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N Sneige

Publications and source records attributed to N Sneige.

At least 55 records · Page 3Linked to original sources

Correlation of interleukin 6 with interleukin 1alpha in human mammary tumours, but not with oestrogen receptor expression.

The authors hypothesized that IL-6 production by breast tumour tissues would correlate with OR-positivity, as only those tumours that contain oestrogen receptors (OR) and use oestrogen as a mitogen would benefit from locally increased oestrogen. IL-6 increases the activity of the 17beta-oxidoreductase, which converts oestrone to oestradiol, a process that may contribute to the increased concentration of oestrogen around breast tumours. IL-1alpha upregulates IL-6 production; therefore, the correlation between IL-1alpha and IL-6 immunoreactivity and OR-positivity in paraffin-embedded human breast tumours was further investigated.The results indicate IL-6 immunoreactivity in 40 of 66 paraffin embedded breast tumour specimens, a finding which did not correlate with the clinical evaluation of oestrogen receptor positivity (P=0.32 by Fisher's exact test). However, there was a correlation between IL-6 and IL-1alpha immunoreactivity (P<0.05). To study an in vitro model for this phenomenon, the IL-6 immunoreactivity in available cell lines was tested. Surprisingly, no production of IL-6 protein or mRNA could be detected in any of the cell lines, and this did not change with IL-1alpha stimulation. Therefore, none of the cell lines apparently reflected the immunological potential observed in the majority of surgical specimens.

Breast Neoplasms↗

Progressive decrease in nuclear retinoic acid receptor beta messenger RNA level during breast carcinogenesis.

Some of the nuclear retinoic acid receptors (RARs) alpha, beta, and gamma and retinoid X receptors (RXRs) alpha, beta, and gamma are thought to mediate the effects of retinoids on cell growth, differentiation, and apoptosis and thereby prevent breast carcinogenesis. We analyzed the expression of mRNAs for the three RARs and RXR-alpha in histological sections of specimens from 70 breast cancer patients, which included adjacent normal tissue, ductal carcinoma in situ, and invasive cancer, using in situ hybridization. RARs alpha, beta, and gamma and RXR-alpha were expressed in 98.1, 98.0, 93.0, and 100% of the adjacent normal tissues. Significant decreases in the number of cases expressing RAR-beta were observed among ductal carcinoma in situ (83.1%) and invasive carcinomas (51.6%), especially among the poorly differentiated cases (77.4 and 35.7 %, respectively). No relationship was found between the expression of estrogen receptor and RAR-beta. These results implicate decreases in RAR-beta expression in breast cancer development and suggest that they are independent of estrogen receptor status.

Breast↗

Sources of diagnostic error in the fine-needle aspiration diagnosis of Warthin's tumor and clues to a correct diagnosis.

Squamous metaplasia and cystic degeneration in Warthin's tumor (WT) are not uncommon. A recent case of WT misdiagnosed as metastatic squamous carcinoma with cystic change prompted us to review our experience with fine-needle aspiration (FNA) of WT, with special attention given to potential sources of diagnostic pitfalls. Aspirations from 16 cases of histologically confirmed WT were retrospectively evaluated for cellularity, cell composition, and background. The FNA review diagnosis was compared with the previous FNA and corresponding tissue findings. All tumors presented in the parotid gland. The initial cytologic diagnoses were: WT in 13 cases, oncocytoma vs. low-grade mucoepidermoid carcinoma in 1, squamous carcinoma vs. branchial cleft cyst in 1, and squamous carcinoma in 1. On review, 13 cases (81%) showed typical features associated with WT: Moderate to abundant oncocytic epithelium, lymphoid stroma, background debris, and mild squamous metaplasia. In the remaining cases, one lacked a lymphoid stroma and could not be further classified (initially called "oncocytoma vs. low-grade mucoepidermoid carcinoma"). The other 2 cases contained moderate to abundant atypical squamous cells and extensive necrotic/mucoid debris, and review diagnoses were consistent with the initial cytologic diagnoses (squamous carcinoma in one, and branchial cleft cyst vs. squamous carcinoma in the other). In our series, typical features of WT were seen in 81% of cases. Atypical features are largely present as individual metaplastic squamous cells. Diagnostic errors are caused by a lack of typical features and the presence of individual atypical squamous cells in a necrotic background mimicking carcinoma. An awareness of the morphologic variation present on cytologic preparations and correlation with clinical findings should prevent erroneous interpretation in the FNA setting.

