Biomedical subjects

Sami Shousha

Publications and source records attributed to Sami Shousha.

11 recordsLinked to original sources

PubMed2005

Quantification of cellular proliferation in tumor and normal tissues of patients with breast cancer by [18F]fluorothymidine-positron emission tomography imaging: evaluation of analytical methods.

There is an unmet need to develop imaging methods for the early and objective assessment of breast tumors to therapy. 3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT)-positron emission tomography represents a new approach to imaging thymidine kinase activity, and hence, cellular proliferation. We compared graphical, spectral, and semiquantitative analytic methodologies for quantifying [18F]FLT kinetics in tumor and normal tissue of patients with locally advanced and metastatic breast cancer. The resultant kinetic parameters were correlated with the Ki-67 labeling index from tumor biopsies. [18F]FLT accumulation was detected in primary tumor, nodal disease, and lung metastasis. In large tumors, there was substantial heterogeneity in regional radiotracer uptake, reflecting heterogeneity in cellular proliferation; radiotracer uptake in primary tumors also differed from that of metastases. [18F]FLT was metabolized in patients to a single metabolite [18F]FLT-glucuronide. Unmetabolized [18F]FLT accounted for 71.54 +/- 1.50% of plasma radioactivity by 90 minutes. The rate constant for the metabolite-corrected net irreversible uptake of [18F]FLT (Ki) ranged from 0.6 to 10.4 x 10(-4) and from 0 to 0.6 x 10(-4) mL plasma cleared/s/mL tissue in tumor (29 regions, 15 patients) and normal tissues, respectively. Tumor Ki and fractional retention of radiotracer determined by spectral analysis correlated with Ki-67 labeling index (r = 0.92, P < 0.0001 and r = 0.92, P < 0.0001, respectively). These correlations were superior to those determined by semiquantitative methods. We conclude that [18F]FLT-positron emission tomography is a promising clinical tool for imaging cellular proliferation in breast cancer, and is most predictive when analyzed by graphical and spectral methods.

Breast Neoplasms↗

PubMed2005

Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial.

BACKGROUND: Some oestrogen-receptor (ER) positive breast cancers express epidermal growth factor receptor (EGFR), but whether inhibition of EGFR can suppress proliferation of breast cancer cells and ER function is not known. METHODS: In a double-blind, placebo-controlled randomised trial of 56 postmenopausal patients with ER-positive and EGFR-positive primary breast cancer, 27 women were randomly assigned to the tyrosine-kinase inhibitor of EGFR gefitinib (250 mg given orally once a day) and the aromatase inhibitor anastrozole (1 mg given orally once a day), and 29 women to gefitinib (250 mg given orally once a day) and placebo of identical appearance to anastrozole given orally once a day, all given for 4-6 weeks before surgery. Primary outcome was inhibition of tumour-cell proliferation, as measured by Ki67 antigen labelling index. Secondary outcomes were reduction in EGFR phosphorylation at Tyr 845, reduction in ER phosphorylation at Ser 118, tumour size, and toxic effects. Analyses were by intention to treat. FINDINGS: Patients assigned gefitinib and anastrozole had a greater reduction from pretreatment values in proliferation-related Ki67 labelling index than did those assigned gefitinib alone (mean % reduction 98.0 [95% CI 96.1-98.9] vs 92.4 [85.1-96.1]; difference between groups 5.6% [5.1-6.0], p=0.0054). Tumour size was reduced by 30-99% (partial response) in 14 of 28 patients assigned gefitinib and [corrected]in 12 of 22 assigned gefitinib, as assessed by ultrasonography. Reduction in phosphorylation of ER at Ser 118 was similar for both groups. Treatment was well tolerated and much the same for both groups. INTERPRETATION: Single-agent gefitinib and gefitinib combined with anastrozole are well-tolerated and effective treatments for reducing the size of breast tumours and levels of ER phosphorylation when given as neoadjuvant therapy.

Anastrozole↗

PubMed2004

Invasive ductal carcinoma of the breast with large central acellular zones (ring carcinoma): imaging and clinical findings in eight cases.

OBJECTIVE: To review the mammographic and ultrasound appearances in patients who have invasive ductal carcinoma with a central acellular zone (ring carcinoma), as this feature has been reported to be associated with a poorer outcome. MATERIALS: Eight patients were identified with ring carcinomas. Two breast radiologists reviewed their mammograms and ultrasound images. Patient records were reviewed to assess outcome. RESULTS: All patients had lesions deep within the breast, adjacent to the chest wall, five lesions were incompletely visualised on mammography. The appearance was of a circumscribed or obscured mass, without microcalcification. Five patients had ultrasound demonstrating a solid well-circumscribed hypoechoic microlobulated lesion. CONCLUSION: In our series of patients who have a ring carcinoma of the breast, mammographic and ultrasound appearances were similar in all cases and lacked the typical features of malignancy.

Aged↗

PubMed2004

The expression of ER beta cx in human breast cancer and the relationship to endocrine therapy and survival.

