Search PubMed⌕ Search

Biomedical subjects

N Sneige

Publications and source records attributed to N Sneige.

At least 19 recordsLinked to original sources
PubMed2005

A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding.

The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ER-/HER2- phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA(A)) receptor subunit pi (GABApi, GABRP) in some breast cancers with ER-/HER2- phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABApi gene expression in a separate cohort of 121 invasive breast cancers. GABApi gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABApi gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ER-/HER2- phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABApi in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABApi gene expression was associated with ER-/HER2- phenotype (P < 0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (< or = 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABApi gene expression was also associated with combinations of high grade with ER-/HER2- phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABApi gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

Biomarkers, Tumor↗
PubMed2004

Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.

PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.

Adult↗
PubMed2002

Age as a predictor of outcome for women with DCIS treated with breast-conserving surgery and radiation: The University of Texas M. D. Anderson Cancer Center experience.

PURPOSE: To analyze the long-term outcome of breast conservation therapy in patients with ductal carcinoma in situ (DCIS) in a single institution and to analyze the prognostic importance, if any, of young patient age. METHODS AND MATERIALS: The hospital records of 150 patients with DCIS treated with surgical excision and radiotherapy at our institution between 1980 and 1997 were retrospectively reviewed. For most of the patients, intraoperative specimen radiographs or postoperative mammograms were available for use in assessing that an adequate surgical resection had been performed. The median patient age was 53 years (range 32-81), with 13% of patients or=40 years, p = 0.39). In all cases of local recurrence, patients underwent surgery with or without chemotherapy, and disease control was achieved. CONCLUSION: The results of this study demonstrate high rates of long-term overall survival, disease-specific survival, and local control in patients with DCIS of the breast treated conservatively with segmental mastectomy and radiotherapy. On the basis of the excellent long-term local control and 100% disease-specific survival rates, we found that patient age does not affect the outcome if the margins are clear. Continued studies in young patients treated with breast conservative therapy for DCIS are needed.

Adult↗
PubMed2002

Characterization of foam cells in nipple aspirate fluid.

Foam cells with abundant vacuolated cytoplasm are prominent in most samples of spontaneous nipple discharge, nipple aspirate fluid, and ductal lavage. Although several investigators have attempted to characterize these cells, there is no consensus about whether these cells are derived entirely from macrophages or from both ductal epithelial cells and macrophages. Using immunocytochemical methods, we studied 20 paired specimens of nipple aspirate fluid containing abundant foam cells obtained from the involved breast of women with in situ or invasive carcinoma and from the contralateral normal breast. We used a cocktail of anticytokeratin antibodies including AE1, AE3, and CAM5.2 and the macrophage marker KP1 (CD68). In addition, we examined samples by electron microscopy. The foam cells were consistently negative for cytokeratin and positive for CD68. In every case electron microscopy of these cells revealed irregular outlines with short cytoplasmic processes. The cytoplasm was abundant and contained numerous lysosomes, a small Golgi complex, lipid droplets, mitochondria, and short profiles of rough endoplasmic reticulum. There was no evidence, however, of cell junctions or tonofilaments. The immunocytochemical and electron microscopic findings of our study together clearly support a macrophage derivation for foam cells in nipple aspirate fluid.

Antigens, CD↗
PubMed2001

Paclitaxel in the multimodality treatment for inflammatory breast carcinoma.

