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I Mittra

Publications and source records attributed to I Mittra.

At least 37 records · Page 2Linked to original sources

Breast screening: the case for physical examination without mammography.

Many studies have shown that screening for breast cancer can reduce mortality from the disease. Mammography has come to be regarded as the screening method of choice, but evidence suggests that physical examination (PE) is at least as effective in reducing mortality. Mammography detects many non-infiltrating and small, non-palpable tumours, but we do not know whether these would ever cause symptoms or threaten the woman's life. It is doubtful whether the time gained by early mammographic detection confers any survival benefit over PE detection. PE has substantial advantages over mammography in terms of human and economic costs. The question we should be asking is not how to refine mammographic screening but whether we need it at all.

Adult↗

Prognostic association of c-erbB-2 oncogene amplification and protein overexpression in human breast cancer using archival tissues. A comparative study.

The prognostic associations of c-erbB-2 gene amplification analysed by dot-blot hybridization and of c-erbB-2 protein overexpression assessed by immunohistochemistry (IHC) were compared in 161 patients with operable breast cancer using formalin fixed paraffin embedded archival tissues. The efficiency of the dot-blot technique to detect c-erbB-2 amplification was first validated by comparing the results of dot-blot with those of Southern blot hybridization in 134 tumour samples and there was an excellent correlation. In the main series of 161 samples, where results of IHC and dot-blot were compared, 35.4% showed c-erbB-2 overexpression and 17.4% showed gene amplification. Tumours showing overexpression of c-erbB-2 protein had a significantly shorter disease-free survival (DSF) and survival(s) compared to tumours showing no overexpression. A multivariate analysis revealed that c-erbB-2 overexpression was independently correlated with poor prognosis. On the other hand, no significant association between c-erbB-2 gene amplification and DFS or S was observed. We conclude that c-erbB-2 protein overexpression assessed by IHC is a superior prognostic indicator in operable breast cancer compared to c-erbB-2 gene amplification analysed by the dot-blot technique.

Blotting, Southern↗

Prognosis of operable squamous cell carcinoma of the esophagus. Relationship with clinicopathologic features and DNA ploidy.

BACKGROUND: Reports on the influence of various prognostic factors in carcinoma of the esophagus are conflicting. The prognostic value of a set of clinicopathologic factors and DNA ploidy were examined in 74 patients with surgically resected squamous cell carcinoma of the lower and middle third of the esophagus. METHODS: All patients had surgery performed in a single thoracic surgical unit at the Tata Memorial Hospital between January, 1984 and December, 1987. The clinicopathologic factors studied were (1) gross residual disease at operation; (2) morphology of the tumor; (3) depth of microscopic invasion; (4) lymph node involvement; (5) histologic grade; (6) vascular and lymphatic embolism; and (7) sex. DNA ploidy and S-phase fraction (SpF) were determined by flow cytometry on archival tissues extracted from paraffin blocks. Ploidy status could be determined successfully in all 74 tumors, whereas SpF could be assessed only in 25. RESULTS: Of the various prognostic factors examined with the Cox stepwise regression model, residual disease (P = 0.000), depth of invasion (P = 0.047), and lymph node status (P = 0.077) were found to be correlated with overall survival. CONCLUSIONS: DNA ploidy was not related to prognosis. The overall survival of this group of patients at 36 months was 28%, and median survival was 18 months.

Carcinoma, Squamous Cell↗

Oestrogen and progesterone receptor estimation by enzyme-immunoassay on tissues removed before and after a modified radical mastectomy.

