Search PubMed⌕ Search

Biomedical subjects

C W Elston

Publications and source records attributed to C W Elston.

At least 91 records · Page 5Linked to original sources
PubMed1994

Screening-detected and symptomatic ductal carcinoma in situ: mammographic features with pathologic correlation.

PURPOSE: To compare the mammographic and pathologic features of screening-detected and symptomatic ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: The mammographic and pathologic features of 54 screening-detected and 77 symptomatic cases of DCIS were compared. Patients were aged 30-76 years (mean, 58 years). RESULTS: Diffuse involvement was seen in 10 patients (13%) with symptoms but in none of the screening-detected group (P < .05). The disease was radiologically more extensive in the symptomatic group. Calcifications in the symptomatic group (n = 48) were less likely to have a ductal distribution than those in the screening-detected group (n = 48) (30 [63%] vs 40 [83%], respectively; P < .05). At histologic examination in some cases, the symptomatic group (n = 76) included eight (11%) patients with cribriform-micropapillary, large-cell tumors (P < .05) and less comedocarcinoma (20 [26%] vs 23 [45%], respectively; P < .05) compared with the screening-detected group (n = 51). CONCLUSION: The results show differences in the radiologic and pathologic features of screening-detected and symptomatic DCIS.

Adult↗
PubMed1994

Ideas in pathology. Ductal carcinoma in situ of the breast: a proposal for a new simplified histological classification association between cellular proliferation and c-erbB-2 protein expression.

UNLABELLED: The diagnosis of ductal carcinoma in situ of the breast (DCIS) has become common with the advent of breast screening programs. METHODS: Proliferation indices (S-phase fraction) were studied in 76 cases of pure DCIS. Tumors were classified according to conventional criteria and also according to a novel simplified classification based on cellular necrosis and morphology. This new classification defines three distinct tumor groups: pure comedo in 19 (25.0%) cases, DCIS with necrosis (non-pure comedo) in 21 (27.6%) patients, and DCIS without necrosis in 36 (47.4%) of cases, the latter group comprising largely classical cribriform or micropapillary architectural subtypes. RESULTS: Flow cytometric DNA analysis showed a significantly higher S-phase fraction in comedo DCIS than in the subgroup of DCIS tumors without necrosis (P < 0.01 [anova]). A preliminary analysis of disease recurrence and disease-free survival in a large series of 391 cases of pure DCIS showed that of 181 cases of pure comedo DCIS there were 19 local recurrences at the 7-year stage (82% 7-year disease-free survival), with 5 local recurrences in 51 cases of DCIS with necrosis (non-pure comedo) (85% 7-year disease-free survival) and only 6 local recurrences in the 159 cases of the DCIS-without-necrosis subgroup (94% 7-year disease-free survival). The chi 2 value for the frequency of disease recurrence of all cases of DCIS with necrosis (i.e., combining the groups of comedo DCIS and DCIS with necrosis (non-pure comedo)) as compared to DCIS without histological evidence of necrosis was 5705 (df = 2; P = 0.0001), and the chi 2 for disease-free survival of types of DCIS with necrosis as compared to cases without necrosis was 178 (df = 2; P = 0.0001). This analysis indicates that the histological presence of necrosis appears to be a relatively powerful predictor of increased disease recurrence and poorer disease-free survival after treatment for DCIS. CONCLUSIONS: Necrosis in DCIS in the absence of pure classical comedo morphology is a feature of more biologically aggressive in situ breast cancer with an intermediate proliferative fraction as compared with the high proliferative fraction of pure comedo DCIS and the low proliferative fraction of DCIS without necrosis. There was no significant difference in DNA ploidy (diploid or aneuploid) between the subgroups as assessed by chi 2 analysis. Further larger studies are required to establish if DCIS with necrosis (non-pure comedo) also shows a greater tendency to local recurrence after breast conservation treatment than do subtypes of DCIS without necrosis. DCIS with necrosis (non-pure comedo) should be adopted as a distinct histological subgroup of DCIS in future clinical studies of in situ mammary carcinoma.

Biomarkers, Tumor↗
PubMed1993

p53 protein expression in mammary ductal carcinoma in situ: relationship to immunohistochemical expression of estrogen receptor and c-erbB-2 protein.

