Biomedical subjects

Nour Sneige

Publications and source records attributed to Nour Sneige.

At least 19 recordsLinked to original sources

PubMed2007

Adenovirus type 5 E1A gene therapy for ovarian clear cell carcinoma: a potential treatment strategy.

Resistance of ovarian clear cell carcinoma (CCC) to platinum-based chemotherapy is associated with poor prognosis, and an effective treatment for advanced disease is urgently needed. HER2/neu is up-regulated more often in CCC than in other histologic types of epithelial ovarian cancer. The purpose of this study was to assess possible treatment for ovarian CCC with the anti-HER2 antibody trastuzumab or human adenovirus type 5 E1A. We treated 10 CCC cell lines with trastuzumab or E1A and assessed cell viability, proliferation, and colony formation and the expression of HER2 and wild-type p53 proteins and molecules downstream of those signaling pathways. HER2 protein was detected at various levels in all 10 cell lines by Western blotting and in 5 CCC cell lines by immunohistochemical staining; HER2 gene amplification was detected (by fluorescence in situ hybridization) in only one cell line (RMG-I). Trastuzumab did not inhibit proliferation in any of the four CCC cell lines tested (RMG-I, SKOV-2, OVTOKO, and OVSAYO). However, transfection with E1A (as compared with control vectors) reduced colony formation in all 10 CCC cell lines regardless of HER2 expression level. Infection of RMG-I and SMOV-2 cells with an adenoviral vector encoding E1A led to significant (P < 0.05) suppression of proliferation and enhancement of cell death; this effect required stabilization of p53 (but not p73) protein and was associated with the up-regulation of Bax and the cleavage of caspase-9. Other mechanisms, such as p53-independent apoptosis, may also be involved in E1A-mediated cell death in CCC. Finally, treatment with E1A prolonged survival in a CCC xenograft model (P < 0.001). E1A gene therapy, because of its ability to stabilize wild-type p53, is worth exploring as a treatment modality for women with ovarian CCC, which typically expresses wild-type p53.

Adenocarcinoma, Clear Cell↗

PubMed2007

Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications.

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.

Adenoma, Sweat Gland↗

PubMed2006

Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma.

Current human papillomavirus (HPV) DNA testing using pooled probes, although sensitive, lacks specificity in predicting the risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV genotyping, viral load, and viral integration status as potential predictive markers for CIN progression, we performed HPV genotyping in formalin-fixed, paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened using consensus primers GP5+/GP6+ and PGMY09/11. HPV genotyping and viral load measurement were performed using quantitative real-time PCR for eight oncogenic HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA positivity increased in parallel with the severity of CINs and carcinoma, with 59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P trend=0.004). The eight oncogenic HPV types were significantly associated with CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval (CI), 5.67-39.76; P<0.0001) compared with the unknown HPV types (OR, 2.87; 95% CI, 0.89-9.22; P=0.08). HPV 16 was the predominant oncogenic HPV type in CIN 2/3 (51%) and carcinoma (71%) and integrated significantly more frequently in carcinoma than in CIN 2/3 (P=0.004). No significant differences in viral load were observed across the disease categories. Our findings suggest that selected genotyping for the eight oncogenic HPV types might be useful in separating women with a higher risk of CIN progression from those with a minimal risk. We also conclude that the HPV 16 integration status has potential to be a marker for risk assessment of CIN progression.

Adenocarcinoma↗

PubMed2006

Predictors of invasion in patients with core-needle biopsy-diagnosed ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy in ductal carcinoma in situ.

BACKGROUND: Among patients with core-needle biopsy (CNB)-diagnosed ductal carcinoma in situ (DCIS), the guidelines for the selection of patients to undergo sentinel lymph node (SLN) biopsy are not well defined, and many patients with no invasion undergo an unnecessary SLN biopsy. The objective of this study was to identify the predictors of invasion in patients with CNB-diagnosed DCIS and, thus, to help determine the most appropriate candidates for SLN biopsy. METHODS: The authors retrospectively evaluated 200 consecutive patients with CNB-diagnosed DCIS who underwent final excision at their institution between May 1, 2002 and June 30, 2005. Demographic data, the size and type of lesion on imaging studies, histologic features of DCIS on CNB, the number of cores taken, and the number of cores involved by DCIS were correlated with invasion on excision and SLN biopsy outcome. RESULTS: Forty-one of 200 patients (21%) had invasive carcinoma diagnosed on final excision. Parameters that correlated with invasion were a mass lesion, lesion size >1.5 cm, high nuclear grade, and the presence of lobular cancerization on CNB. A multivariate logistic regression model was developed to predict invasion. At the time of breast surgery, 103 of 200 patients (52%) underwent SLN biopsy, and 34 had invasion diagnosed on final excision. Three patients had 1 positive SLN each. CONCLUSIONS: A mass lesion, lesion size >1.5 cm, and the presence of lobular cancerization on CNB were significant, independent predictors of invasion in patients with DCIS. The authors recommended the inclusion of these predictors in the guidelines for selecting patients for SLN biopsy to reduce the number of unnecessary procedures.

