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Biomedical subjects

R R Millis

Publications and source records attributed to R R Millis.

At least 37 records · Page 2Linked to original sources
PubMed1997

Angiogenesis and inflammation in invasive carcinoma of the breast.

AIM: To investigate the relation between angiogenesis and inflammation in invasive carcinoma of the breast. METHODS: Sections from 75 invasive carcinomas of the breast were stained using immunohistochemistry for von Willebrand factor, CD3, CD8, CD45RO, CD45RA, CD20, CD68, and c-erbB-2. Tumour vascularity was assessed by counting vessels in the three most vascular areas, and calculating the average (x 400 magnification, field 0.168 mm2). Each pattern of inflammation was scored semiquantitatively. RESULTS: The main pattern of inflammation was a diffuse infiltrate of macrophages, and to a lesser extent T cells. Perivascular and perilobular clusters of B and T cells were noted at the edge of the carcinomas, but were less prominent than the diffuse inflammation. Diffuse inflammation, particularly macrophages, was associated with high tumour grade, tumour necrosis, large tumour size, and c-erbB-2 expression. Perivascular and perilobular inflammation also increased with tumour grade. Tumour vascularity increased slightly with intensity of diffuse inflammation (Spearman's rank correlation coefficient rs = 0.17, p = 0.08), and was inversely related to perilobular inflammation (rs = -0.23, p = 0.03). CONCLUSIONS: The correlations between inflammation and vascularity were weak in this study (r2 about 0.04) and thus there was no evidence of an important relation. Discrepancies between this and other studies may be resolved by studying expression of angiogenic cytokines and proteolytic enzymes by tumour infiltrating inflammatory cells, and their relation to tumour vascularity.

Breast Neoplasms↗
PubMed1996

A comparative immunohistochemical study of mammary and extramammary Paget's disease and superficial spreading melanoma, with particular emphasis on melanocytic markers.

A comparative immunohistochemical study was performed on Paget's disease of the nipple (PDN), extramammary Paget's disease (EMPD) and cutaneous superficial spreading melanoma (SSM) using antibodies to S100, NK1-C3 and HMB45, cytokeratin (CAM 5.2) and c-erb B2 oncoprotein (21N). Conventional histochemical stains for intracytoplasmic mucin and melanin were also done. Of the 20 cases of PDN, positivity was seen in 12 with S100, 16 with NK1-C3, none with HMB45, 20 with CAM 5.2 and 19 with 21N. All 5 cases of EMPD were CAM 5.2 positive and HMB45, S100 and 21N negative. Three EMPD were NK1-C3 positive. All 10 cases of SSM were S100, NK1-C3 and HMB45 positive and all were CAM5.2 and 21N negative. Mucin was demonstrable in 11 cases of PDN and all of EMPD but none of SSM. Melanin was seen in 2 PDN, 3 EMPD and all SSM cases. Identification of mucin and melanin, therefore, proved an unreliable means of distinguishing these diseases. Immunohistochemistry for cytokeratin and HMB45 appear to be the most specific markers in differentiating Paget's disease and SSM. Antibodies to c-erb B2 may also be valuable in this situation.

Biomarkers↗
PubMed1996

Inflammatory infiltrate in invasive lobular and ductal carcinoma of the breast.

The significance of inflammation in carcinoma of the breast is controversial. Little attention has been paid to different patterns of inflammation or inflammation associated with different histological types of carcinoma. We have looked at the pattern of inflammation in 123 invasive mammary carcinomas (including 46 lobular), and characterised the inflammatory cells with immunohistochemistry in 21. We found different patterns of inflammation in ductal and lobular carcinoma. Diffuse inflammation was seen more in ductal carcinoma, particularly of high grade, and was predominantly composed of macrophages and T cells. It was associated with necrosis, but the correlation was weak, suggesting that other factors are important. Perilobular inflammation was seen most frequently in lobular and high-grade ductal carcinomas, particularly at the tumour edge. Perivascular inflammation was also largely at the tumour edge, but was not more common in any tumour type. In contrast to the diffuse inflammation, the perivascular and perilobular inflammation was composed of T and B cells. Normal lobules at the tumour edge showed consistent expression of HLA-DR, whereas lobules away from the tumour were negative. A combination of perilobular and perivascular inflammation composed of B and T cells with epithelial expression of HLA-DR mimicking lymphocytic lobulitis was seen more frequently in lobular than ductal carcinoma.