BACKGROUND: Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast carcinoma. Anthracycline-based regimens represent the standard of treatment for IBC. Reports of significant clinical activity of paclitaxel in metastatic breast carcinoma led the authors to investigate the role of this drug in the management of IBC. METHODS: Forty-four patients with IBC were enrolled between February 1994 and January 1998. The treatment plan consisted of induction chemotherapy (IC), mastectomy, adjuvant chemotherapy, and radiotherapy. Forty-two patients received IC with four cycles of fluorouracil, doxorubicin, and cyclophosphamide. If the clinical response was less than partial, patients were "crossed over" to paclitaxel before mastectomy. All patients received adjuvant paclitaxel. Patients unresectable after paclitaxel were offered high-dose chemotherapy with autologous peripheral blood progenitor cell support. RESULTS: Thirty-four patients (81%) achieved an objective clinical remission; 3 patients (7%) achieved a clinical complete remission, 31 (74%) a partial remission. Six patients (14%) achieved pathologic complete remission. Sixteen patients were treated with paclitaxel, 7 of them (44%) were able to undergo mastectomy. Median time to progression (TTP) was 22 months. Median overall survival (OS) was 46 months. Concordance between clinical and pathologic response was documented in only 8 patients (24%). No differences in TTP and OS compared with a historical group of 178 IBC patients treated with anthracycline-based regimens. CONCLUSIONS: Paclitaxel improves tumor resectability in anthracycline-refractory IBC. The impact of paclitaxel on the prognosis of IBC needs to be better evaluated in future trials using more dose-intensive schedules of administration. New imaging modalities may contribute to improve assessment of response to IC.

Adenocarcinoma↗
PubMed2001

Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.

PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.

Adenovirus E1A Proteins↗
PubMed2001

Chemotherapy-induced histologic changes in mastectomy specimens and their potential significance.

The aim was to assess chemotherapy-induced histologic changes in breast cancer and to evaluate their relationship with tumour response, to treatment and patient survival. We examined paired pre- and post-chemotherapy tumour specimens from 57 patients with stages II and III breast cancers. All patients received three to four courses of anthracycline-containing preoperative treatment and subsequently underwent modified radical mastectomy 3-5 months after diagnosis. Histologic parameters evaluated included extent of residual disease and cytologic changes in residual tumour and in non-neoplastic breast tissue and lymph nodes. Correlation of pathologic changes with disease-free and overall survival was evaluated. Clinical evaluation indicated that 24% (n=14) of patients had a complete response, 53% (n=30) had a partial response, and 22% (n=13) had stable disease. Pathologic assessment revealed a complete response in 14% (n=8) of patients. Clinical and histologic complete responses were discordant in 35% of patients. Sixty-eight percent of tumours demonstrated moderate to severe cytologic changes in the cytoplasm and nucleus of neoplastic cells. These were characterized by increased overall cell size, cytoplasmic vacuolization, nuclear enlargement, multinucleation, and vesiculation of chromatin. Chemotherapy-induced histologic changes varied within a tumour and between patients. Tumour cytologic changes were significantly associated with histologic (p=0.03) as well as clinical (p=0.02) tumour response. Pathologic tumour response, but not histologic changes, was also a powerful predictor of overall survival and relapse-free survival. In the non-neoplastic glandular tissue, periductal and perilobular fibrosis and atrophy of lobular acini similar to those seen in postmenopausal breast tissue were noted. Changes in lymph nodes were characterized by lymphoid depletion and fibrosis with and without tumour metastasis. Chemotherapy-induced cytologic changes are frequently seen in neoplastic breast epithelium and correlate with response to treatment. Histologic confirmation of clinical tumour response to preoperative chemotherapy is necessary for accurate characterization of patients', response to treatment.

Journal Article↗
PubMed2001

Low-grade (fibromatosis-like) spindle cell carcinoma of the breast.

