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Biomedical subjects

R Anbazhagan

Publications and source records attributed to R Anbazhagan.

27 records · Page 2Linked to original sources

Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group.

PURPOSE: To evaluate the prognostic importance of immunocytochemically determined c-erbB-2 overexpression in the primary tumors of patients with breast cancer. PATIENTS AND METHODS: Primary tumors from 1,506 breast cancer patients (760 node-negative and 746 node-positive) who were treated in the International (Ludwig) Breast Cancer Study Group Trial V were studied. Node-negative patients were allocated randomly to either a single cycle of perioperative chemotherapy (PeCT) or no adjuvant treatment, and node-positive patients received either a prolonged chemotherapy (with tamoxifen for postmenopausal patients) or a single perioperative cycle. RESULTS: Tumors from 16% of the node-negative patients and 19% of the node-positive patients were found to be c-erbB-2-positive. In both groups c-erbB-2 positivity correlated with negative progesterone receptors (PR), negative estrogen receptors (ER), and high tumor grade. Lobular carcinomas were all negative, and, thus support the view that such tumors represent a defined subtype of breast carcinoma. The expression of c-erbB-2 was prognostically significant for node-positive but not for node-negative patients. However, in both subgroups, the prognostic significance was greater for patients who had received more adjuvant therapy. For node-positive patients, the effect of prolonged-duration therapy on disease-free survival (DFS) was greater for patients without c-erbB-2 overexpression (hazards ratio [HR], = 0.57; 95% confidence interval [CI], 0.46 to 0.72) than for those with c-erbB-2 overexpression (HR, 0.77; 95% CI, 0.51 to 1.16). Similarly, for node-negative patients, the effect of PeCT on DFS was greater for those without c-erbB-2 overexpression (HR, 0.82; 95% CI, 0.61 to 1.09) than for those with c-erbB-2 overexpression (HR, 1.22; 95% CI, 0.66 to 2.25). CONCLUSION: We conclude that tumors with overexpression of the c-erbB-2 oncogene are less responsive to cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant therapy regimens than those with a normal amount of gene product.

Adult↗

Growth and development of the human infant breast.

Seventy-two samples of infant breasts, aged from newborn to 2 years, were collected at necropsy. Whole-mount preparations and histological sections were made. A system of classification was devised to study the extent of the structural development of the ductal system (morphological types I, II, and III) and the functional differentiation of the lining epithelium (functional stages I to V). There was no correlation between the age of the infant and the type of development of the ductal system. In contrast, the epithelial differentiation followed a chronological pattern, starting with secretory changes and apparently going through a period characterized by apocrine metaplasia before post-secretory involution. These epithelial changes were not associated with the morphological type of the ductal system. There were no distinguishing features between the breasts from the two sexes. Immunoperoxidase staining for actin and kappa-casein was carried out to study the myoepithelial cells and secretory cells, respectively. Myoepithelial cells were present at all stages and prominent staining for casein was observed up to 2 months of age. Embryonic-type adipose tissue was seen in 7 cases, in one of which it was associated closely with the developing ductal system. Extramedullary hematopoiesis was observed in the periductal connective tissue until 4 months of age. This paper describes the most extensive anatomical and histological study of the human infant breast to date and lays the foundation for a detailed study of the epithelial and stromal changes that take place during human breast development.

Actins↗

Association of c-erbB-2 expression and S-phase fraction in the prognosis of node positive breast cancer.

An immunohistochemical study was performed on 211 primary breast carcinomas for c-erbB-2 expression. All patients had involvement of axillary lymph nodes and all were randomised onto one of the Ludwig Breast Cancer Trials I-IV between July 1978 and August 1981. c-erbB-2 overexpression significantly correlated with high S-phase fraction, four or more positive axillary nodes involved, estrogen receptor negative primaries, progesterone receptor negative primaries, high grade tumours and DNA aneuploidy. With a nine year median follow-up c-erbB-2 positive tumours had worse disease-free survival (p = 0.0002) and overall survival (p less than 0.0001). Multivariate analyses using proportional hazard regression models demonstrated that c-erbB-2 positivity continued to predict a poor outcome even when accounting for the effects of other prognostic factors.

Antibodies, Monoclonal↗

Expression of p53 in premalignant and malignant squamous epithelium.

Using three antibodies (JG8, CM-1 and 1081) directed to the p53 protein, strong positivity was found in 16/47 (34.0%) of mucosal squamous cell carcinomas of the head and neck and in two squamous carcinoma cell lines (LICR-LON- HN5 and HN6Rr). The presence of the mutant p53 was confirmed in the cell lines as substitutions in exon 7 (codon 238, TGT greater than AGT) and exon 5 (codon 152, CCG greater than CTG) respectively. Positive staining was seen only in the undifferentiated cells and progressively lost as the cells keratinized, both in the tumour specimens and in the cell lines. Similar results were seen in areas of dysplasia, well removed from the site of the primary tumour. Staining of epidermal lesions showed positivity in 2/12 (16.6%) cases of Bowen's disease, 0/12 (0.0%) cases of solar keratosis, 0/10 (0.0%) basal cell carcinomas and in 3/20 (15.0%) squamous cell carcinomas. These results are discussed in relation to the multifocal origin of squamous cell carcinomas, the role of p53 mutations in squamous cell carcinomas from different sites and the significance of the 'basal' distribution of p53 as a normal growth regulator. The possible significance of the distribution of p53 in squamous epithelium as it relates to papilloma virus infection is also considered.

Amino Acid Sequence↗

The distribution of immuno-reactive tenascin in the epithelial-mesenchymal junctional areas of benign and malignant squamous epithelia.

Tenascin is an extra cellular matrix glycoprotein which is distributed in the mesenchyme surrounding various organs during embryogenesis. It has also been demonstrated in some normal adult tissues and in the matrix of human tumours. The present study has been carried out to analyse the distribution of tenascin in non malignant and malignant skin disorders, in squamous cell carcinomas of the head and neck, in squamous cell carcinoma xenografts and in a squamous cell carcinoma cell line grown on collagen gel. Immunohistochemical localisation of tenascin was performed, using a monoclonal antibody specific for tenascin, by the indirect immunoperoxidase method with silver enhancement. Tenascin was heterogeneously distributed in the extra cellular matrix of squamous cell carcinomas and in squamous cell carcinoma xenografts. It was absent in basal cell carcinoma and in the squamous cell carcinoma cell line grown on collagen gel. The distribution of tenascin in squamous cell carcinoma and basal cell carcinoma is discussed in relation to tumour invasion and differentiation.

Animals↗