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R R Millis

Publications and source records attributed to R R Millis.

At least 55 records · Page 3Linked to original sources
PubMed1994

The classification of ductal carcinoma in situ and its association with biological markers.

One hundred five cases of pure ductal carcinoma in situ (DCIS) seen in the Guys Hospital breast unit between 1975 and 1991 were reviewed and reclassified using a modified histologic classification based on cytological features as well as histological architecture. 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 also evaluated using immunohistochemical methods. The mode of presentation of these cases was noted, and its relationship to biological markers and histologic type was also assessed. Good interobserver agreement was achieved by two independent observers using the modified histologic classification. Strong correlation was seen between histologic pattern and biological markers as well as between the individual markers. Poorly differentiated DCIS was associated with a high proliferation rate, the presence of cerbB2 and p53 protein and the absence of progesterone receptors. Well-differentiated DCIS showed the reverse, and the intermediate group showed an intermediate pattern. Paget's disease of the nipple was only seen in association with poorly differentiated DCIS, but no other significant association was noted between mode of presentation and DCIS type.

Adult↗
PubMed1994

Evaluation of infiltrating ductal carcinomas with a DCIS component: correlation of the histologic type of the in situ component with grade of the infiltrating component.

Recently there has been an increase in the detection of DCIS, and there is much interest in establishing a new pathologic classification that has less subjective criteria than traditional methods and that more closely reflects the clinical behavior of the tumor. It is hoped that this will lead to a more rational approach to treatment of DCIS. In this study one such recently proposed classification has been applied to the DCIS component of 215 infiltrating ductal carcinomas, and this has been compared with the histologic grade of the tumors. There was a highly significant correlation between DCIS type and grade (chi 2 = 110.0, P < 0.0001); well- and intermediately differentiated DCIS were usually found in grade I and grade II tumors, respectively. Poorly differentiated DCIS was equally associated with grade II and grade III infiltrating carcinomas. Furthermore, in univariate analysis, the DCIS type correlated with disease-free (chi 2 = 17.1, P < 0.001) and overall survival (chi 2 = 13.97, P < 0.001). In a Cox multivariate analysis, which included histologic grade, the association between DCIS type and prognosis was lost because of the very close relationship between type and grade. These results support the validity of the new classification and reinforce the view that treatment of pure DCIS should be related to tumor type.

Adult↗
PubMed1993

Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma.

Two members of the cadherin family of intercellular adhesion molecules are found in normal breast tissue: E-(epithelial) cadherin is present in both luminal and myoepithelial cells, whereas P- (placental) cadherin is confined to myoepithelium. There is experimental evidence that loss of E-cadherin is associated with increased invasiveness of malignant cells in vitro, which stimulated us to examine the presence and distribution of E- and P-cadherin in breast carcinomas by means of immunohistochemical staining. E-Cadherin was present in all in situ and invasive ductal carcinomas examined, although it had a patchy distribution and the staining was of variable intensity. However, in 83 per cent of invasive lobular carcinomas and all lobular carcinomas in situ there was complete loss of E-cadherin expression. In the remaining 17 per cent of invasive lobular tumours, E-cadherin appeared to have an abnormal distribution within the cytoplasm with variable expression on the cell membrane. P-Cadherin, by contrast, was absent from all benign breast luminal epithelium and 25 carcinomas of ductal and lobular type. It was found in only one carcinoma of lobular type. We suggest that loss of cell-cell adhesion mediated by E-cadherin plays a part in the characteristic morphology of lobular carcinomas.

Breast Neoplasms↗
PubMed1993

Breast lymphomas: a clinicopathologic review.