PURPOSE: Estrogen receptor (ER) alpha-positive breast cancer is often treated with endocrine therapy using either antiestrogens or aromatase inhibitors. However, 30% of patients who receive endocrine therapy will derive no benefit from such treatments and may indeed suffer adverse effects. Currently, there are no ways to predict response to such treatments. ER beta cx, a variant of ER beta, has a dominant-negative effect over ER alpha, and its expression thought to modulate response to endocrine treatment may represent a predictor of response to endocrine therapy. EXPERIMENTAL DESIGN: We investigated the expression of the ER beta cx in 82 frozen breast samples (8 benign, 1 ductal carcinoma in situ, and 73 malignant) by Western blot analysis. The relationship between the expression of ER beta cx variants with prognosis and outcome of endocrine therapy was examined. RESULTS: There was a statistically significant association between the presence of ER beta cx and the response to endocrine therapy (Fisher's exact test, P = 0.04). We also examined the influence of the ER beta cx status of a tumor on time to progression and death. There was a relationship between the presence of ER beta cx and survival, with patients whose tumors express ER beta cx having a longer survival rate (P = 0.05). Cell-type specificity of expression was assessed by immunohistochemistry on a selection of histological samples. CONCLUSIONS: On the basis of this small group of patients, we conclude that the expression of ER beta cx correlated with favorable response to endocrine therapy. A larger study involving the staining of archival material is currently underway to confirm these preliminary results.

Adult↗

PubMed2004

Myoepithelial markers are expressed in at least 29% of oestrogen receptor negative invasive breast carcinoma.

Around 20% of invasive breast carcinoma are oestrogen receptor alpha (ER) negative. Theoretically, this negativity could be either due to the result of downregulation of ER expression in the tumour cells, or the result of the tumour being derived from or differentiating towards cells which normally lack that expression. Normal basal, including myoepithelial, cells of the breast are ERnegative. CD10, smooth muscle actin and S100 are markers of these basal cells that can be used for their demonstration in routinely processed sections. This study was aimed at comparing the incidence of positivity for three myoepithelial markers in ER-negative and ER-positive invasive breast carcinoma. We have examined sections of 117 cases of breast carcinoma, including 77 ER-negative and 40 ER-positive cases, for the expression of CD10, smooth muscle actin and S100, using the avidin-biotin complex immunoperoxidase technique. A tumour was considered positive if more than 10% of the tumour cells were positively stained. In all, 36 (47%) ER-negative tumours were positive for one or more of these myoepithelial markers. The percentage of positively stained tumour cells varied between 30 and 100%. Of the 40 ER-positive tumours, only three (8%) were positive; two for S100 and one for actin, with none being positive for CD10. If cases stained only with S100 are excluded, as some of these may represent luminal differentiation, definite myoepithelial differentiation seems to be present in 29% (22/77) of ER-negative tumours as compared with 2.5% (1/40) of ER-positive tumours; a difference which is highly significant (P<0.001). It is suggested that at least 29% of ER-negative invasive breast carcinomas may be derived from or differentiating along the direction of basal nonconventional luminal epithelial breast cells that normally lack the expression of ER but totally or partially express various myoepithelial markers. Such tumours might need a different therapeutic approach.

Actins↗

PubMed2003

Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer.

Fluorescence lifetime imaging (FLIM) depends on the fluorescence decay differences between tissues to generate image contrast. In the present study FLIM has been applied to fixed (but unstained) breast cancer tissues to demonstrate the feasibility of this approach for histopathological assessment. As the FLIM method relies on natural autofluorescence, it may be possible to circumvent tissue processing altogether and so FLIM has the potential to be a powerful new method of in vivo tissue imaging via an endoscopic or per-operative approach in a variety of organs, as well as a research tool for in vivo animal models of disease. Unstained, alcohol-fixed tissue samples from 13 patients were stimulated by laser pulses at 415 nm. The temporal decay of the autofluorescence was imaged over a period of 2 ns after cessation of the pulse. The decay rate at each image pixel was calculated as the 'lifetime' factor tau. A tissue classification scheme was used to define regions in each image. The average lifetimes of different tissue regions were compared. A total of 167 tissue regions were measured. Within individual fields, stroma had a larger tau (slower decay) than epithelium (p < 0.001). Within individual patients (taking the mean tau of a given tissue type across all fields from each patient), there was a statistically significant difference between benign and malignancy-associated stroma (p < 0.05). Also, benign collagen had a longer tau than benign epithelium (p < 0.05). Multivariate analysis showed a significant difference between benign stroma, malignancy-associated stroma, blood vessels, and malignant epithelium (p < 0.05). Statistically significant differences between benign and malignancy-associated stroma were obtained even with small patient numbers, indicating that lifetime-based instruments can be developed for real-time diagnostic imaging with microscopic resolution.

Breast Neoplasms↗

PubMed2003

Issues in the interpretation of breast core biopsies.