Adenolymphoma↗

Impact of extensive intraductal component on recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy.

BACKGROUND: The relationship between an extensive intraductal component (EIC) and recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy has not been clearly defined. METHODS: 133 patients with stage I or II breast cancer who underwent breast conservation therapy between 1978 and 1990 at The University of Texas M. D. Anderson Cancer Center were retrospectively studied. All pathology slides were reviewed to determine tumor size, nuclear grade, extent of intraductal component, number of positive lymph nodes, and histologic margins. EIC was defined as ductal carcinoma in situ (DCIS) occupying 25% or more of the area encompassed by the infiltrating tumor and DCIS present in grossly normal adjacent breast tissue. RESULTS: 110 patients are alive, and 23 have died, with a median follow-up of 7 years; 85 of 133 patients had an intraductal component, but only 18 had an EIC. Locoregional control and disease-free and overall survival were not adversely affected by the presence of an EIC. Five of 133 patients had a locoregional recurrence, but only one had an EIC. CONCLUSIONS: EIC, if negative margins can be achieved, does not adversely affect disease-free or overall survival or local control rates.

Adult↗

Intraluminal crystalloids in breast carcinoma. Immunohistochemical, ultrastructural, and energy-dispersive x-ray element analysis in four cases.

OBJECTIVE: Intraluminal crystalloids have been described in the prostate, salivary gland, and ovary, but have not yet been reported in the breast. We report four cases of breast carcinoma in which these crystalloids were found in ducts with intraductal carcinoma or atypical hyperplasia. The presence of intraluminal crystalloids may be a useful adjunct in making a diagnosis of carcinoma or may be a feature to look for as a marker for the presence of carcinoma. DESIGN: Four cases of breast carcinoma containing intraluminal crystalloids were identified among 6900 surgical breast specimens between January 1990 and June 1995 at M. D. Anderson Cancer Center, Houston, Tex. Those sections with crystalloids identified by hematoxylin-eosin stain were stained with periodic acid-Schiff, Alcian blue, and mucicarmine stains. Immunohistochemical and ultrastructural studies and energy-dispersive x-ray analysis were also performed on these sections. RESULTS: The intraluminal crystalloids were eosinophilic, varied in shape and size, and did not exhibit birefringence under polarized light. Immunohistochemically, the crystalloids were negative for keratin, muscle-specific actin, and kappa and lambda light chains, but the surfaces stained positively for epithelial membrane antigen. By electron microscopy, the crystalloids had no limiting membrane and were composed of an electron-dense material with no discernible periodicity. By energy-dispersive x-ray element analysis, the crystalloids had no mineral content; however, sulfur was found, indicating a protein content. CONCLUSIONS: The pathogenesis and constituents of these intraluminal crystalloids remain to be determined. Inasmuch as intraluminal crystalloids have not been found in normal ducts or acini, or in ductal hyperplasia without atypia, their presence may serve as a marker for breast carcinoma.

Adult↗

In search of specimen adequacy in fine-needle aspirates of nonpalpable breast lesions.

Pathology-related medical malpractice claims frequently concern fine-needle aspirations (FNAs) of breast lesions, and diagnostic errors have been attributed in part to the inadequacy of the specimens. Cytologic criteria for adequate FNA specimens, specifically in cases without malignancy, have not been clearly defined. From January 1988, to August 1995, 669 ultrasonographic-guided FNAs of nonpalpable, solid breast lesions with subsequent histologic examination were performed at our institution. From these, 54 cases with cytologic diagnoses of insufficient or nonspecific benign findings were identified. All aspirates were reviewed, and the number and size of the epithelial cell groups were quantitated in each case. By using criteria for adequate aspirates of palpable breast lesions (six or more epithelial cell groups per case with a minimum of 5-10 cells per group), 23 of the 54 aspirates were deemed inadequate and 31 adequate. Eleven (48%) of the inadequate aspirates and 17 (55%) of the adequate aspirates were from histologically confirmed carcinomas (ductal carcinoma in situ, 6; invasive carcinoma, 22, of which 12 were ductal, 7, lobular, and 3, mixed ductal and lobular). For the mammographic diagnoses "probably benign," "indeterminate," and "suggestive of malignancy or malignant," the probability of malignancy in aspirates of adequate cellularity (eg, > 6 epithelial groups) was 9%, 40%, and 93%, respectively. These findings indicate that a significant proportion of breast aspirates still may yield false-negative results despite adequate to high cellularity. Although a definition of adequacy based on cellularity is useful in reducing false-negative results, cellularity alone cannot be relied on in the management of nonpalpable lesions. For mammographic findings that are indeterminate or suggestive of malignancy or malignant, nonspecific FNA findings should be followed by core or excisional biopsy to exclude carcinoma.

