survival curve of patients with breast cancer was less steep in BRCA1 gene carriers than that in the general population; 5-, 10- and 20-year survival rates unadjusted for non-cancer deaths were 83, 63 and 41 per cent respectively. The 5-year survival rate was significantly higher in BRCA1 carriers than that in an age-matched Scottish population (P < 0.05).

Adult↗
PubMed1994

Colour Doppler studies of axillary node metastases in breast carcinoma.

Colour Doppler scans were carried out on 80 patients with breast carcinoma. Both the tumour and the lower axilla were scanned in all 80 patients. Seventy-five patients subsequently underwent axillary lymph node dissection and histological examination. The sensitivity of colour Doppler scanning for axillary node involvement was 70%, with a specificity of 98% and a positive predictive value of 96%.

Adult↗
PubMed1994

Critical determination of the frequency of c-erbB-2 amplification in breast cancer.

Tissues from 323 methacarn-fixed and paraffin-embedded breast cancers were assessed for c-erbB-2 gene amplification by differential polymerase chain reaction (dPCR). The sensitivity of dPCR was ascertained using cell lines with c-erbB-2 amplification, and the relationship between dPCR ratio value and gene copy number was established. In clinical material the technique was not affected by the DNA contribution of normal tissue elements or by cancer DNA ploidy change. c-erbB-2 gene amplification was detected in 55% of invasive cancers and in 66% of in situ cancers. c-erbB-2 protein overexpression in breast cancer cells, as determined by specific immunohistochemistry, was only detected in 11% of invasive cancers and 43% of in situ cancers. Comparisons show that a substantial number of cancers with c-erbB-2 amplification lack detectable protein overexpression. This illustrates the complex nature of c-erbB-2 gene disregulation in cancer and suggests that multiple combinations of biological events and consequences are possible.

Aged↗
PubMed1993

Genetic linkage analysis applied to unaffected women from families with breast cancer can discriminate high- from low-risk individuals.

Up to 20 per cent of cases of breast cancer diagnosed in women under the age of 45 years may be caused by an autosomal dominant gene. A present difficulty is differentiation of mutation carriers from non-mutation carriers in high-risk families. Genetic linkage analysis has been used to localize a susceptibility gene (BRCA1) on chromosome 17q12-21 between markers 42D6 and MFD188, a region 5-10 million base pairs in length. Odds in favour of linkage to this region were greater than 100,000:1 in 15 families with breast cancer. In eight families in which the probability of linkage was above 75 (range 79.2-99.9) per cent, 19 women were identified who were at high lifetime risk of breast cancer (range 80.6-87.2 per cent) and 37 whose risk was similar to that for the general population (range 9.8-16.4 per cent). Genetic risk prediction of this kind may enable high-risk screening clinic resources to be concentrated on those most likely to benefit.

Adult↗
PubMed1993

Tumour cyclic AMP binding proteins: an independent prognostic factor for disease recurrence and survival in breast cancer.

In two separate cohorts of breast cancer patients presenting without evidence of distant metastatic disease, high levels of tumour cyclic AMP binding proteins (> 8 pmol/mg cytosol protein) have been shown to be associated with poor prognosis in terms of both disease recurrence and overall survival. This association is independent of known established prognostic factors and allows the identification of a small subgroup of patients whose outlook warrants the implementation of aggressive systemic therapy.

Breast Neoplasms↗
PubMed1993

Noninvasive ductal carcinoma of the breast: the relevance of histologic categorization.

A consecutive series of 130 review-confirmed cases of noninvasive ductal carcinoma of breast (DCIS) in women without previous breast carcinoma was analyzed. Histologic variables assessed included histologic pattern, nuclear grade, necrosis, and involved duct counts. These were correlated with presentation, extent of DCIS in the breast, completeness of excision, and outcome. Comedo DCIS had an occult presentation significantly more often than noncomedo DCIS. Micropapillary DCIS was significantly more likely than other patterns to involve multiple quadrants of breast, irrespective of nuclear grade or necrosis. Solid DCIS was significantly more often completely excised when compared with all other patterns, while high-grade DCIS was significantly more often incompletely excised compared with low-grade DCIS. Follow-up showed invasive recurrence in 16% of cases treated by primary local excision only and 3% cases treated by mastectomy or with re-excision. Of local excision cases with follow-up longer than 3 years, 22% had invasive recurrence. Invasive recurrence only followed high-grade DCIS and most often followed comedo DCIS. The need for strict definition of categories of DCIS is stressed.