Adult↗
PubMed1996

Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients.

Immunohistochemical staining for oestrogen receptor (ER) has been carried out using antibody ER ID5 on 170 women who received first-line tamoxifen treatment for evaluable metastatic breast cancer. ER status had been determined some years previously, using a ligand-binding cytosol assay. The adequacy of the tissue used for the cytosol assay was always checked by histology on an adjacent block and was deemed to be typical of the tumour overall as was the block used for immunohistochemistry. Six different methods were used to assess the degree of staining and comparisons were made to determine which method gave the most clinically relevant results. Clinical outcome was assessed both in terms of duration of response to tamoxifen determined by log-rank analysis and type of response using the chi-squared test. The ER immunohistochemical assay gave superior results compared with the cytosol assay, with all of the subjective methods of assessment of staining giving statistically significant correlations with clinical outcome. The additional contribution of progesterone receptor (PR) staining with antibody NCL PGR was also studied.

Adult↗
PubMed1996

Sclerosing lymphocytic lobulitis in the male breast.

Sclerosing lymphocytic lobulitis is an inflammatory disorder of the breast that is well recognised in women. It has only been reported previously in two men; two further men with the condition are described here. Both presented with a breast mass, and one was an insulin dependent diabetic. Biopsy specimens from both patients showed circumscribed perivascular and, to a lesser extent, periductal collections of B and T lymphocytes. Sclerosing lymphocytic lobulitis in the female breast shows predominantly perilobular inflammation. The predominantly perivascular distribution in men is consistent with the relative paucity of epithelium in the male breast. Interlobular fibrosis with epithelioid fibroblasts was also present.

Biopsy↗
PubMed1995

Ductal carcinoma in situ: assessment of necrosis and nuclear morphology and their association with biological markers.

One hundred and five cases of pure ductal carcinoma in situ (DCIS) seen in the Guy's Hospital breast unit between 1975 and 1991 were reviewed. The presence and extent of necrosis and the degree of cytonuclear differentiation were assessed and the expression of p53 protein, cerbB2 protein, progesterone receptor, and a proliferation antigen KiS1, all factors reported to be of prognostic significance in invasive ductal carcinoma, was evaluated using immunohistochemical methods. A strong correlation was seen between the presence and extent of necrosis and the degree of cytonuclear differentiation and between both these morphological criteria and the biological markers as well as between the individual markers. The presence of extensive necrosis was associated with lack of cytonuclear differentiation and both were associated with a high proliferation rate, the presence of cerbB2 and p53 protein, and the absence of progesterone receptors. In cases with little or no necrosis, there was good nuclear differentiation and a strong correlation with the presence of progesterone receptor, absence of cerbB2 and p53 protein, and a low rate of proliferation.

Biomarkers, Tumor↗
PubMed1995

Cyclical tumour variations in premenopausal women with early breast cancer.

The hormonal milieu at the time of tumour excision may have a significant impact on survival in premenopausal patients with breast cancer, with those undergoing surgery between days 3 and 12 of the menstrual cycle having a worse prognosis. To investigate possible mechanisms which might explain this finding, histological features of tumours from 363 patients included in two studies from Guy's Hospital have been reviewed. Axillary nodal involvement occurred in 71/115 (62%) of patients whose primary tumour was excised between days 3 and 12 of the cycle, compared with 116/248 (47%) of patients undergoing surgery at other phases of the cycle (chi 2 = 7.04, P < 0.01). Vascular invasion was observed in 54/115 (47%) of primary tumours removed between days 3 and 12 and 82/248 (33%) of tumours removed at other times (chi 2 = 6.47, P < 0.02). Multivariate analysis of factors influencing survival indicated that both axillary nodal status and phase of the cycle were highly significant independent predictors of prognosis.

Breast Neoplasms↗
PubMed1995

The prognostic significance of DNA flow cytometry in breast cancer: results from 881 patients treated in a single centre.