To investigate the possibility of receptor degradation due to devascularization of the tumour during mastectomy, oestrogen and progesterone receptors (ER and PgR) were measured by an enzyme-immunoassay (EIA) in 59 cases of primary breast cancer on samples taken before and after performing a modified radical mastectomy. Pre- and post-mastectomy samples from the same patient were analysed simultaneously in the same assay run. There was 86.4% and 93.2% agreement respectively in ER and PgR status between samples removed before and after surgery. When actual values were analysed, the post-mastectomy values were higher or lower than pre-mastectomy values with similar frequency. These random variations could be attributed to heterogeneous distribution of receptors within a tumour. The overall correlation between pre- and post-mastectomy values was excellent (ER: r = 0.810, P < 0.001; PgR: r = 0.706, P < 0.001). Devascularization of the tumour during surgery does not seem to affect the integrity of the epitopes recognized by monoclonal antibodies against ER and PgR to any significant extent.

Breast Neoplasms↗

Correlations between c-erb beta-2 oncogene amplification and the expression of its mRNA and protein in human breast carcinomas.

Nineteen human breast tumours were analysed for c-erb beta-2 gene amplification, the over-expression of its mRNA and the production of its protein residue by southern blot, northern blot and western blot technique respectively. Protein expression was also assessed by immunohistochemistry on paraffin sections, c-erb beta-2 gene amplification was found in 6 of 19 (31%) tumours. Over-expression of c-erb beta-2 mRNA was found in 7 of 19 (37%) tumours. Expression of the 185 kd c-erb beta-2 protein product was detected in 3 of 19 (16%) tumours by western blotting and in 5 of 19 (26%) by immunohistochemistry. In only 4 tumours with an amplified c-erb beta-2 gene was there a clear association between all three parameters. In view of the conflicting reports in the literature concerning c-erb beta-2 gene amplification or protein over-expression (assessed by western blot or immunohistochemistry) and prognosis of breast cancer, studies in which these parameters are correlated individually with prognosis in the same group of patients are needed.

Breast Neoplasms↗

DNA analysis of breast cancer by flow cytometry & correlation with other prognostic parameters.

Flow cytometric estimation of DNA content (ploidy and S-phase fraction--SpF) was done on breast cancer tissues from 171 patients. Twenty eight per cent of the tumours were diploid and 72 per cent were aneuploid. SpF was measurable in 82 DNA histograms; of these 22.4 per cent had SpF less than 10 per cent, 34.1 per cent had SpF between 10-20 and 43.5 per cent had SpF greater than 20 per cent. The mean SpF of the measurable histograms was 19.01 per cent with a range 1.78 to 45.19 per cent. A significant correlation between DNA ploidy and SpF was observed (P less than 0.01). Eighty nine per cent of diploid tumours had SpF less than 10 per cent and 73 per cent of aneuploid tumours had SpF greater than 20 per cent. A significant correlation was also found between ploidy and SpF and oestrogen receptor (ER) status of the tumours (P less than 0.05) and between SpF and progesterone receptor (PgR) status of the tumours (P less than 0.05), but not between ploidy and PgR status of the tumours. A significant direct correlation was observed between SpF and tumour grade (P less than 0.05), but not between ploidy and tumour grade. No correlation was observed between DNA ploidy and SpF and tumour type, tumour size, axillary lymph node involvement, age and menopausal status of the patients. Although the incidence of breast cancer is one-third of that reported in the Western countries, there is apparently no biological difference between the various parameters studied.

Aneuploidy↗

Estrogen & progesterone receptors measurement in breast cancer with enzyme-immunoassay & correlation with other prognostic factors.