Spindle cell carcinoma of the breast, a variant of metaplastic carcinoma, includes a wide spectrum of lesions with histomorphologic and nuclear features ranging from overtly malignant to mildly atypical. Spindle cell carcinomas with mildly atypical features may resemble fasciitis, fibromatosis, or myofibroblastic tumors and therefore are often misinterpreted as such. A recent study has suggested that spindle cell carcinomas with a dominant fibromatosis-like phenotype, unlike spindle cell carcinomas in general, have no propensity for distant metastasis and should be termed "tumors" rather than "carcinomas." To investigate the question of fibromatosis-like spindle cell breast carcinoma (FLSpCCs) metastatic potential, we studied cases of FLSpCC seen at the University of Texas M.D. Anderson Cancer Center between 1987 and 2000. Clinical, pathologic, and immunophenotypic features were reviewed, with emphasis on biologic behavior and predictors of clinical outcome. Our series included 24 women who ranged in age from 55 to 85 years (mean 66 years). Tumor size ranged from 1.0 to 5 cm (mean 2.8 cm). Most tumors were grossly well defined but had microscopic infiltrative borders. Tumors showed a dominant fibromatosis-like or myofibroblastic-like growth pattern with prominent collagenization. Inflammatory infiltrate was noted in the majority of tumors. Cytokeratin-positive cells were seen in all cases and usually appeared as cords or sheets of polygonal cells; isolated cytokeratin-positive cells were rare. In most tumors immunoreactivity for smooth muscle actin (SMA) was confined to the cytokeratin-negative cells. In five cases intense co-expression of cytokeratin and SMA was noted. None of the tumors showed immunoreactivity for smooth muscle heavy chain myosin, estrogen receptors, progesterone receptors, or HER-2/neu. Ki-67 expression was noted in fewer than 5% of tumor cells. Treatment consisted of local excision (seven cases) or modified radical mastectomy (13 cases). Treatment was unknown in four cases. In patients who underwent axillary nodal dissection, no lymph node metastases were found. Two of the six patients who underwent local excision developed local recurrence. Two patients who underwent modified radical mastectomy developed lung metastases within 2 years after the initial diagnosis. The metastatic tumors were histologically similar to the primary tumors. Our findings indicate that FLSpCCs have the potential for local recurrence and distant metastasis and should be treated accordingly. Because FLSpCCs may be underdiagnosed as benign, the use of immunohistochemical studies, especially for cytokeratins and SMA, is essential in the evaluation of any spindle cell proliferations of the breast.

Actins↗
PubMed2001

Fine-needle aspiration biopsy of nonpalpable breast lesions in a multicenter clinical trial: results from the radiologic diagnostic oncology group V.

PURPOSE: To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine-needle aspiration biopsy (FNAB) in the diagnosis of nonpalpable breast lesions. MATERIALS AND METHODS: At 18 institutions, 442 women who underwent 22-25-gauge imaging-guided FNAB were enrolled. Definitive surgical, core-needle biopsy, and/or follow-up information was available for 423 (95.7%) of these women. The reference standard was established from additional clinical and imaging information for an additional six (1.4%) women who did not undergo further histopathologic evaluation. The FNAB protocol was standardized at all institutions, and all specimens were reread by one of two expert cytopathologists. RESULTS: When insufficient samples were included in the analysis and classified as positive, the sensitivity and specificity of FNAB were 85%-88% and 55.6%-90.5%, respectively; accuracy ranged from 62.2% to 89.2%. The diagnostic accuracy of FNAB was significantly better for detection of masses than for detection of calcifications (67.3% vs. 53.8%, P =.006) and with US guidance than with stereotactic guidance (77.2% vs. 58.9%; P =.002). CONCLUSION: FNAB of nonpalpable breast lesions has limited value given the high insufficient sample rate and greater diagnostic accuracy of other interventions, including core-needle biopsy and needle-localized open surgical biopsy.

Biopsy, Needle↗
PubMed2001

Molecular and biomarker analyses of salivary duct carcinomas: comparison with mammary duct carcinoma.

Salivary duct carcinoma (SDC) is a rare high-grade aggressive neoplasm that manifests close histologic features with invasive ductal carcinoma of the breast (IDC). In contrast to SDC, extensive molecular studies have been performed on IDC and led to the identification of certain biological markers. To investigate the underlying molecular and biologic characteristics of SDC, we performed molecular analyses using microsatellite markers on chromosomal arms 6q, 16q, 17p, and 17q, DNA flow cytometry and immunohistochemical staining for androgen receptor (AR) and p53 expression on 28 examples of these tumors in comparison to 24 IDC cases. Our results show that generally similar allelic alterations, elevated p53 and androgen receptor expressions, and high frequency of DNA aneuploidy are manifested in both SDCs and IDCs. Differences at certain markers on 6q, 17p and 17q chromosomal loci, however, were observed between the two entities. Certain loci on 6q were more frequently altered in SDC than IDC which loci on chromosomes 17p and q arms were more seen in IDCs than SDCs. The majority of SDCs had high AR expression while most of IDCs were AR negative. Our study indicates that: i) SDC may share some genetic alterations with IDC, ii) high AR expression in SDC may play a role in tumor progression, and iii) p53 overexpression and DNA aneuploidy in both entities reflect their aggressive behavior.

