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Biomedical subjects

R R Millis

Publications and source records attributed to R R Millis.

At least 91 records · Page 5Linked to original sources

Immunohistochemical study of D5 antigen (an oestrogen receptor related protein) in normal breast, benign breast disease, and mammary carcinoma in situ.

Patterns of staining with a monoclonal antibody which recognises D5 antigen (a 29,000 kD oestrogen receptor-related protein) were studied in seven normal and 76 benign breast biopsy specimens as well as in 12 cases of pure in situ mammary carcinoma. Staining in benign breast lesions was weak and heterogeneous when compared with that seen in most infiltrating carcinomas. In situ carcinomas showed an intermediate pattern of staining. The finding of only small foci of weak positivity for D5 antigen in normal and benign breast disease indicated that there are similarities between the expression of D5 antigen and the presence of oestrogen receptor protein in these tissues. A further similarity was seen with in situ carcinomas, which have been shown to have lower oestrogen receptor content than infiltrating carcinomas and a more heterogeneous staining pattern with D5 than is seen in infiltrating tumours. The importance of these findings remains to be evaluated because the precise nature of D5 antigen and its association with the oestrogen receptor molecule is not fully understood.

Adolescent↗

Characterization and biological relevance of a 29-kDa, oestrogen receptor-related protein.

The properties of a monoclonal antibody (D5) that can immunoprecipitate human oestradiol receptor (ER) under some but not all conditions are described. The antibody recognises a 29-kDa serine phosphoprotein that is qualitatively and quantitatively related to ER but not other steroid receptors or binding proteins. p29 will not complex with untreated cytosol ER but, after ammonium sulphate, KCl, heat or phosphatase treatments, interaction occurs that can be detected by immunoprecipitation with D5; molybdate and GTP inhibit complex formation. In human endometrium, p29 is increased by oestrogen and decreased by progestins. IRMA and histochemical assays for p29 have been developed and applied to a large series of human breast tumours. Most, but not all ER+ tumours are p29+, whilst ER-tumours are rarely p29+ unless they are also PR+. p29 predicts for clinical response to hormone therapy. ER+ p29+ tumours have a higher response rate than the ER+ p29-tumours. We do not know if p29 is a previously undetected component of the oestradiol receptor machinery or whether it is a product of oestrogen action.

Antibodies, Monoclonal↗

Acetylator status and its relationship to breast cancer and other diseases of the breast.

The distribution of N-acetylation phenotypes has been investigated in 410 consecutive patients prior to diagnostic excision of a breast lump and compared to that in 337 healthy controls. Contrary to previously published data there was no excess incidence of fast acetylators in patients with malignant breast disease. There was, however, a significant trend for more rapid acetylator ratios to be associated with advanced disease at first presentation. There was a slight but non-significant excess of fast acetylators in patients with benign breast disease as compared to controls, but there were no significant differences in the proportion of the acetylator phenotypes between cystic breast diseases with or without epithelial hyperplasia. There were no significant associations between oestrogen and progestogen receptors and the acetylator phenotype. It is concluded that the acetylation phenotype has no important association with malignant breast disease.

Acetylation↗

Histological grade, elastosis, DNA ploidy and the response to chemotherapy of breast cancer.

The relationships between response to chemotherapy of advanced breast cancer and the histological type, grade, elastosis content and DNA ploidy of the primary tumours were examined using paraffin-embedded tissue derived from 125 patients. Higher response rates were seen amongst tumours with a high elastosis content and those that were diploid. However, selection of patients with advanced breast cancer for chemotherapy will not be assisted significantly by an assessment of these features in the primary tumour.

Aneuploidy↗

Binding of oestradiol to blood proteins and aetiology of breast cancer.

A prospective study of 5,000 women has shown that, compared to controls, those who subsequently developed breast cancer had a higher proportion of their blood oestradiol in the non-protein-bound and albumin-bound fractions (the bio-available fraction) and a lower proportion in the sex-hormone-bound fraction. The increased proportion of bio-available oestradiol was partly due to a lower concentration of sex-hormone-binding globulin. Weight was excluded as a confounding factor.

Adult↗

The significance of supraclavicular fossa node recurrence after radical mastectomy.

The clinical and pathologic features of 35 patients who had ipsilateral supraclavicular node (SCF) recurrence after radical mastectomy were reviewed. These were compared with the features of 70 patients who had a local skin recurrence after radical mastectomy, 48 of whom had a single nodule and 22 of whom had multiple skin nodules. There were no significant differences between age at diagnosis, disease-free interval, menstrual status, tumor type and grade, and extent and location of axillary node metastases in the three groups. Survival of the SCF group was intermediate between those of the single-nodule and multiple-nodule groups. SCF recurrence is an almost invariable signal of micrometastatic disease; thus, such patients are ideal candidates for trials of adjuvant therapy.