Primary lymphoma is an uncommon tumor in the breast. Review of the literature shows two distinct clinicopathologic groups. One, which affects young women, is frequently bilateral, is often associated with pregnancy, and is a Burkitt-type lymphoma. The second group affects older women, is usually B-cell non-Hodgkins-type lymphoma, and presents clinical features identical to carcinoma of the breast. Three recent studies have suggested that up to half of the cases in the latter group belong to the category of lymphomas arising from the mucosa-associated lymphoid tissues. We have identified nine cases of primary lymphoma from the files of Guys Hospital Clinical Oncology Breast Unit in the 16-year period from 1974 to 1990. The clinical features have been reviewed and the tumors have been evaluated both on a morphologic and an immunohistochemical basis, and seven of nine of the cases have been screened for t[14;18] translocation using the polymerase chain reaction. All the tumors occurred in women older than 50 years and who presented with features of mammary carcinoma. One tumor was true histiocytic lymphoma; the remaining eight cases were B-cell lymphomas. Seven of the latter cases were high-grade B-cell lymphomas and one was a true follicular lymphoma. None of our cases showed the features of lymphoma arising in mucosa-associated lymphoid tissue.

Aged↗
PubMed1993

Immunohistochemical detection of p53 protein in mammary carcinoma: an important new independent indicator of prognosis?

In an immunohistochemical pilot study of 195 primary breast cancer patients with a 10-year median follow-up we found that patients with carcinomas who express p53 protein in the majority of their tumor cells (19% of the cases) have a considerably worse prognosis than those who do not. The effect of the presence of the protein is seen on disease-free interval (chi-square, 11.69; P < .001), overall survival (chi-square, 19.68; P < .001), and survival after relapse (chi-square, 4.93; P < .02), and is seen in node-negative (chi-square, 6.99; P < .009) and node-positive (chi-square, 13.05; P < .001) patients. Furthermore, the effect is most apparent in patients with infiltrating lobular and grade II infiltrating ductal carcinomas (chi-square, 27.97; P < .001) that have a rather heterogeneous clinical behaviour and are difficult to subdivide on the basis of currently available markers. Cox multivariate analysis shows that p53 majority staining is second only to node status in significance of effect on overall survival.

Adult↗
PubMed1993

Patterns of metastatic breast cancer in relation to histological type.

We have examined the clinical records fo 1238 patients with operable breast cancer to identify the sites of metastatic disease. Infiltrating ductal carcinoma (IDC) recurred more commonly in lung (P < 0.05), pleura (P < 0.05) and brain (P < 0.05), while infiltrating lobular carcinoma (ILC) more commonly metastasised to the bone marrow (P < 0.01) and peritoneum (P < 0.01). Bone involvement as the initial presentation of distant metastatic disease occurred in over 50% of women with ILC, significantly more commonly than in those with IDC (34%, P < 0.01). Survival was similar for the two groups, both from time of diagnosis and from time of development of distant metastases.

Adult↗
PubMed1993

Immunochemical analysis of the p53 oncoprotein in matched primary and metastatic human tumours.

There is much interest in the range of genetic aberrations which occur in human malignancies. An immunohistochemical study has been carried out to investigate the consistency of expression of abnormally accumulated p53 protein in paired samples of archival primary and metastatic carcinomas. The staining of methacarn-fixed tissue from 136 matched pairs of mammary carcinoma and 20 cancers from other sites was completed using antibody CM-1 and DO1 in a sensitive peroxidase-conjugated streptavidin-biotin technique. The majority of tumour cells were positive in 25% and the tumours were negative in 17% of the primary carcinomas; staining was heterogeneous in the remaining cases. Staining was identical in 180/186 (96%) metastatic lesions. An ELISA assay carried out on 12 matched pairs of the tumour specimens demonstrated that altered conformation of the aberrant p53 protein present in a primary lesion was maintained in its metastasis. These data indicate that alterations in the p53 gene result in a relatively stable phenotype and that progression of disease is not usually accompanied by either further mutation or loss of the mutant allele.

Breast Neoplasms↗
PubMed1993

Microglandular adenosis, apocrine adenosis, and tubular carcinoma of the breast. An immunohistochemical comparison.