In this single-centre study of 881 patients, S-phase fraction (SPF) was shown to be a significant prognostic marker in terms of overall survival (OS), relapse-free survival (RFS) and survival after relapse (SAR). Further, SPF had independent prognostic significance when considering a range of other clinicopathological variables, namely tumour grade and stage, nodal status, patient age, tumour size, menstrual status and treatment details. For OS and RFS, SPF was the second strongest predictor of the clinical course of the disease after nodal status, and for SAR it was the strongest prognostic marker. SPF correlated positively with histological grade but was the stronger predictor of survival. The distribution of SPF values was markedly different for the two ploidy classes of tumour, with DNA aneuploid tumours having a significantly higher average SPF. However, SPF retained its independent prognostic ability when DNA diploid and aneuploid tumours were analysed separately, DNA ploidy itself also proved to be an independent prognostic marker but the survival difference between the two ploidy classes was much less than that seen for different levels of SPF. Tumours with several DNA aneuploid populations (multiploid tumours) tended to have a worse prognosis than other aneuploid tumours but this trend did not reach statistical significance. In this and other studies from this centre, SPF has proved to be a robust predictor of clinical outcome in carcinoma of the breast.

Adult↗
PubMed1995

Carcinoma in situ involving sclerosing adenosis: a mimic of invasive breast carcinoma.

The distinction between invasive and in situ carcinoma of the breast is important with regard to the treatment and prognosis of the patient. When carcinoma in situ involves breast tissue in which the normal architecture is altered by pre-existing sclerosing adenosis, the resulting histological picture may closely mimic an invasive carcinoma. We record the histopathological features in 13 cases where there was difficulty in identifying the presence or extent of invasive carcinoma. The most useful clue was attention to the low power appearances of distorted lobular units in the areas of malignancy and comparison with surrounding breast tissue which usually showed recognizable sclerosing adenosis. The use of immunohistochemical stains for myoepithelium (alpha-actin and S-100 protein) and for basement membrane (collagen type IV and laminin) proved to be of considerable value in identifying the preservation of these features around glandular structures in areas of sclerosing adenosis containing in situ carcinoma.

Adult↗
PubMed1995

Metastatic breast carcinoma with appearance resembling micropapillary ductal carcinoma in situ.

AIM: To investigate tumour in an axillary lymph node resembling micropapillary ductal carcinoma in situ. METHODS: Sections of tumour in the breast and axillary lymph node were stained with haematoxylin and eosin, and immunohistochemically with antibodies to basement membrane and myoepithelial cells. RESULTS: Tumour in both the breast and axillary lymph node contained areas resembling micropapillary ductal carcinoma in situ. Surrounding these islands, there was a band of eosinophilic material resembling basement membrane and spindle cells that in places appeared to lie outside the basement membrane. Micropapillary tumour at both sites showed weak and discontinuous staining for collagen IV and laminin. The spindle cells stained for alpha-smooth muscle actin, but not for S100. By contrast, immunohistochemistry showed complete rings of basement membrane and myoepithelial cells around definite ductal carcinoma in situ and normal breast lobules and ducts. CONCLUSIONS: Invasive primary and metastatic carcinoma of the breast can have a growth pattern resembling micropapillary ductal carcinoma in situ.

Adenocarcinoma↗
PubMed1994

The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma.

The use of chemotherapy as a form of primary treatment for breast cancer is increasing and, as a result, more resection specimens contain tumours which have been exposed to cytotoxic drugs. We have studied the effects of chemotherapy on the tumour morphology and various biological features of breast carcinoma in a group of 35 patients. These were a group who responded to treatment in a clinical study of the use of primary chemotherapy designed to reduce tumour bulk prior to surgery. Characteristic morphological changes, temporally related to the administration of cytotoxic agents, are seen. The malignant cells become enlarged with vacuolated cytoplasm and vesicular nuclei containing prominent nuclei; occasionally the nuclei were angular and hyperchromatic. These features are interpreted as degenerative in nature. In 15 cases sufficient material was present in the pretreatment biopsies to compare the grade of the tumours before and after chemotherapy: changes were found in six tumours. Cytotoxic drugs do not induce a consistent pattern of change in the proliferation and apoptotic indices of individual tumours, but there is a tendency to reduce proliferative activity over all the tumours as a group. It was also found that chemotherapy is capable of modifying the expression of the oncoproteins c-erbB-2 and p53 in a minority of cases of breast cancer, usually resulting in an acquisition of immunoreactive oncoprotein. It is important to be aware of these effects when studying breast carcinomas removed after chemotherapy.