Actuarial Analysis↗

Effect of the method of biopsy on the prognosis of and reliability of receptor assays in patients with operable breast cancer.

A comparison has been made of the survival of contemporary patients treated by mastectomy in whom the original diagnosis was made by either Tru-cut biopsy or by excision biopsy. After a minimum of 5 years of follow-up there was no difference in survival between those biopsied by either method. When subdivided by tumour size again no differences emerged. Among those patients in whom the original Tru-cut biopsy was false negative there was no difference in survival compared with those treated by excision biopsy. This suggests that Tru-cut biopsy is a safe method for obtaining a histological diagnosis in operable breast cancer. Furthermore, when the receptor status of the tumours from the two groups was determined, there was no difference in the percentage of oestrogen receptor positive tumours, nor in the mean receptor value. However, there were more progesterone receptor positive tumours among the Tru-cut group, suggesting that a better tumour sample could have been submitted for analysis. This may be yet another advantage for the use of Tru-cut biopsy for the diagnosis of breast cancer.

Biopsy↗

Paget's disease of the nipple: a ten year review including clinical, pathological, and immunohistochemical findings.

Thirty-five women with biopsy-proven Paget's disease of the nipple were treated over a 10 year period at the Breast Cancer Unit, Guy's Hospital. Twenty-four (69%) patients had Paget's disease without a palpable mass in the breast; eleven (31%) presented with a palpable mass and Paget's disease of the nipple. Definitive treatment consisted of modified radical mastectomy in 32 patients, radiotherapy only in 2, and one patient had no definitive treatment. All 11 patients with Paget's disease and an associated lump proved to have invasive ductal carcinoma; five also had associated positive axillary nodes. Nine of the 23 patients with nipple changes only, treated by mastectomy, also had invasive carcinoma; three of these had positive axillary nodes. The remaining 14 patients with nipple changes only were found to have in situ ductal carcinoma, which was extensive in the majority of cases. In 13 cases, histological sections of the nipple were examined by immunohistochemical staining which showed that the Paget's cells expressed a keratin phenotype that was specifically characteristic of simple epithelial cells as seen in glandular epithelium. This was quite unrelated to the normal keratin phenotype of the surrounding skin keratinocytes. Clinical, pathological, and immunohistochemical data suggest a mammary origin of the abnormal cells in Paget's disease of the nipple. Mastectomy appears to be the treatment of choice.

Adult↗

Response to endocrine therapy and breast cancer differentiation.

The purpose of this study was to determine whether aspects of tumour differentiation are associated with response to endocrine therapy in patients with advanced breast cancer. The features studied were the histological type, grade, and elastosis content of the primary tumours, and the disease-free interval. Statistically significant associations were observed between response to endocrine therapy and histological grade and disease-free interval. In addition, statistically significant associations were observed between histological grade and elastosis and disease-free interval. It is concluded that tumours which are more highly differentiated have a better chance of responding to endocrine therapy.

Androgens↗

Serum prolactin levels in women with breast cancer and their relationship to survival.

Serum prolactin (HPr) has been measured in 459 patients 1 day before (HPr-1) and in 433 patients 10 days after (HPr-2) treatment. These came from an unselected sequence of 739 patients with operable breast cancer who had been referred to Guy's Hospital over a period of 5 yr. In addition HPr was measured in 100, or more, women at 3, 6 or 12 months after mastectomy. The median levels of either HPr-1 or HPr-2 were higher in pre-menopausal compared with postmenopausal patients (P = 0.03 and 0.06, respectively). Mastectomy was associated with increased serum HPr in both pre- and post-menopausal patients (P less than 0.001 in both cases). Average levels at 3 months, or after, were similar to those found before treatment. Nulliparous women had a higher median amount of HPr-1 than parous which was significant in premenopausal patients (P less than 0.008) whilst HPr-2 levels were not related to parity. Thus the rise in HPr associated with surgery was greater in parous than nulliparous women. Prolactin levels were not related to nodal status or tumour size. However, the amounts of HPR-2 were significantly greater in women with histological grade 3 tumours than those with grade 1 or 2. Standardising for either nodal status, tumour size or histological grade seven situations were found in which HPr-1 or HPr-2 levels were of prognostic significance. Although some of these significant associations could be fortuitous all shared a common feature that the least favourable prognosis was associated with the highest HPr levels.

Adult↗

Acantholytic variant of squamous-cell carcinoma of the breast.

Three cases of acantholytic squamous-cell carcinoma of the breast are reported. They all had histological features resembling those of angiosarcoma or adenocarcinoma. They were not angiosarcoma, since in all three cases areas of squamous differentiation were present; in addition, the neoplastic cells were negative when stained for factor VIII, but were positive with anti-epidermal keratin. The glandular pattern exhibited, especially in Case 2, was difficult to differentiate from that of an ordinary carcinoma. However, the presence of dyskeratotic cells within the lumina, and the absence of alcian blue/periodic acid-Schiff positive material, and epithelial membrane antigen staining, were evidence against the diagnosis of adenocarcinoma. The patients died 5, 6, and 16 months after the diagnosis. Tumors with these histological features may have a very aggressive clinical course.