Four cases of microglandular adenosis (MA), together with four cases of apocrine adenosis (AA) and 10 cases of tubular carcinoma (TC) of the breast were studied at the light and immunohistochemical level. One case of MA was studied with electron microscopy. MA is characterized by an absence of myoepithelial cells (ME), epithelial membrane antigen (EMA), and gross cystic disease fluid protein (GCDFP-15). The absence of EMA in MA makes it unique among benign glandular hyperplasias of the breast. AA contains myoepithelial cells and a distinct basal lamina. It is characterized by the presence of GCDFP-15, the specific apocrine marker, which is not present in MA. TC lacks both myoepithelial cells and a basal lamina. It is negative for GCDFP-15. Periductal and vascular elastosis are common and usually prominent, whereas they are not found in either MA and AA. Other stromal changes further distinguish the three lesions. These three distinct entities can be separated objectively and unequivocally and it is essential that this be done so as to prevent confusion.

Actins↗
PubMed1993

Oestrogen and progesterone receptor expression in mammary fibromatosis.

AIMS: To investigate the oestrogen and progesterone receptor concentrations expressed on mammary fibromatoses to determine their responsiveness to oestrogenic stimuli. METHODS: Six mammary fibromatoses were examined using immunohistochemistry for the presence of oestrogen and progesterone receptors using antibodies against the receptor proteins. Enzyme immunoassays (EIAs) using the same antibodies were also performed in four patients. Immunohistochemical staining for pS2 protein was also carried out as a measure of functional oestrogen receptors. RESULTS: Neither receptor nor pS2 protein was expressed using immunohistochemistry. Very low concentrations of both oestrogen and progesterone receptors were shown by EIA. CONCLUSION: These results indicate the absence of clinically important concentrations of oestrogen and progesterone receptors in breast fibromatoses and suggest that treatment directed against oestrogen is unlikely to be beneficial.

Adult↗
PubMed1992

Overexpression of the c-erbB-2 oncoprotein: why does this occur more frequently in ductal carcinoma in situ than in invasive mammary carcinoma and is this of prognostic significance?

Overexpression of c-erbB-2 occurs in 60% of in situ and 25% of infiltrating ductal carcinomas. We have previously found very strong associations between immunohistochemical staining for c-erbB-2 and histological pattern and nuclear size in ductal carcinoma in situ (DCIS) and less strong correlation with proliferative activity. In a further study of infiltrating ductal carcinomas we have found that, in addition to tumours arising from c-erbB-2 positive, large celled, rapidly proliferating, comedo carcinomas and c-erbB-2 negative small celled cribriform/micropapillary carcinomas with a low proliferative rate, there is a third group of c-erbB-2 negative tumours with large nuclei and variable proliferative activity. These latter tumours are not seen in pure DCIS suggesting that they have a very transient in situ stage. Therefore, although in pure DCIS c-erbB-2 positively appears to be associated with tumours with a greater invasive potential, and c-erbB-2 negativity with tumours having a more favourable prognosis, the latter is not necessarily true in infiltrating disease.

Breast Neoplasms↗
PubMed1992

Relationship of blood prolactin levels and the risk of subsequent breast cancer.

Between 1968 and 1976 a total of 5162 women volunteers were enrolled into a prospective study conducted on the Island of Guernsey. Up to February 1990 145 women subsequently developed breast cancer. Blood samples were taken at the time of enrollment and prolactin levels were known for 85% of the volunteers. In calculating the relationship between blood prolactin levels and subsequent breast cancer risk, women were excluded if they had a hysterectomy or an oophorectomy or had cancer at any site before enrollment. The final analysis was based on 2596 premenopausal and 1180 naturally postmenopausal women and, of these respectively, there were 71 and 40 volunteers who subsequently developed breast cancer. The total follow-up for these two groups was 49,941 and 22,360 woman-years, respectively. In assessing the relationship between blood prolactin levels and risk of subsequent breast cancer the cohort was divided into quintiles according to prolactin concentration and relative risks (RR) were estimated. In calculating these values possible confounding by age at entry, age at menarche, parity, age at first birth, years since menopause, body build, history of benign breast disease and family history of breast cancer were taken into consideration. There was no significant relation between risk of breast cancer and prolactin in either pre- or postmenopausal women. Hence prolactin appears not to be an important determinant of breast cancer risk.