Biopsy, Needle↗

PubMed2006

Fine-needle aspiration of pancreatic serous cystadenoma: cytologic features and diagnostic pitfalls.

BACKGROUND: The preoperative diagnosis of pancreatic serous cystadenoma (SCA) is important because as a typically benign tumor it can be treated expectantly, whereas many other cystic tumors require excision. This study examines the cytology, clinical and radiologic features, diagnostic accuracy of fine-needle aspiration (FNA), and potential pitfalls associated with this rare tumor. METHODS: Cytomorphologic features were retrospectively reviewed from 28 FNAs of SCA from 21 patients. FNA biopsies were guided by percutaneous computed tomographic or ultrasonographic imaging in 10 cases and by endoscopic ultrasonographic imaging in 18 cases. Corresponding histology (14 tumors) and clinical/imaging findings were also evaluated. RESULTS: Patients typically presented with upper abdominal discomfort or asymptomatically. Radiologically, a well-demarcated, multiloculated cystic mass involving the pancreatic head or uncinate process was common. Aspirates were sparsely cellular against a clean or granular, proteinaceous background. Tumor cells formed loose clusters or monolayered sheets composed of cuboidal cells with indistinct cell borders and granular or clear cytoplasm that was often stripped from the nucleus. Nuclei were small, round, with fine chromatin and indistinct nucleoli and devoid of mitotic activity. Seven (25%) of the aspirates were initially classified as "consistent with SCA," 6 (21%) as "no malignant cells," 3 (11%) as "nondiagnostic specimen," 3 (11%) as "suspicious for malignancy," 3 (11%) as "rare atypical cells," and 6 (21%) as "probably or consistent with mucinous cystic neoplasm." Features causing diagnostic difficulty were scant cellularity, papillary groups, nuclear atypia, and columnar cells mimicking those of mucinous neoplasms. Gastrointestinal (GI) epithelium and mucin also caused confusion. The detection of intracytoplasmic glycogen (3 of 6 cases) and cyst fluid analysis (2 of 2 cases) showing low viscosity and low or undetectable levels of carcinoembryonic antigen, CA 19.9, and amylase enhanced diagnostic confidence. CONCLUSIONS: Diagnosing SCA by FNA is challenging. Familiarity with its morphologic spectrum, use of ancillary studies, and correlation with clinical/radiologic findings greatly improves diagnostic accuracy. Contaminating GI epithelium and mucin should be distinguished from components of a mucinous neoplasm.

Adult↗

PubMed2006

Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer.

PURPOSE: We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases. PATIENTS AND METHODS: One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases. RESULTS: Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes + prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant. CONCLUSION: A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).

Adult↗

PubMed2006

The feasibility of gene expression profiling generated in fine-needle aspiration specimens from patients with follicular lymphoma and diffuse large B-cell lymphoma.

Lymphoma of germinal center cell (GC) origin generally is an indolent malignancy that transforms progressively into a more aggressive disease. According to the World Health Organization classification, lymphomas of follicular center cell origin are classified as either large B-cell lymphoma (LBCL) or follicular lymphoma (FL). The authors tested the feasibility of performing gene expression profiling using amplified RNA from fine-needle aspirates (FNA) obtained from lymph nodes. Twenty-four samples from patients with a diagnosis of FL or LBCL were obtained after Institutional Review Board-approved informed consent was obtained. The diagnoses were confirmed by 2 pathologists and were classified into 2 groups (10 LBCL samples and 14 FL samples) by using conventional morphology and immunophenotyping. One hundred nanograms of total RNA were subjected to 2 cycles of standard, double-stranded complementary DNA synthesis and in vitro transcription for target amplification using a small-sample target-labeling protocol. The biotinylated cRNA from each sample was hybridized to gene chips. Gene expression profiling results were analyzed first by principal-component analysis (PCA) by using a list of 146 probe sets that represented 62 genes that are characteristic of an activated B-cell (ABC) signature or a GC signature. The analysis identified 5 LBCL samples with an ABC cell signature. Using a list of 207 probe sets that represented 113 genes involved in FL transformation, PCA analysis identified 2 overlapping clusters corresponding to FL and GC-diffuse LBCL. To improve this classification further, the authors generated a list of 72 genes that were expressed differentially between FL and GC-LBCL. Using this list of genes, PCA analysis demonstrated a clear separation between FL and GC-LBCL. However, five FL samples clustered as an intermediate group between FL and GC-DLBCL. These samples were characterized morphologically by a mixed cell pattern with relatively fewer large, noncleaved lymphocytes and more small, cleaved lymphocytes. The results support the feasibility of FNA-based transcription profiles in patients with FL or LBCL, which, in combination with morphology and immunophenotyping, can help in the subtyping of these entities.