Core biopsies are now widely used for the nonoperative diagnosis of breast masses and microcalcifications and have replaced fine-needle aspiration (FNA) cytology for most lesions in many centers. In the United Kingdom, a scoring system of 5 reporting categories, B1-B5, has been adopted, which is to some extent similar to that used in the interpretation of breast FNA. This article is based on the practice at Charing Cross Hospital, London, which is a major regional breast screening and treatment center covering the West of London area; as well as on a thorough review of the contemporary literature. It begins by discussing issues related to the adoption of the technique and to handling core biopsies, followed by a brief presentation of the reporting categories. The article then deals with some commonly encountered diagnostic problems.

Biopsy↗

PubMed2002

Morphologic spectrum of estrogen receptor-negative breast carcinoma.

CONTEXT: Estrogen receptor (ER)-negative breast carcinomas are a heterogeneous group of breast cancers that are generally thought to be aggressive. OBJECTIVE: To determine the morphologic and immunohistochemical spectrum of a consecutive series of ER-negative breast carcinomas, in an attempt to understand the pathogenesis and behavior of these lesions. DESIGN: Seventy-four consecutive cases of ER-negative invasive carcinomas were studied. Hematoxylin-eosin-stained sections were reviewed, and new sections were stained for c-erbB-2, p53, vimentin, and androgen and prolactin receptors. The findings were correlated with the axillary lymph node status as a measure of tumor aggressiveness. SETTING: The histopathology department of a tertiary referral teaching hospital. RESULTS: The tumors included 50 (68%) invasive ductal carcinomas, 21 (28%) medullary/atypical medullary carcinomas, and 1 each of invasive lobular, apocrine, and papillary carcinoma. Some of the invasive ductal cases had distinctive features that are described in this report. Maximum tumor diameter varied between 5 and 100 mm. Sixty tumors (81%) were grade 3, 13 (18%) were grade 2, and 1 (1%) was grade 1. Of the 60 cases in which the axillary node status was known, 34 (57%) had metastases, and 26 did not. Tumors associated with positive nodes were significantly larger than those associated with negative nodes (37.2 vs 17.8 mm, P <.001). A higher percentage of node-negative tumors were c-erbB-2 positive (42% vs 21%, P <.05). There were no differences between the 2 groups with regard to histologic type, tumor grade, or the expression of p53, vimentin, or androgen or prolactin receptors. CONCLUSIONS: Many ER-negative breast carcinomas have distinctive microscopic features. Not all ER-negative tumors are aggressive, as judged by the absence of lymph node metastases in 43% of cases in this series. Tumor size is the most important indicator for the likelihood of the presence of lymph node metastases. The wide range of tumor sizes encountered in this series suggests that the ER status of a tumor is determined early in its natural history and supports the existence of 2 separate pathways for the development of ER-negative and ER-positive breast carcinomas.

Adult↗

PubMedDate not supplied

Relationship between serum prolactin levels and histology of benign and malignant breast lesions: a detailed study of 153 consecutive cases.

This study was aimed at investigating the relationship between serum prolactin levels and the morphology of operable female breast lesions. One hundred fifty-three consecutive patients with operable benign and malignant breast lesions in whom preoperative serum prolactin levels had been determined were stratified into five groups according to their serum prolactin levels. The histologic findings in these groups were analyzed and compared. Most patients (93%) had serum prolactin levels within the normal limits. Of the 54 patients with benign lesions, only 4(7%) had slightly elevated serum prolactin levels. Two of these patients had fibroadenomas, one had a phyllodes tumor and one had fibrocystic change. Of the 99 patients with carcinoma, 7 (7%) had hyperprolactinemia. Five of the seven tumors were invasive and two were in situ. All seven tumors were of low or intermediate grade of malignancy. The two cases with the highest prolactin levels (3057 and 1822 mU/L) were both intermediate-grade ductal carcinoma in situ (DCIS). It is concluded that the great majority of patients presenting with operable breast lesions have normal serum prolactin levels, and that elevated levels, when present, occur with equal frequency in patients with benign and malignant breast lesions. Hyperprolactinemic patients presenting with carcinoma in this study, none of whom had a history of recent pregnancy or lactation, tended to have histologically low- or intermediate-grade tumors, but this needs to be confirmed by investigating more cases.

Biomarkers, Tumor↗

PubMedDate not supplied

Chest wall tumors presenting as breast lumps.

Two recently seen patients presenting with large breast lumps that proved to be pure mesenchymal tumors arising from the underlying chest wall are presented. One tumor proved to be a giant cell tumor of soft tissue and the other an osteogenic sarcoma. It is suggested that these two cases may not be unique and that some mesenchymal breast tumors might have their origin in the chest wall. Breast computed tomography (CT) scans would help identify similar cases.

Aged↗

PubMedDate not supplied

Idiopathic benign breast calcification.

A 56-year-old woman who came in for screening mammography was found to have extensive unilateral calcification of her left breast which had developed since her previous screening mammogram. The calcification had a ductal and lobular appearance. Possible known etiologies are discussed, but these do not explain the appearance in this case, implying that the cause is idiopathic.

Breast Diseases↗