Estrogen and progesterone receptor (ER and PgR) estimation was carried out by an enzyme-immunoassay by a 'sandwich' technique using two different monoclonal antibodies against each receptor on 508 consecutive breast cancer samples. 43.9 per cent of the tumours were ER+ve and 26.6 per cent were PgR+ve; 23.8 per cent were both ER and PgR+ve, 53.3 per cent were both ER and PgR-ve, 20.0 per cent were ER+ve PgR-ve and 2.8 per cent were ER-ve PgR+ve. Both ER and PgR positivity was associated with increasing age, and this was seen within both pre and post-menopausal subgroups. Grades I and II tumours were more often ER and PgR+ve compared with grade III tumours, indicating that receptor positivity is a marker of a more well differentiated tumour phenotype. Receptor positivity was higher in primary tumours compared to that in metastatic tissues. The proportion of tumours that was ER+ve was found to vary among the four major religious communities, viz., Hindu, Muslim, Christian and Parsi, and this variation was significant in the overall analysis (P less than 0.01). The Christians had the highest rate of ER+ve tumours while the Muslims had the lowest rate. No correlation was observed between ER and PgR status and axillary nodal involvement or tumour size, suggesting that ER and PgR are independent prognostic factors in breast cancer. We found the EIA method to be an easy and rapid technique for ER and PgR analysis and which requires a small amount of tissue and does not involve the use of radioisotopes.

Adolescent↗

A meta-analysis of reported correlations between prognostic factors in breast cancer: does axillary lymph node metastasis represent biology or chronology?

A statistical overview of published results on correlations between various prognostic factors in breast cancer was undertaken. A distinction was made between clinical (or anatomical) prognostic factors--namely, axillary lymph node status and tumour size--and eight different biological prognostic factors. The latter included: tumour grade, oestrogen and progesterone receptor status, thymidine labelling index, DNA ploidy, S-phase fraction, epidermal growth factor receptor expression and c-erbB-2 gene amplification (or overexpression). 139 articles were eligible for review which reported a total of 432 individual correlations. A simple form of meta-analysis was employed: the counting method, in which the number of studies achieving a statistically significant correlation or not were counted. For each possible correlation examined, the proportion of studies showing a statistically significant correlation was calculated and an exact binomial 99% confidence interval determined for that proportion. If the 99% confidence interval included 5% (the proportion of correlations that would be expected to be statistically significant if the null hypothesis was true), it was taken as failing to exclude the null hypothesis of a zero correlation, while if it excluded 5% it was taken as rejecting the null hypothesis of a zero correlation. A broad agreement was found among published reports on the existence of a statistically significant correlation between the various biological prognostic factors in breast cancer. Of the 20 correlations examined, 18 had a 99% confidence interval excluding 5%, thus rejecting the null hypothesis of a zero correlation. On the other hand, a completely different result was obtained when reports on possible correlations between lymph node status and tumour size on the one hand and the eight biological prognostic factors on the other were analysed. Of the 16 correlations examined, 13 had a 99% confidence interval including 5%, failing to reject the null hypothesis of a zero correlation. These observations suggest the hypothesis that the prognostic influence of node status and tumour size cannot be explained by an analysis of the biology of breast cancer; and is compatible with the contention that axillary node status is merely a reflection of the relative chronological age of breast cancer.

Breast Neoplasms↗

A comparative study of dextran coated charcoal (DCC) and enzyme immunoassay (EIA) methods for oestrogen receptor (ER) estimation in breast cancer.

Oestrogen receptor (ER) concentrations were measured in 100 breast cancer cytosols using both the dextran coated charcoal assay (DCC with 6--point scatchard plot) and a newly developed enzyme linked immunoassay (EIA) using a monoclonal antibody against ER. The efficiency of the two methods was compared. A highly significant correlation was observed between the ER levels determined by DCC and EIA methods (r = 0.94, p less than 0.001). The mean ER-EIA value (43.25 +/- 74.77) was, however, significantly higher than the mean ER-DCC value (18.00 + 37.27) (p less than 0.001); in both pre- menopausal (p less than 0.001) and post-menopausal (p less than 0.001) groups. Using a cut-off point at 10 fmo/mg protein for ER-EIA and 3 fmol/mg protein for ER-DCC/to distinguish ER +ve and -ve tumours, a 97% concordance between the two assays was achieved. The EIA method appears to be preferable to the DCC method because it is easy to perform, rapid, requires less tissue and does not involve the use of radioactive substances.

Breast Neoplasms↗

Differences in oestrogen receptor status and histological grade of breast cancer in different religious communities in Bombay.