Adult↗

Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma.

The purpose of this study was to correlate physical examination and sonographic and mammographic measurements of breast tumors and regional lymph nodes with pathological findings and to evaluate the effect of neoadjuvant chemotherapy on clinical Tumor-Node-Metastasis stage by noninvasive methods. This was a retrospective analysis of 100 patients with locally advanced breast cancer registered and treated in prospective trials of neoadjuvant chemotherapy. All patients received four cycles of a doxorubicin-containing regimen and had noninvasive evaluation of the primary tumor and regional lymph nodes before and after neoadjuvant chemotherapy by physical examination, sonography, and mammography and underwent breast surgery and axillary dissection within 5 weeks after completion of neoadjuvant chemotherapy. The correlations between clinical and pathological measurements were determined by Spearman rank correlation analysis. A proportional odds model was used to examine predictive values. Eighty-three patients had both a clinically detectable primary tumor and lymph node metastases. Sixty-four patients had a decrease in Tumor-Node-Metastasis stage after chemotherapy. For 54% of patients, there was concordance in clinical response between the primary tumor and lymph node compartment; for the rest, results were discordant. Physical examination correlated best with pathological findings in the measurement of the primary tumor (P = 0.0003), whereas sonography was the most accurate predictor of size for axillary lymph nodes (P = 0.0005). The combination of physical examination and mammography worked best for assessment of the primary tumor (P = 0.003), whereas combining physical examination with sonography gave optimal evaluation of regional lymph nodes (P = 0.0001). In conclusion, physical examination is the best noninvasive predictor of the real size of locally advanced primary breast cancer, whereas sonography correlates better with the real dimensions of axillary lymph nodes. The combination of physical examination with either mammography or sonography significantly improves the accuracy of noninvasive assessment of tumor dimensions.

Adult↗

Can core needle biopsy replace fine-needle aspiration cytology in the diagnosis of palpable breast carcinoma. A comparative study of 124 women.

BACKGROUND: There appears to be a growing movement in favor of core needle biopsy (CNB) over fine-needle aspiration (FNA) cytology in detecting breast carcinoma in women. The authors compared the sensitivity and specificity of these two methods in patients who presented to The University of Texas M. D. Anderson Cancer Center for evaluation of a palpable breast mass. METHODS: One hundred and twenty-four women (mean age, 51 years; range, 28-86 years) with a clinically suspicious palpable mass (mean size, 4.4 cm; range, 1-12 cm) underwent concurrent FNA and CNB. For the FNA, an average of three needle passes were made. FNA was followed by three CNBs using the Bard Monopty needle. CNB samples were submitted for frozen section to determine adequacy, and an additional three cores were performed if the first batch was deemed inadequate. All patients ultimately had histologic confirmation of their neoplasms either by the core needle procedure or by definitive open surgical biopsy. Features of cases with discrepant diagnoses were examined in relation to tumor size and histologic type. RESULTS: Specificity of both FNA and CNB was 100%. The sensitivity in detecting a malignant neoplasm was higher for FNA than for CNB (97.5% vs. 90%, P < 0.004). CONCLUSIONS: In our experience, FNA of palpable breast lesions is a more sensitive method for the detection of carcinoma regardless of tumor type, size, or differentiation. Contrary to other reports, not only was FNA alone more sensitive than CNB alone, the addition of CNB to an already negative FNA failed to increase sensitivity in the detection of carcinoma. However, CNB did contribute to a more definitive diagnosis in some cases. The authors also found FNA to be more cost effective than CNB for palpable breast lesions when time and effort are taken into consideration. This reinforces the benefit of FNA over CNB in the detection of early stage breast carcinoma.