Adult↗
PubMed1994

Problems with p53 immunohistochemical staining: the effect of fixation and variation in the methods of evaluation.

The availability of antibodies which recognise p53 protein in paraffin-embedded tissue has created the opportunity to use immunohistochemistry to study the expression of p53 in a wide variety of clinical material. In this paper we have investigated the relationship between the type of fixative and the pattern of p53 staining in mammary carcinoma. Optimal results were obtained from breast tissue fixed in phenol formol saline, methacarn or cold formol saline with positive staining for stabilised p53 protein occurring in 69/95 (73%) cases studied. Care must be taken in the interpretation of these results since positive staining for p53 protein is not always indicative of mutation of the p53 gene. Furthermore, a range of staining patterns is seen in mammary carcinomas, making interpretation difficult. Assessment of staining needs to be standardised in order that different studies can be compared. However, in breast carcinoma, p53 immunohistochemistry appears to give information relating to tumour grade and, independently, to prognosis.

Breast Neoplasms↗
PubMed1994

Benign lymph node inclusions mimicking metastatic carcinoma.

AIMS: To draw attention to non-neoplastic inclusions in axillary lymph nodes removed from women with primary breast cancer which may be mistaken for metastases. METHODS: Five examples of non-malignant inclusions were detected in axillary lymph nodes removed from women with mammary carcinoma. Immunohistochemical staining for CAM 5.2 and S100 markers, as well as morphological assessment were performed. RESULTS: Three of the five cases comprised naevus cells and two heterotopic epithelial elements. One of each was initially mistaken for metastatic carcinoma. Naevus cells in the capsule of axillary nodes are often arranged as lines of small, round cells and may readily be misinterpreted as metastatic lobular carcinoma. Heterotopic epithelial elements, in the form of tubules, can easily be mistaken for metastasis from an infiltrating ductal carcinoma. CONCLUSIONS: Awareness of the occasional occurrence of non-neoplastic nodal inclusions will help avoid misdiagnosis. If immunohistochemical markers for epithelial cells are used to screen lymph nodes for metastasis, such lesions could be detected more frequently. It is important to combine immunohistochemistry with morphological assessment and the use of a panel of antibodies in histological diagnosis.

Adult↗
PubMed1994

Ductal carcinoma in situ: a proposal for a new classification.

Details of a proposed new classification for ductal carcinoma in situ (DCIS) are presented. This is based, primarily, on cytonuclear differentiation and, secondarily, on architectural differentiation (cellular polarisation). Three categories are defined. First is poorly differentiated DCIS composed of cells with very pleomorphic, irregularly spaced nuclei, with coarse, clumped chromatin, prominent nucleoli, and frequent mitoses. Architectural differentiation is absent or minimal. The growth pattern is solid or pseudo-cribriform and -micropapillary (without cellular polarisation). Necrosis is usually present. Calcification, when present, is amorphous. Second, at the other end of the spectrum is well-differentiated DCIS, composed of cells with monomorphic, regularly spaced nuclei containing fine chromatin, inconspicuous nucleoli, and few mitoses. The cells show pronounced polarisation with orientation of their apical border towards intercellular spaces usually resulting in cribriform, micropapillary and clinging patterns, although a solid pattern of well-differentiated DCIS also occurs. Necrosis is uncommon. Calcifications, when present, are usually psammomatous. The third category, intermediately differentiated DCIS, is composed of cells showing some pleomorphism but not so marked as in the poorly differentiated group. There is, however, always evidence of polarization around intercellular spaces, although this is not so pronounced as in the well-differentiated group. These two criteria, cytonuclear differentiation and architectural differentiation, have been found to be more consistent throughout a DCIS lesion than previously employed criteria of architectural pattern or the presence or absence of necrosis.

Breast Neoplasms↗