Adult↗
PubMed2001

Quantitative nuclear morphometry by image analysis for prediction of recurrence of ductal carcinoma in situ of the breast.

Clinical management of ductal carcinoma in situ (DCIS) remains a challenge because significant proportions of patients experience recurrence after conservative surgical treatment. Unfortunately, it is difficult to prospectively identify, using objective criteria, patients who are at high risk of recurrence and might benefit from additional treatment. We conducted a multi-institutional, collaborative case-control study to identify nuclear morphometric features that would be useful for identifying women with DCIS at the highest risk of recurrence. Tissue sections of archival breast tissue of 29 women with recurrent and 73 matched women with nonrecurrent DCIS were stained for DNA, and nuclei in the DCIS lesions were evaluated by image analysis. A clear correlation between mean fractal2_area (FA2) and nuclear grade was observed (P < 0.001), allowing an objective determination of nuclear grade. Several nuclear morphometric features, including mean and variance of variation of radius, mean area, mean and variance of frequency of high boundary harmonics (FQH), and variance in sphericity, were found to be useful in discriminating recurrent from nonrecurrent DCIS subjects. However, the nuclear features associated with recurrence differed between high- and low-grade lesions. For lesions with high FA2 (nuclear grade 3), mean variation of radius, mean FQH, and mean area alone yielded recurrence odds ratios of 4.55 [95% confidence interval (CI) 0.45-45.96], 3.86 (95% CI, 0.88-16.98), 2.90 (95% CI, 0.31-27.2), respectively. Using a summed feature model, high-FA2 lesions showing three poor prognostic features had an odds ratio of 15.63 (95% CI, 1.22-200), compared with those with zero or one poor prognostic feature. Lesions with low mean FA2 (nuclear grade 1 or 2) showing high variances in sphericity and FQH had an odds ratio of 7.71 (95% CI, 1.77-33.60). Addition of other features did not enhance the odds ratio or its significance. These results suggest that nuclear image analysis of DCIS lesions may provide an adjunctive tool to conventional pathological analysis, both for the objective assessment of nuclear grade and for the identification of features that predict patient outcome.

Adult↗
PubMed2001

Computerized image analysis of Ki-67 in ductal breast carcinoma in situ.

OBJECTIVE: To develop and determine the staining protocols and computerized image analysis methods that are the most effective combination for performing quantitative analysis of Ki-67. STUDY DESIGN: We compared conventional bright-field light microscopy and refractive optical enhancement methods in combination with various immunodetection and filter enhancement methods, including immunogold in combination with epipolarization refractive optics and enzymatic conversion of chromogenic substrates in combination with optical filter enhancement. Initial Ki-67 tests were performed on lymph node tissues and cultured human breast cells and then applied to 200 ductal carcinoma in situ (DCIS) samples. DCIS acini were digitally acquired, and a region of interest was manually outlined in each one with a digital stylus to include only the cellular component; then the Ki-67 staining index was quantified by segmentation analysis. RESULTS: Although combining epipolarization analysis with immunohistogold staining was the most sensitive detection method, nonspecific binding was too high. The streptavidin-horseradish-peroxidase enzymatic conversion of 3,3'-diaminobenzidine (DAB) in combination with optical enhancement filters was the most effective method tested. Ki-67 stain was associated with dense fibrillar structures of the nucleoli in the less intensely staining nuclei and was most intense in paired nuclei. CONCLUSION: The method of measuring Ki-67 expression by DAB staining combined with optical enhancement filters and quantification via computer-assisted image analysis techniques produced objective and reproducible results. As such, this method can offer (1) less intraobserver and interobserver variability, (2) a digital archival record, and (3) a baseline for digital exchange of information between studies.

Antibodies, Monoclonal↗
PubMed2000

Distinction of phyllodes tumor from fibroadenoma: a reappraisal of an old problem.