Adult↗

Flow cytometric analysis of apoptosis and bcl-2 in primary breast carcinomas: clinical and biological implications.

Analysis of programmed cell death (apoptosis), of bcl-2, a critical regulator of this process, and of the proliferative fraction may provide detailed information on the biologic characteristics of tumor cell populations. To investigate the potential role of these parameters in assessing mammary carcinoma, we adapted flow cytometric procedures for concurrent measurement of apoptosis, bcl-2 expression, and cell proliferation in 54 primary breast carcinomas and correlated the findings with traditional clinicopathologic information. Overall, a significant inverse relationship between apoptosis levels and bcl-2 expression was observed (P = 0.005). Apoptosis levels correlated significantly with DNA aneuploidy (P = 0.03) and S + G2M fractions (P = 0.005) of these tumors. A significant correlation between bcl-2 expression and estrogen receptor positivity (P = 0.05) and DNA diploidy (P = 0.02) was noted. Bcl-2 expression, however, was inversely correlated with S + G2M fractions (P = 0.001). We conclude that analysis of apoptosis and bcl-2 by flow cytometry allows further characterization of tumor cell populations that may be useful for prognostic and therapeutic management of breast carcinoma.

Adult↗

Fine-needle aspirates of granular cell lesions of the breast: report of three cases, with emphasis on differential diagnosis and utility of immunostaining for CD68 (KP1).

Fine-needle aspiration biopsy (FNA) has been recognized as a safe and reliable procedure for evaluating breast lesions. We herein report cytologic findings for needle aspirates from three granular cell nodules of the breast. The nodules were detected by diagnostic imaging and ranged from 0.6 to 1 cm in diameter. Ultrasound-guided FNA was used in all cases and revealed cellular aspirates with similar cytomorphologic features consisting of sheets of large granular cells intersected by arborizing thin-walled blood vessels. The cells had round to oval nuclei, inconspicuous nucleoli, and abundant, often ill-defined granular cytoplasm. Tissue sections of resected specimens yielded final diagnoses of granular cell metaplasia of histiocytes and stromal cells in one case and granular cell tumor (GCT) in the other two cases. FNA smears in all three cases were strongly positive for the lysosomal marker CD68 (KP1) and S-100 protein; therefore, it was not possible to distinguish true GCT from granular cell metaplasia/granular histiocytes. When breast aspirates reveal granular cell changes, excisional biopsy should be done for a definitive diagnosis.

Adult↗

Technical approach for the study of the genetic evolution of breast cancer from paraffin-embedded tissue sections.

We have optimized a technique that allows the study of numerous chromosomal loci (n = 20-50) from single paraffin-embedded tissue sections by microsatellite length polymorphism analysis. DNA samples from normal and breast cancerous tissue can be obtained from the same section by means of microdissection. This technique was further improved by subjecting DNA to several cycles of amplification with a degenerate (universal) primer and then with specific microsatellite primers. This amplified DNA was also used to screen for mutations in the p53 gene by means of PCR-SSCP. In addition adjacent tissue sections were used to assess specific chromosome copy number by interphase cytogenetic analyses (chromosome in situ hybridization) and to analyze expression of specific genes such as p53 and ERBB2. As an example of the use of our approach we performed a detailed chromosome 17 allelotypic analysis in 22 breast tumors (5 ductal carcinomas in situ, 13 invasive ductal carcinomas, and 4 invasive lobular carcinomas). We detected mutations in the p53 gene by PCR-SSCP in 36% of the samples. Samples with significant levels of p53 protein accumulation detected by immunohistochemistry were also positive for mobility shifts in the SSCP analysis. We observed that chromosome 17 allelic losses and imbalance occurred at as early a stage as ductal carcinoma in situ (DCIS). Although in some cases we observed allelic losses or imbalance affecting the 17p13 region, close to the p53 locus, several of the tumors showed dissociation between such loss or imbalance and p53 mutation. Lobular carcinomas were predominantly disomic for chromosome 17 in contrast with ductal tumors, which often showed polysomy for chromosome 17. This comprehensive approach correlating the tumor subtype, its allelotype, with specific chromosome copy number and specific gene mutations and expression in preinvasive or early invasive breast cancer lesions will potentially provide information of relevance for a better understanding of the multistep mechanisms of breast carcinogenesis.