The immunohistochemical expression of the p53 gene protein was examined in a consecutive series of 143 cases of pure ductal carcinoma in situ (DCIS) of the breast. Expression of wild-type and/or mutant p53 protein was detected in 36 (25.2%) of the cases examined, as evidenced by positive nuclear staining with the monoclonal antibody DO 7. Thirty-four (35.8%) of the large cell cases showed p53 protein expression compared with two (4.1%) of the small cell cases (chi 2 = 15.3 [df = 1], P < .001). p53 Protein expression also was associated with an increased histologic degree of necrosis, with a nearly significant association of negative tumor estrogen receptor status and p53 protein expression. No significant association of p53 protein expression and c-erbB-2 protein expression was seen. Immunohistochemical expression of p53 protein is present in approximately 25% of DCIS cases and is confined almost exclusively to large cell DCIS, a morphologic subtype of in situ breast carcinoma thought to be more biologically aggressive. Expression of p53 protein may be important in the neoplastic progression of DCIS, reflecting the acquisition of p53 gene mutations in large cell DCIS cases. Therefore, p53 may be implicated in mammary tumor evolution from in situ to invasive disease.

Biomarkers, Tumor↗
PubMed1993

Oestrogen receptor expression in ductal carcinoma in situ of the breast: relationship to flow cytometric analysis of DNA and expression of the c-erbB-2 oncoprotein.

The expression of oestrogen receptor protein (ER) was examined in 151 cases of symptomatic or screening detected pure ductal carcinoma in situ (DCIS) of the breast by immunocytochemical assay (ERICA), in formalin-fixed paraffin-embedded tissue, with the monoclonal antibody H 222 (Abbott). Forty-eight tumours (31.8%) of cases were ER positive. Twenty-seven (17.9%) of cases showed high level ER expression and 21 (13.9%) of cases showed low level ER immunoreactivity. Significant associations of positive tumour ER immunoreactivity and non-comedo architecture chi 2 = 6.76; (d.f. = 1): P < 0.001, small cell size chi 2 = 4.49; (d.f. = 1): P = 0.034, higher S-phase fraction chi 2 = 4.71; (d.f. = 1): P = 0.03 and lack of c-erbB-2 protein overexpression chi 2 = 7.96; (d.f. = 1): P < 0.01 were identified. No significant associations of ER expression and patient age, histological grade of necrosis in DCIS, or DNA ploidy were found. ER expression is detectable in less than one third of symptomatic and screening detected cases of DCIS, implying that endocrine therapy of DCIS may be a more appropriate form of management for morphological subtypes of DCIS which show higher rates of oestrogen receptor expression, particularly those of non-comedo and small cell type.

Adult↗
PubMed1993

Methodology of immunohistological detection of oestrogen receptor in human breast carcinoma in formalin-fixed, paraffin-embedded tissue: a comparison with frozen section methodology.

We describe a method of immunohistochemically assessing estrogen receptor status on routinely processed formalin-fixed tissue, using a commercially available monoclonal antibody (Abbott H222), with pronase predigestion of tissue sections and overnight antibody incubation. The staining was assessed using the H score system. A series of 94 cases of breast cancer were analysed and the results were compared with assessment by oestrogen receptor immunocytochemical assay performed on frozen section. Direct comparison of the paired sets of H scores obtained with frozen tissue and formalin-fixed tissue showed a highly significant correlation of 0.8 (P < 0.001) between the two methods of oestrogen receptor assessment. Chi-squared analysis using H score cut off points of 50 and 100 also showed a similar significant association (P < 0.001). We conclude that this oestrogen receptor method, applicable to formalin-fixed, paraffin-embedded tissue, gives accurate results on routinely fixed tissue and could be used as an alternative to other methods.

Adenocarcinoma↗
PubMed1993

Expression of tumour-associated antigens in breast cancer primary tissue compared with serum levels.

The level of expression of six breast cancer-associated antigens or markers (CEA, NCRC-11, HMFG1, HMFG2, D8 and DF3) in primary tumour tissue and patients' serum has been compared. Two-hundred-and-forty-five consecutive patients with newly-diagnosed breast cancer had tumour biopsy and serum samples taken prior to any anti-cancer therapy (Stage I and II disease n = 100, Stage III disease n = 60, Stage IV disease n = 85). No correlations were found between the level of tumour tissue staining and serum levels of the same antigens. Those samples from patients with Stage IV disease were also analysed separately but again no correlations were observed. Therefore the staining pattern of the primary tumour for these antigens is not a predictor of which tumour marker will be elevated in the serum.

Antibodies, Monoclonal↗
PubMed1992

Tumour oestrogen receptor content allows selection of elderly patients with breast cancer for conservative tamoxifen treatment.

Immunocytochemical analysis was used to determine tumour oestrogen receptor (ER) content in elderly patients with primary operable breast cancer. Only those ER positive were selected for conservative treatment with tamoxifen alone. Initial response was compared with that of historical controls not selected according to ER status. Early progressive disease was markedly reduced at 6 months, from 30 per cent in the unselected control group to 2 per cent in the study group (P < 0.001). Immunocytochemical analysis is useful for the initial selection of elderly patients with breast cancer who may be treated with tamoxifen alone.

Aged↗
PubMed1992

Confirmation of a prognostic index for patients with metastatic breast cancer treated by endocrine therapy.