BACKGROUND: Using fine-needle aspiration (FNA) smears, it is difficult to distinguish low grade phyllodes tumor (PT) from fibroadenoma (FA) due to overlapping cytologic features between the two lesions. The authors retrospectively studied 45 histologically proven fibroepithelial breast tumors of which 33 were FA and 12 were PT (1 malignant, 8 borderline, and 3 benign) to define cytologic features that can help in the accurate categorization of these lesions by using FNA samples. METHODS: The cytologic features analyzed included: 1) epithelial component for number (<5 or >5), architecture, apocrine metaplasia, squamous metaplasia, nuclear pleomorphism, and mitosis; 2) stromal fragments for number (<5 or >5), cellularity (on a scale of 1+ to 3+), borders, cell characteristics, nuclear pleomorphism, and mitosis; 3) individual dispersed stromal cells in the background for cellularity (on a scale of 1+ to 3+), and cellular shape (short/round/oval or long spindle) based on whether they were smaller or larger than 2 times the size of a small round lymphocyte. RESULTS: The mean age of patients with FA was 34 years and of those with PT 44 years. The average size of FA was 2.0 cm, and the average size of PT was 4.0 cm. The characteristics of the epithelial fragments of PT and FA were not significantly different. Stromal fragments were noted in 60% of FA and 83% of PT samples examined. Fifty-six percent of PT and 30% of FA exhibited hypercellular stromal fragments (3+ cellularity), and the difference was not statistically significant. Large club-shaped hypercellular stromal fragments were present only in FA (in 21% of the samples). There was no difference in the overall cellularity of the background stromal nuclei in the two types of lesions. Long spindle nuclei averaging greater than 30% of the dispersed stromal cell population in the background were found only in cases of PT (in 57% of the samples; P < 0.001). Short/round/oval nuclei characterized most FAs. Long spindle nuclei constituting 10-30% of the dispersed stromal cells, however, occurred in both PT and FA to the extent of 43% and 21%, respectively. CONCLUSIONS: Hypercellular stromal fragments occur not only in PT, but also in FA, and hence they cannot be used as the sole criterion for making a diagnosis of PT on FNA. The proportion of individual long spindle nuclei (>30%) amid the dispersed stromal cells in the background is the most reliable discriminator between the two lesions. Lesions in which long spindle nuclei constitute between 10% and 30% may represent either PT or FA, and therefore such lesions should be categorized as indeterminate on FNA.

Adult↗
PubMed2000

Epithelial cells and other cytologic features of pseudomyxoma peritonei in patients with ovarian and/or appendiceal mucinous neoplasms: a study of 12 patients including 5 men.

BACKGROUND: Pseudomyxoma peritonei (PP) is a rare condition. Cytologic evaluation of peritoneal fluid often is an initial diagnostic test for possible ovarian and/or appendiceal primary tumors. Previous studies suggest that patients with PP who have epithelial cells (ECs) in their peritoneal fluid usually have a less favorable prognosis than patients with acellular PP. To the authors' knowledge, few reports of PP in the cytologic literature cite the presence of ECs. METHODS: Twelve cases of PP diagnosed by cytologic examination at the University of Texas M. D. Anderson Cancer Center over 15 years were identified. In all cases, primary tumors were confirmed histologically. All available cytologic smears and cell block sections were reviewed for cytomorphology, with particular attention given to the presence of ECs. A correlation between the presence of ECs and patient outcome also was sought (median follow-up, 26 months). RESULTS: Two patients had ovarian neoplasms, six patients (one female and five males) had appendiceal neoplasms, and four patients had synchronous ovarian and appendiceal tumors. Cytologic features included mucin pools (12 of 12 patients), ECs (11 of 12 patients), mesothelial or mesothelial-like cells (10 of 12 patients), histiocytes (11 of 12 patients), and fibroblast-like or spindle cells (6 of 12 patients). ECs were columnar with mucinous features in the majority of cases, and the number of ECs in each case was variable, ranging from 1+ (rare) to 3+ (many). Of the 11 patients with available follow-up data, 6 had recurrent disease, 4 had persistent disease, and 1 patient with acellular PP was alive without clinical evidence of disease after 24 months of follow-up. CONCLUSIONS: Unlike previous PP cytology reports, the current study frequently identified ECs (92%). Because of the potential prognostic implication of ECs in patients with PP, a diligent search for ECs is warranted. Indication of the presence or absence of ECs in the cytology report may be useful when PP is diagnosed.

Adenocarcinoma, Mucinous↗