The various religious communities in India viz.Hindu, Muslim, Christian, Parsi have different breast cancer incidence rate. It is not known whether there might also exist differences in biological properties of breast cancer between these communities. To investigate this possibility we have studied the distribution of oestrogen receptor (ER) status and histological grade of tumour in these four communities. Significant differences were observed in the overall distribution of ER positivity and histological grade between the communities P less than for both parameters). Christians had the highest incidence of ER +ve (65.2%) and grade I + II tumours (16.0%), while Muslims had the lowest incidence of ER +ve (35.8%) and Grade I + II tumours (4.7%). In general, we found a significant positive relationship between ER status and age of the patient (p less than 0.0.1). The mean age of the christians was slightly but significantly higher than that of the Hindus and Muslim. The difference ER positivity between the communities might, therefore, be partly (but probably not wholly) explained by difference in age of the patients. However, the difference with respect to grade of tumour cannot be explained as a function of age since no significant association was found between grade of the tumour and age of the patient. Further investigation with respect to difference in the biology of the breast cancer between the communities are warranted.

Adult↗

Clinico-pathological features and prognosis of breast cancer in different religious communities in India.

A study of clinical and pathological features, patterns of relapse and prognosis of breast cancer in various religious communities--viz. Hindu, Muslim, Christian and Parsi--was undertaken among 4377 evaluable cases treated at Tata Memorial Hospital between 1965 and 1982. Of these 82.4 per cent were Hindus, 7.3 per cent Muslims, 7.4 percent Christians and 2.7 percent Parsis. The mean age at diagnosis was 55 years for Parsis which was 7 to 8 years older than that for the other communities. There were no remarkable differences in histological tumour type or grade; except that parsis had higher incidence of uncommon histological types, such as dust carcinoma in situ and colloid carcinoma, and had a slightly more favourable grade distribution. When classified according to the TNM system (UICC 1978), the Parsis had the most favourable stage at presentation followed by Christians, Hindus and Muslims in that order. This trend was highly statistically significant (p less than 0.001). Despite this significant differences between stage of disease at diagnosis, no differences in the overall 5-year survival was observed between the communities. This remained true even after matching for disease stage and menopausal status. Even the Parsis, in whom the disease was detected relatively early, failed to register a survival advantage. Much work need to be done with regard to early detection of Breast Cancer in India.

Adult↗

Clinical significance of serum spermine in breast cancer.

The diagnostic significance of three polyamines (putrescine, spermidine and spermine), of carcinoembryonic antigen and of phosphoglucose isomerase have been compared in sera of patients with breast cancer or benign breast disease and normal age matched controls. The results of the study indicate that the performance of spermine was more striking than that of any of the other markers. The estimation of spermine may prove to be a valuable parameter not only in detection but also in prediction of recurrence of the disease.

Adult↗

Unique monoclonal antibodies against soluble membrane proteins of human CML myelocytes reactive with human myeloid progenitor cells.

Monoclonal antibodies of IgG1 type immunoglobulin, directed against soluble CML antigen isolated from the reactive CML peripheral myelocytes, were reported. These MAbs were further investigated for their reactivity by 125I-Protein-A binding assays, indirect immunofluorescence tests, cytotoxicity, SDS-PAGE, immunoelectrophoresis, and by immunodiffusion suggesting that they recognized antigens specific mostly to undifferentiated cells. These were tested against various leukemic peripheral blood leukocytes, bone marrow cells, established cell lines of various origin, and with many solid tumor cells and demonstrated specific reactivity with CML myelocytes alone and cell lines of myeloid origin. Indirect immunoperoxidase staining of single cell preparation revealed peroxidase localization in most promyelocytes and in few mature myelocytes from CML PBL/BM cells, thus helping in identifying the exact type (morphology) involved in reacting specifically with these MAbs.

Antibodies, Monoclonal↗