We have previously reported a retrospectively constructed index which can accurately predict survival at the time of diagnosis of symptomatic metastatic breast cancer. The index, derived from a Cox model, is scored: Index score = (4 x Grade)-(6 x ER) + (4 x SIMD)-(0.1 x DFI), where histological grade is scored 1-3 (good, moderate, or poor), oestrogen receptor (ER) is scored 0 (negative) or 1 (positive), site of initial metastasis (SIMD) is scored 1-4 for bone only, lung only, bone and lung, or visceral metastases, respectively, and disease-free interval (DFI) is measured in months. Patients were divided into three prognostic groups on the basis of index score. In the present study we have tested this index prospectively on a new group of 147 patients with metastatic breast cancer. The percentage of patients in each of the three groups was similar between the retrospective and prospective studies. In the prospective study the difference in survival between the 3 groups was highly significant (p less than 0.001), confirming our retrospective analysis. No single one of the four factors was as powerful in predicting survival as the index itself. We now use this index in our patient management.

Adult↗
PubMed1992

Mastectomy or tamoxifen as initial therapy for operable breast cancer in elderly patients: 5-year follow-up.

135 consecutive patients aged over 70 years with operable primary breast cancer (clinically maximum diameter 5 cm) were randomised to either wedge mastectomy or tamoxifen 20 mg twice daily as initial therapy. The mean time from randomisation is now 65 months. There was no difference between the two groups in terms of overall survival or cause of death. Likewise, the groups were similar for site of initial metastatic disease and the probability of developing metastatic disease. However, failure of locoregional control was significantly greater in the tamoxifen group. The optimum treatment for elderly patients with operable breast cancer includes mastectomy.

Aged↗
PubMed1992

P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy.

Using immunohistochemistry and the monoclonal antibody C219 we have investigated P-glycoprotein expression in 26 locally advanced breast cancers. Twenty four patients had received four cycles of chemotherapy (mitozantrone, mitomycin-C and methotrexate) prior to mastectomy; two received tamoxifen. Twelve tumours exhibited an objective response to the chemotherapy. A background pattern of isolated weakly positive (1+) stromal staining (myofibroblast) was observed in seven tumours, two of which had been treated by tamoxifen alone. Two of the tumours treated by induction chemotherapy showed positive staining (1+) within a very small number of isolated tumour cells (maximum of three) and macrophages. The significance of this staining is not clear although C219 may simply be cross reacting with myosin. We have failed to demonstrate a clear clinical utility for C219 in breast cancer, particularly regarding the identification of patients in whom MDR chemotherapy be avoided once metastases develop.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

p53 protein expression in human breast carcinoma: relationship to expression of epidermal growth factor receptor, c-erbB-2 protein overexpression, and oestrogen receptor.

The expression of p53 protein, oestrogen receptor protein, epidermal growth factor receptor (EGFR) and overexpression of the c-erbB-2 oncoprotein was examined in a series of 149 primary symptomatic breast carcinomas. Expression of p53 was present in 62 of 146 cases (42.5%) of the invasive carcinoma and one of three cases (33.3%) of ductal carcinoma in situ (DCIS) examined. Statistical associations of tumour oestrogen receptor positivity and lack of p53 protein expression, chi 2 = 19.78 (d.f. = 1), P less than 0.001, positive tumour p53 status and poor tumour grade; chi 2 = 14.1 (d.f. = 2), P less than 0.001, EGFR expression chi 2 = 7.07, (d.f. = 1), P less than 0.01 and tumour c-erbB-2 protein overexpression; chi 2 = 4.61 (d.f. = 1), P = 0.032 were identified. Expression of p53 is rare in invasive lobular carcinoma of classical type (8.3% of cases examined) in contrast to other common types of mammary carcinoma. Non-significant trends of p53 protein expression and increased regional tumour recurrence; chi 2 = 3.20 (d.f. = 1), P = 0.074 and also poorer patient survival; chi 2 = 3.76 (d.f. = 1), P = 0.053 were identified. p53 protein expression is a common event in human breast cancer and is present in both DCIS and invasive mammary carcinoma. Abnormal expression of p53 protein is a feature of both in situ and invasive breast carcinoma, implying that the abnormal p53 protein expression may be implicated in the early stages of mammary carcinoma progression.

Biomarkers, Tumor↗
PubMed1992

Routine diagnosis of mammary Paget's disease. A modern approach.