Aged↗

In situ ductal carcinoma of the breast: implications of disease pattern and treatment.

Ninety-seven patients with in situ ductal carcinoma (DCIS) of the breast have been reviewed. The commonest presenting feature was a breast lump, and residual carcinoma was found in the mastectomy specimen in 63% of patients. Furthermore, 13 cases had evidence of infiltrating carcinoma when the mastectomy specimen was examined. Thus excision alone would have left residual in situ or infiltrating carcinoma in two-thirds of the cases. A wide excision, by removing local residual disease, would still have left multifocal disease in one-third of cases. Studies need to be conducted to determine whether conservative treatment of DCIS can yield results which are as good as those following total mastectomy.

Adult↗

Histochemical studies with an estrogen receptor-related protein in human breast tumors.

The histochemical characteristics of a Mr 29,000 phosphoprotein related to estradiol receptor are described in a large series of human breast tumors. The antigen was detected with a monoclonal antibody (D5) raised against partially purified human myometrial estradiol receptor. An indirect immunoperoxidase method was used with methacarn-fixed, wax-embedded sections. Quantitation of staining and its reproducibility are described. Results with trucut biopsies agree with those obtained with larger tumor sections. Normal breast is infrequently positive. Histochemical staining is higher in invasive carcinoma than in normal breast with ductal carcinoma in situ adjacent to infiltrating tumors exhibiting intermediate values. Furthermore, most in situ carcinomas have a heterogeneous staining pattern. About 20% of invasive tumors also exhibit heterogeneity. No simple correlation is seen between staining and histological grade. There are more low-staining tumors in young (less than 50 yr old) patients than in older women. Staining correlates with levels of cytosol estradiol receptor but not cytosol progesterone receptor. However, cytosol estradiol receptor-negative, cytosol progesterone receptor-positive tumors tend to have positive Mr 29,000 phosphoprotein levels. Positive staining is associated with a higher response rate to hormone therapy (50%). None of the negative tumors responded to hormone treatment. With these patients, comparison of histochemical assay for Mr 29,000 phosphoprotein and [3H]estradiol binding assays indicated that the former was at least as good as the latter assay in predicting hormone response. About 20% of cytosol estradiol receptor-positive tumors have low Mr 29,000 phosphoprotein, and such tumors have poor response to hormone treatment.

Adult↗

Apocrine carcinoma of the breast. A morphologic and immunocytochemical study.

The mode of recognition and hence the frequency of apocrine differentiation in breast carcinomas, assessed on purely morphologic grounds, remains uncertain. One hundred consecutive cases of breast carcinoma were studied in order to establish the incidence of this type of tumor. With the use of an immunocytochemical method for the detection of GCDFP-15, a protein present in apocrine epithelium and in the fluid of tension cyst of the breast, the presence of apocrine differentiation was confirmed in 4 cases initially diagnosed as apocrine carcinomas on histologic grounds. Eight additional cases contained immunoreactive cells: 1 contained 10% of positive cells scattered throughout the tumor, and the other 7 cases were only focally positive. In 4 of these latter cases positive staining was confined to the in situ component. The ultrastructural findings in 2 cases of apocrine carcinoma are discussed in order to link the morphologic features for recognizing this tumor type and the presence of the antigenic apocrine marker.

Adult↗

Influence of reproductive history on age at diagnosis of breast cancer and prognosis.

The effect on age at breast cancer diagnosis of age at menarche, age at first baby, parity and age at menopause has been determined for 739 unselected patients diagnosed between 1975 and 1980 as having operable breast cancer. Age at diagnosis was significantly and positively associated with ages at menarche, first baby and menopause. The average number of children significantly declined with increasing age at diagnosis. This was largely due to a change in the proportion of patients who were nulliparous (15% in women aged 41-50 years compared to about 30% in those over 60 years). A group of 1,989 normal women whose reproductive history was also collected between 1975 and 1980 showed similar trends between age and age at menarche, age at first baby and parity as the patients. Thus it appears that these reproductive parameters do not alter the time of onset of breast cancer but could be explained by temporal changes in reproductive patterns. There was no significant correlation between age at menopause and age at diagnosis for patients whose age at menopause was no more than 54 years and age at diagnosis no less than 55 years, respectively. It is therefore unlikely that age at menopause affects age at diagnosis. Postmenopausal patients with 3 or more children had a significantly shorter disease-free interval and lower survival rate than those with less children. None of the other parameters was associated with prognosis.

Adult↗