Alleles↗

Abnormal expression of MDM-2 in breast carcinomas.

MDM-2 is a cellular oncoprotein that binds to the p53 protein and abrogates its growth-suppressing function. At least seven MDM-2 mRNAs and five proteins (p90, p85, p76, p74, and p57) have been reported in tissue culture. MDM-2 gene amplification occurs in human sarcomas and high-grade gliomas. MDM-2 overexpression without gene amplification has been reported in leukemias and lymphomas. Here we report MDM-2 mRNA overexpression in 24 (73%) out of 33 cases of human breast carcinoma as compared with normal breast tissue. The MDM-2 overexpression was seen in the absence of MDM-2 gene amplification. MDM-2 protein expression was studied by western blot analysis in 21 of these cases of carcinoma. We found complete concordance between MDM-2 mRNA overexpression and MDM-2 protein levels. MDM-2 proteins were overexpressed in 15 of 21 breast carcinoma tissue samples but not in normal breast tissue controls. Ten of these fifteen cases overexpressed MDM-2 p57 protein, two cases overexpressed both p57 and p90, and three cases overexpressed only p90. MDM-2 overexpression was confirmed by immunohistochemistry. p53 overexpression was also studied by immunohistochemistry, 69% of breast carcinomas that overexpressed the MDM-2 mRNA had detectable nuclear p53 protein. These findings demonstrate that MDM-2 oncoprotein expression is altered in primary human breast carcinomas at both mRNA and protein levels. In addition, our results suggest that MDM-2 p57 protein represents the main MDM-2 protein altered in breast carcinomas.

Blotting, Western↗

Interphase cytogenetics in mammographically detected breast lesions.

Chromosomal aneuploidy in 25 mammographically detected breast lesions (MDBL) were determined on cytological smears using directly labeled pericentromeric probes for chromosomes 7 to 12, 17, 18 and X. The lesions included seven nonproliferative (NP) lesions, seven atypical hyperplasias (AHs), and 11 carcinomas (CAs). No other significant histological findings were identified in the remaining specimens except in two mammographically detected NP lesions, where foci of AH were present in adjacent sections; therefore, these two specimens were included in the AH lesion group (moderately increased risk lesions). Corresponding tissue sections were evaluated, and the results were correlated with fluorescent in situ hybridization (FISH) results. Monosomy was defined as the loss of one signal in > or = 15% of cells, and trisomy or tetrasomy was defined by the presence of three or more signals in > or = 3% of cells. Chromosomal aberrations were detected in 2 of 5 NP, 9 of 9 AH, and 11 of 11 CA groups. The mean number of cells with three or more signals, for all chromosomes, was 1.04 +/- 0.9 in the NP group, 8.5 +/- 9.4 in the AH group, and 20.2 +/- 5.4 in the CAs. A significant statistical difference was noted between the different groups (P = .0001). Chromosomal gain was the most common aberration and involved all chromosomes. The X chromosome was the only individual chromosome with significant differences in NP, AH, and CA groups. Chromosomal loss was observed in five specimens (20%) and involved chromosomes 8, 10, 17, and 18. The authors conclude (1) significant chromosomal aberrations can be detected in AH lesions and in NP epithelium from patients with moderately increased risk lesions; (2) numerical chromosomal aberrations tend to increase with progression of disease; (3) the frequent chromosomal gains/losses involving AH suggest that some AH may display submicroscopic features of malignancy; and (4) combined chromosomal aberrations allow for significant categorization of breast lesions, especially in cytology specimens.

Adult↗

Bivariate RNA and DNA content analysis in breast carcinoma: biological significance of RNA content.