Biopsy, Fine-Needle↗

PubMed2006

Impact of concurrent proliferative high-risk lesions on the risk of ipsilateral breast carcinoma recurrence and contralateral breast carcinoma development in patients with ductal carcinoma in situ treated with breast-conserving therapy.

BACKGROUND: The purpose of the study was to determine the risk of ipsilateral breast carcinoma recurrence (IBCR) and contralateral breast carcinoma (CBC) development in patients with a concurrent diagnosis of ductal carcinoma in situ (DCIS) with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). METHODS: Records of all 307 patients with DCIS treated with breast-conserving treatment (BCT) from 1968 to 1998 were analyzed. Initial pathology reports and all slides available were re-reviewed for evidence of ADH, ALH, or LCIS. Actuarial local recurrence rates were calculated. RESULTS: Fifty-five cases of DCIS were associated with ADH, 11 with ALH or LCIS, and 14 with both ADH and ALH or LCIS. Overall, IBCR occurred in 14% and no significant difference in the IBCR rate was identified for patients with proliferative lesions compared with patients without these lesions (P = 0.38). Development of CBC in patients with concurrent DCIS and ADH was 4.4 times (95% confidence interval [CI], 1.44-13.63) that in patients with DCIS alone (P < 0.01). The 15-year cumulative rate of CBC development was 22.7% in patients with ALH or LCIS compared with 6.5% in patients without these lesions (P = 0.30) and 19% in patients with ADH compared with 4.1% in patients with DCIS alone (P < 0.01). CONCLUSION: The risk of CBC development is higher with concurrent ADH than in patients with DCIS alone, and these patients may therefore be appropriate candidates for additional chemoprevention strategies. Concurrent ADH, ALH, or LCIS with DCIS is not a contraindication to BCT.

Breast Neoplasms↗

PubMed2006

Sonographic and mammographic appearances of granular cell tumors of the breast with pathological correlation.

PURPOSE: To describe the sonographic and mammographic appearance of granular cell tumors (GCTs) of the breast in 6 patients with pathological correlation. METHODS: A search was conducted of the cyto-histopathological database in a single institution from 1990 to 2004 for breast lesions given the diagnosis of GCT of the breast. Six patients with GCT of the breast who underwent mammographic or sonographic examination or both before surgery were included in this study. RESULTS: The mammographic features of GCT of the breast were indeterminate in most patients, often presenting as an isodense mass with indistinct or spiculated margins. Calcifications were not a feature. The sonographic features of GCT of the breast mimicked carcinoma, including heterogeneous echotexture, indistinct margins, and hypervascularity. Hyperechogenicity was noted in 5 of 7 (71%) GCTs in this series. The cytomorphological features of GCT included sheets of large granular cells intersected by arborizing thin-walled blood vessels. The cells had round to oval nuclei, inconspicuous nucleoli, and abundant, ill-defined granular cytoplasm. CONCLUSIONS: Breast imagers should be aware that GCT of the breast is an uncommon differential in a minority of neoplasms that can be mistaken for breast cancer.

Adolescent↗

PubMed2006

Correlation of cytologic findings and chromosomal instability detected by fluorescence in situ hybridization in breast fine-needle aspiration specimens from women at high risk for breast cancer.

Cytologic evaluation of ductal lavage or random periareolar fine-needle aspiration (FNA) specimens has been proposed to improve risk stratification of women at high risk for breast cancer. However, cytologic assessment of morphologic changes is subjective. To assess the utility of fluorescence in situ hybridization (FISH) in the categorization of breast lesions, we prospectively evaluated 32 random periareolar FNA specimens from 27 women at high risk for breast cancer. Cytologic specimens were prepared using the thin preparation technique, and diagnoses were made on the basis of previously published criteria. Specimens were also evaluated by FISH for chromosomes 1, 8, 11, and 17. Monosomy was defined as the loss of one signal or both signals in >20% of cells, and polysomy was defined as the presence of > or = 3 signals in >6% of cells. Cytologic smears from seven invasive ductal carcinomas and nine benign breast specimens from women at low risk for breast cancer were included for comparison. In the high-risk group, cytologic findings were nonproliferative epithelium (NPE) in 16 cases and hyperplasia in 16 cases. Chromosomal aberrations were detected in 11 (69%) of 16 NPE cases, 14 (89%) of 16 hyperplasia cases, seven (100%) of seven carcinoma cases, and none of the low-risk cases. High-risk cases had significantly more monosomy of chromosomes 1, 11, and 17 and polysomy of chromosome 8 compared to low-risk cases and significantly less polysomy of chromosomes 1, 8, 11, and 17 compared to patients with cancer. There were no significant differences in monosomy or polysomy of individual chromosomes or a combination of chromosomes between the NPE and hyperplasia groups. This study shows that aberrations of chromosome number are common in high-risk women irrespective of cytologic findings. Studies evaluating the association between specific patterns of chromosomal polysomy and progression to malignancy may be warranted.