This study compares the diagnostic reliability of conventional mucin histochemistry and immunocytochemical techniques in distinguishing mammary Paget's disease from superficial spreading malignant melanoma and primary intraepidermal carcinoma. Formalin-fixed, paraffin-embedded archival tissue was used and comprised 13 cases of mammary Paget's disease, five cases of superficial spreading melanoma, and six cases of intraepidermal carcinoma. Sections from each case were stained for the presence of mucin using diastase periodic-acid-Schiff (d-PAS) with and without an alcian blue counterstain as well as immunocytochemistry for cytokeratin (CAM 5.2), epithelial membrane antigen (NCRC-11) and c-erb B-2 (21N). Mucin staining in intraepidermal carcinoma and malignant melanoma was consistently negative. Diastase-resistant PAS positivity was seen in six of 13 cases of mammary Paget's disease and eight of 13 cases using an alcian blue counterstain. NCRC-11 showed positive immunoreactivity in four of six cases of intraepidermal carcinoma, one in five cases of melanoma, and five of 13 cases of mammary Paget's disease. Positive immunoreactivity using CAM 5.2 and 21N was seen in all cases of mammary Paget's disease, with consistent negative immunoreactivity in the other tumor types. We conclude that CAM 5.2 and 21N should be used in the investigation of mammary Paget's disease in preference to conventional mucin stains.

Antibodies, Monoclonal↗
PubMed1992

Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up.

The histological tumour type determined by current criteria has been investigated in a consecutive series of 1621 women with primary operable breast carcinoma, presenting between 1973 and 1987. All women underwent definitive surgery with node biopsy and none received adjuvant systemic therapy. Special types, tubular, invasive cribriform and mucinous, with a very favourable prognosis can be identified. A common type of tumour recognized by our group and designated tubular mixed carcinoma is shown to be prognostically distinct from carcinomas of no special type; it has a characteristic histological appearance and is the third most common type in this series. Analysis of subtypes of lobular carcinoma confirms differing prognoses. The classical, tubulo-lobular and lobular mixed types are associated with a better prognosis than carcinomas of no special type; this is not so for the solid variant. Tubulo-lobular carcinoma in particular has an extremely good prognosis similar to tumours included in the 'special type' category above. Neither medullary carcinoma nor atypical medullary carcinoma are found to carry a survival advantage over carcinomas of no special type. The results confirm that histological typing of human breast carcinoma can provide useful prognostic information.

Breast Neoplasms↗
PubMed1992

Ki67 immunoreactivity in breast carcinoma: relationships to prognostic variables and short term survival.

Immunoreactivity of the monoclonal antibody Ki67, which recognizes an antigen expressed in cells active in the cell cycle, has been investigated by immunocytochemistry in a series of 67 primary breast cancers. The percentage of tumour cell nuclei stained by Ki67 (labelling index) was related to tumour histological grade, mitotic frequency, oestrogen receptor status and tumour type. No correlation was found with patient age, tumour size or lymph node stage. A high Ki67 labelling index was significantly associated with diminished patient survival and disease-free interval, which demonstrates an important role for this monoclonal antibody as a prognostic marker in breast cancer.

Antibodies, Monoclonal↗
PubMed1991

Paget's disease of the nipple.

A total of 48 women with Paget's disease of the nipple (nipple eczema containing Paget cells but without a palpable lump) presented to one surgeon over a 13-year period. Temporary healing of the nipple eczema occurred in six patients. In all, 21 of 34 patients with in situ (DCIS) or invasive ductal carcinoma had mammographic abnormalities. Treatment was by simple mastectomy (37 cases), cone excision of the nipple-areola complex (ten cases) and tamoxifen (one case). DCIS was found in 45 operative specimens (96 per cent); eight had associated invasion. The DCIS was predominantly large cell solid/comedo in type and was multifocal in seven cases (19 per cent). At a median (range) follow-up of 56 (18-96) months, four of the ten patients treated by cone excision have developed a local recurrence, two of these patients have also developed metastases. Two of the 37 patients who underwent mastectomy developed loco-regional recurrences; both had invasive foci at their first operation and remain disease free at 8 years. We no longer feel that cone excision is appropriate treatment.

Adult↗
PubMed1991

Occult regional lymph node metastases from breast carcinoma: immunohistological detection with antibodies CAM 5.2 and NCRC-11.

Ninety-eight consecutive patients with primary operable breast cancer and an initial diagnosis of no regional lymph node metastases as assessed by conventional light microscopy were studied. Immunohistological staining of routine lymph node sections was assessed using two monoclonal antibodies: CAM 5.2 (Becton Dickinson) with specificity for low molecular weight cytokeratin, and NCRC-11 (CRC Laboratories, Nottingham) with specificity for epithelial mucin antigen. Positive staining for occult metastases was seen in nine patients with CAM 5.2 and in eight of these nine with NCRC-11. At a follow-up out to 14 years, there was no difference in overall survival, in recurrence-free survival, or in frequency of or time to presentation of local or regional recurrences between occult metastasis-positive and occult metastasis-negative patients. This study concludes that while immunohistological staining of routine lymph node sections increases the diagnostic yield of metastases, it is not to be recommended as this increase is of no useful clinical value.

Adenocarcinoma↗