Flow cytometric studies of mammary carcinoma have been limited to DNA content analysis. Simultaneous analysis of DNA and RNA has been applied to hematological and certain solid neoplasms and has been shown to provide valuable information in the clinical assessment of these tumors. To determine whether measuring RNA content during flow cytometric analysis provides additional information in the clinical assessment of breast carcinoma, dual-parameter analysis of DNA and RNA content on freshly disaggregated breast carcinoma specimens was performed. RNA content, divided along the mean (</=1.6 and >1.6), correlated with tumor grade, histological type, hormonal status, and patient survival. DNA aneuploidy was noted in 247 (69.2%) neoplasms and correlated significantly with tumor grade and stage but not with clinical outcome. The proliferative fraction, defined as S + G2-M and dichotomized along the mean value (</=10% and >10%), correlated significantly with tumor grade, size, hormonal status, lymph node involvement, and survival. Cox's proportional hazard analysis revealed that RNA content, proliferative fraction, and tumor stage are independent prognostic indicators. Our results indicate that measurement of cellular RNA content provides additional biological information that may be useful in the clinical assessment of breast carcinoma.

Adult↗

Fine-needle aspiration cytology of seminoma: a review of 16 cases.

We report the cytomorphologic features of 16 fine-needle aspiration (FNA) biopsies of seminoma obtained from 16 male patients. The aspirates included two primary gonadal tumors (one occurring in a cryptorchid testis), two primary mediastinal tumors, and 12 metastases (two with unknown primaries). Analysis of the aspirates revealed a primarily dispersed cell population of large cells with scant to moderately abundant cytoplasm. The nuclei were round to slightly irregular, had finely granular chromatin, and had either one central prominent nucleolus or two to three smaller nucleoli. Variable numbers of lymphocytes and plasma cells were intermingled with the tumor cells. Only a few cases had epithelioid histiocytes or the characteristic "tigroid" background. The cytologic features of the metastases were distinctive and were considered diagnostic for therapeutic management. In six cases, an initial diagnosis of seminoma by FNA biopsy identified the neoplasm as germ cell in origin rather than other neoplasms in the differential diagnosis, thereby expediting therapeutic management.

Adult↗

Ductal carcinoma in situ treated with lumpectomy and irradiation: histopathological analysis of 49 specimens with emphasis on risk factors and long term results.

Forty-nine women with ductal carcinoma in situ (DCIS) treated with lumpectomy and irradiation were studied retrospectively. The median age was 50 years (range, 29 to 73 years) and the median follow-up time from initiation of therapy was 86 months (range, 17 to 230 months). Twelve patients presented with palpable masses (0.4 to 4 cm), three with breast thickening, and three with nipple discharge. In 31 patients the tumors were detected by mammography. Intraoperatively, excision of lesions was confirmed by specimen x-ray (38 specimens) or gross inspection (five specimens) and was recorded to be complete. No record was available in the other six patients. Margins of excision free of DCIS were microscopically confirmed in 25 specimens. The size of impalpable DCIS lesions recorded in 25 patients ranged from 0.4 to 5.0 cm (mean, 1.5 cm). Using Lagios' classification system, there were 18 classic comedocarcinomas, high nuclear grade (NG) with necrosis; seven cribriform/papillary, high NG with necrosis; 17 cribriform/micropapillary, intermediate NG with or without necrosis; and seven cribriform/micropapillary, low NG without necrosis. In two patients residual malignant calcifications were present on the postoperative mammogram. Disease recurred in the treated breast at the site of incision in five patients at 18 months and 8, 11, and 12 (two patients) years from initial therapy. The rate of local disease recurrence was 2% at 5 years and 6% at 10 years; three recurrences showed invasive ductal carcinoma and two were DCIS. To evaluate risk factors the following characteristics were considered: necrosis, NG, histological type, periductal fibrosis, periductal lymphoid infiltrate, margin status, age, and method of tumor detection. The end points chosen were recurrence and death from any cause (because only one patient died of disease). Although the recurrences were attributed to residual disease in two patients, of the clinical and pathological parameters evaluated, only periductal fibrosis showed a significant relationship with outcome, with a P value < or = .05 by the Wilcoxon test. On the other hand, using the proportional hazards model, necrosis was a significant predictor for recurrence (P = .02), as was the pair fibrosis and tumor detection when taken together (P = .05). Fibrosis significantly associated with high NG, Lagios' histological subtypes I and II, periductal lymphoid infiltrate, and necrosis (P < or = .0006).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