Adolescent↗
PubMed1992

Mammary hamartoma--a review of 35 cases.

Mammary hamartomas are macroscopically well-delineated tumours composed of a variable mixture of epithelial elements, fat and fibrous tissue. Such lesions are an under-recognized entity and, as they can be visualized by mammography, may be seen more frequently with the advent of the UK National Breast Screening Programme. The clinical and pathological features of 35 cases of mammary hamartoma seen at the Imperial Cancer Research Fund Clinical Oncology Unit at Guy's Hospital between 1979 and 1990 have been reviewed. Hormone receptor analysis on nine cases gave high progesterone with low oestrogen levels, probably reflecting their premenopausal status. Immunohistochemistry showed that the positive receptor staining was confined to the epithelial elements. In 25 cases pseudo-angiomatous hyperplasia was evident in the stroma of the lesion. The importance of distinguishing the inter-anastomosing stromal spaces seen in the latter condition from low-grade angiosarcoma is emphasized; the relationship between pseudo-angiomatous hyperplasia and mammary hamartoma is discussed; and the possibility that the former represents a permanently dilated form of the lymphatic labyrinth suggested.

Adolescent↗
PubMed1992

Phyllodes tumours: a clinicopathological review of 30 cases.

Thirty cases of phyllodes tumour (cystosarcoma phyllodes) of the breast that presented to the Clinical Oncology Unit at Guy's Hospital were reviewed. Tumours were classified as benign, malignant or borderline according to the following histological criteria: mitotic rate, nuclear pleomorphism, stromal overgrowth and tumour margins. In 14 (46.5%) cases the tumours were considered histologically benign, in 11 (36.5%) malignant, and in five (17%) borderline. Recurrence was seen in a similar proportion of patients with tumours classified as benign (21%) and malignant (18%) according to histological criteria. Malignant lesions tended to recur earlier. Infiltrating tumour margins were noted in all patients and stromal overgrowth in all but one in whom recurrence was observed. Risk of recurrence also appeared to be related to tumour size. Only one patient developed distant metastases and died of her disease. Because of treatment variation no conclusion can be made regarding optimal therapy but the importance of adequate clearance, either through wide excision or mastectomy, is emphasized for all phyllodes tumours irrespective of histological features.

Adult↗
PubMed1991

Relationship between c-erbB-2 immunoreactivity and thymidine labelling index in breast carcinoma in situ.

The relationship between the presence of the c-erbB-2 protein, demonstrated immunohistochemically with antibody 21N, and thymidine labelling index (TLI) has been studied in the in situ component of 70 cases of carcinoma of the breast. A significant association was found between high TLI and positive staining. Twenty of the 70 cases stained (29%) and of those that were stained 75% had a high TLI; 43% of those with a high TLI stained positively but only 14% of those with a low TLI stained positively. Strong correlations were seen between nuclear size and histological pattern and both 21N staining and TLI. The majority of carcinomas of comedo pattern with large nuclei were 21N positive and had a high TLI, whilst those with small nuclei and a predominantly cribriform/micropapillary appearance did not stain and had a low TLI. In tumours of mixed histological pattern there was less concordance between staining and TLI. The significance of these findings in relation to the biological behaviour of these tumours and their clinical management is discussed.

Breast Neoplasms↗
PubMed1991

Breast cancer in English and Japanese women: prognostic significance of sinus histiocytosis and germinal center hyperplasia in axillary lymph nodes.

A prospective study of comparable Japanese and British breast cancer patients treated by radical mastectomy confirmed previously reported findings that sinus histiocytosis and germinal center hyperplasia are more frequently seen in axillary lymph nodes from Japanese than in those from British patients. In Japanese, but not British, cases of either of these two morphologic findings had favorable prognostic significance for recurrence. Sinus histiocytosis also had favorable prognostic significance in Japanese cases for five year survival. In a separate review of axillary nodes from Japanese autopsy cases sinus histiocytosis was absent, suggesting that this finding in Japanese breast cancer cases was related to presence of the disease.

Breast Neoplasms↗