Adult↗
PubMed1993

The importance of interpectoral nodes in breast cancer.

In a consecutive series of 73 patients undergoing a level III axillary clearance, interpectoral nodes were sought and, if palpable, excised. 18 interpectoral nodes were identified in 15 patients, 10 (14%) of whom had involved and 5 of whom had uninvolved interpectoral nodes. 7 of the 10 patients with involved interpectoral nodes also had axillary node involvement, but 3 patients had positive interpectoral nodes in the absence of involved axillary nodes. A comparison of patient and tumour characteristics in the groups of patients with and without interpectoral node involvement showed that patients who had involved interpectoral nodes were significantly younger and had significantly larger tumours. Interpectoral node involvement by breast cancer is not uncommon and these nodes can be involved in the absence of axillary nodal involvement. They should be looked for, and if identified, excised during axillary clearance.

Adult↗
PubMed1993

Cervical intraepithelial neoplasia in patients with breast cancer: a cytological and colposcopic study.

Twenty-six patients with treated breast cancer who had been randomised previously to receive combination chemotherapy including alkylating agents (n = 14) or to undergo oophorectomy (n = 12) following surgery underwent cytological and colposcopic screening of the uterine cervix. Colposcopically directed cervical punch biopsies were taken from all patients in whom a colposcopic abnormality was detected. Breast cancer patients were compared with 79 controls with normal cervical cytology and no known breast malignancy. Colposcopically directed punch biopsies were taken from the cervical transformation zone of all controls. Significantly more breast cancer patients who had received chemotherapy (43%) than controls (10%) had CIN (P < 0.01) and significantly more patients who had received chemotherapy (14%) than controls (3%) had CIN 2 or 3 (P < 0.05). The proportion of breast cancer patients in the oophorectomy group with CIN (17%) did not differ significantly from the control group. No case of CIN was detected by cervical cytology. This study suggests that breast cancer patients receiving combination chemotherapy including alkylating agents are at increased risk of CIN, and that cervical cytology alone may be an inadequate form of screening for these patients.

Adult↗
PubMed1993

pS2 is an independent factor of good prognosis in primary breast cancer.

In breast cancer, oestrogen regulated genes, such as pS2, may be expressed in well differentiated tumours with a good prognosis. We have examined pS2 mRNA expression in 78 primary, untreated breast cancers and related pS2 expression to disease behaviour and known prognostic factors. pS2 mRNA expression was detected in 25/78 (32%) of cancers and was significantly associated with a moderate/high oestrogen receptor content (P = 0.045, Chi Square test). pS2 mRNA expression was associated with freedom from disease at median 31 months clinical and radiological follow-up (P = 0.015, Fisher's exact test, odds ratio 8.6). Using multiple logistic regression analysis of six potential prognostic factors only pathological axillary node status (P < 0.01) and pS2 mRNA expression (P < 0.05) provided independent prognostic information. Furthermore, pS2 was associated with a good prognosis in the axillary node positive patients where only 1/13 (8%) with pS2 mRNA expression compared with 13/29 (45%) without detectable expression had recurrence of their disease. These data provides strong support for pS2 as a useful independent prognostic factor in primary breast cancer.

Adult↗
PubMed1992

Excision biopsy of malignant melanoma by general practitioners in south east Scotland 1982-91.

OBJECTIVE: To examine the management of patients who had a malignant melanoma excised initially by general practitioners in south east Scotland over the past 10 years and to assess the impact of the April 1990 contract on this. DESIGN: A retrospective case-control study. SETTING: South east Scotland. SUBJECTS: All patients in south east Scotland who had malignant melanomas excised by general practitioners in 1982-91. OUTCOME MEASURES: Demographic details of patients; Breslow thickness, clearance of excision. RESULTS: 42 patients had malignant melanomas excised by general practitioners in 1982-91: 15 in 1982-9 and 27 in 1990-1. These patients were significantly younger than those who had their tumours excised initially in hospital. Although the longest diameter of melanomas excised by general practitioners was significantly less than of those excised in hospital, the Breslow thicknesses were similar. Completeness of initial excision was doubtful or incomplete in nine (23%) general practitioner excisions compared with 4% of hospital excisions, but the time interval between excision biopsy and wide excision was similar. Pathology requests accompanying excision biopsies mentioned melanoma as a possible diagnosis in 15% (6/40) of general practitioner cases compared with 79% of hospital cases. Thirty nine general practitioners responded to a questionnaire and only 12 had considered melanoma in the differential diagnosis. CONCLUSIONS: General practitioners need to think more often of malignant melanoma when they excise pigmented lesions and when they consider this tumour a possibility should perform an excision biopsy with a lateral clearance of at least 2 mm.

Adult↗
PubMed1992

p53 mutations in breast cancer.

We have identified and analyzed 41 mutations in p53 in sporadic breast tumors from 136 unselected breast cancer patients and estimate that approximately 40% of such tumors contain p53 mutations. The frequency of G-T transversions and the incidence of guanosine mutations in the nontranscribed strand of the p53 gene were found to be higher than expected, and we suggest, therefore, that exogenous carcinogens have an etiological role in sporadic breast cancers. Mutations were recorded in 44 codons of the p53 gene, with no obvious mutational hot-spots, although mutations at codons 175, 194, 273, and 280 accounted for 25% of the changes. One germ-line mutation was found in 136 patients and so we conclude that constitutional mutation of p53 may be an uncommon etiological factor in breast cancer.

Base Composition↗
PubMed1992

p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters.

The p53 locus on the short arm of chromosome 17 at 17p 13.1 was examined for loss of heterozygosity, mutation, mRNA and protein expression in 60 primary breast cancers. Allele loss around the p53 locus was detected in 19/45 informative tumours (42%). p53 mutations in the evolutionarily conserved exons 5 to 9 were detected in 17/60 (28%) by amplification mismatch and confirmed by direct DNA sequencing. p53 mRNA expression was detected by Northern blot in 36/59 (61%) of tumours, and p53 protein expression using antibody 1801 on frozen-tissue sections in 13/44 of the tumours examined. p53 mutation was significantly associated with oestrogen-receptor-poor tumours (p less than 0.01) and hence with poor prognosis, but not with other clinical or pathological parameters. There was no statistical correlation between loss of heterozygosity around the p53 locus at 17p13.1 and p53 mutation. Furthermore, p53 mutation was not associated with p53 expression detected by immunohistochemical staining with antibody 1801 or as p53 mRNA. In addition, events on 17p (allele losses, p53 mutation, p53 expression) were independent of c-erbB-2 expression. In breast cancer, by contrast with colorectal, lung and ovarian cancer, there appears to be no clear association between p53 DNA abnormalities and p53 expression.

Alleles↗
PubMed1992

Colour Doppler ultrasonography studies of benign and malignant breast lesions.

Colour Doppler scanning was carried out on 53 patients with solid, discrete breast masses. Twenty-five of 32 breast cancers and none of 21 benign lesions gave a positive scan, giving a sensitivity of 78 per cent for association with malignancy, a specificity of 100 per cent and a positive predictive value of 100 per cent. Tumours less than 1 cm in diameter and invasive lobular cancers were least likely to give a positive scan. Axillary node scans were performed in 31 of 32 patients with breast cancer with 29 undergoing an axillary staging procedure. Nine patients had a positive axillary scan and all nine had involved axillary nodes. Three patients had involved axillary nodes, but a negative axillary scan. The sensitivity of colour Doppler scanning for axillary node involvement was 75 per cent, with a specificity of 100 per cent and a positive predictive value of 100 per cent.

Adolescent↗
PubMed1992

Assessment of non-palpable mammographic abnormalities: comparison between screening and symptomatic clinics.

A retrospective study found that a breast screening clinic generated fewer localization biopsies for non-palpable mammographic abnormalities than a symptomatic clinic (3.36 versus 9.89 per 1000 mammograms, respectively) and that a greater proportion of such biopsies were malignant. This study determined the reason for this difference. There were 108 of 304 (35.5 per cent) and 17 of 130 (13.1 per cent) carcinomas in women attending the screening and breast clinics respectively (relative risk 2.72 (95 per cent confidence interval 1.70-4.34)). This difference was regardless of age. The characteristics of the mammographic abnormality, the Wolfe pattern, a family history of breast carcinoma, parity and age at first pregnancy were similar in both groups. Women attending the screening clinic were referred for localization biopsy after assessment by clinicians and radiologists at a joint clinic; there was no joint assessment for patients attending the breast clinic. The same staff attended both clinics, although the proportion of time spent at each varied. This study suggests that all women with a non-palpable mammographic abnormality should be reviewed at a joint assessment clinic before localization biopsy is recommended.

Biopsy↗