Adult↗

PubMed2006

Collagenous spherulosis of breast: morphologic study of 59 cases and review of the literature.

Collagenous spherulosis is a rare benign lesion that can microscopically mimic atypical ductal hyperplasia, cribriform ductal carcinoma in situ, or adenoid cystic carcinoma. Seventy-nine cases of collagenous spherulosis in women aged 36 to 90 years (mean age, 52 +/- 11 years) were identified from the University of Texas M. D. Anderson Cancer Center pathology files from the last 10 years. The pathology reports and slides from 59 patients were reviewed. This study does not attempt to evaluate the overall incidence of collagenous spherulosis because only cases with an actual diagnosis of collagenous spherulosis in pathology report were reviewed. The aim of this study was to investigate the underlying pathology within collagenous spherulosis and its relation to other pathologic findings within the specimen. Collagenous spherulosis was present as multiple foci ranging in size from 0.1 to 0.3 cm in 44 (75%) of the 59 cases. Collagenous spherulosis was associated with benign lesions of the breast in 41 cases, with atypical ductal hyperplasia in 3 cases, and with lobular carcinoma in situ in 15 cases. Microcalcifications were found in lesions involved by collagenous spherulosis in 15 cases. In summary, although collagenous spherulosis was mostly associated with benign breast lesions, in our study it was also frequently seen in association with lobular carcinoma in situ. Collagenous spherulosis could present as a mammographically suspicious mass or density and could be associated with microcalcifications. Increased numbers of cases of collagenous spherulosis may be expected in the future as a result of breast cancer-screening programs. Caution is needed not to overinterpret collagenous spherulosis as atypical or ductal carcinoma in situ, especially on core needle biopsy specimens.

Aged↗

PubMed2006

Fine-needle aspiration of adrenal cortical carcinoma: cytologic spectrum and diagnostic challenges.

We reviewed the cytologic features of 20 adrenal cortical carcinomas (ACCs; 9 primary and 11 metastatic) from 19 patients and highlighted diagnostic pitfalls. The mean size of primary ACCs was 11.9 cm, and that of metastatic ACCs was 3.0 cm. The metastatic sites were liver, lung, lymph node, soft tissue, and bone. Primary and metastatic ACCs were cytologically similar and showed a wide range of features varying from well-differentiated tumor resembling a benign cortical lesion or low-grade neuroendocrine tumor to poorly differentiated pleomorphic tumor mimicking poorly differentiated carcinoma, melanoma, or high-grade sarcoma. The common cytologic features were hypercellularity (70% of cases), necrotic debris in the background (70%), moderate to marked nuclear pleomorphism (80%), mitotic figures (90%), and prominent nucleoli (60%). Twenty percent of cases exhibited all 5 features; 40% exhibited 4 features, and 40% exhibited 3 features. Necrosis and/or mitosis were found in all cases, even in tumors with bland cytologic features. Cytologic, immunophenotypic, and ultrastructural findings should be correlated with clinical and radiologic information for achieving a proper cytologic diagnosis.

Adolescent↗

PubMed2006

Downregulation of the cyclin-dependent kinase inhibitor p27kip1 might correlate with poor disease-free and overall survival in inflammatory breast cancer.

PURPOSE: The objective of this study was to evaluate whether p27kip1 downregulation is a prognostic factor in patients with inflammatory breast carcinoma (IBC). PATIENTS AND METHODS: Fifty-eight patients with IBC were treated between January 1994 and July 2002. Median age was 49 years. Thirty-eight patients had baseline biopsy specimens. Patients received preoperative chemotherapy with FAC (5-fluorouracil/doxorubicin/cyclophosphamide; 34%) or FAC followed by a taxane (66%). All patients underwent mastectomies. All patients received radiation therapy and hormonal treatment when indicated. Expression level of p27kip1 was evaluated by indirect immunoperoxidase procedure. The p27kip1 was considered downregulated if nuclear staining was present in < 50% of the neoplastic cells. RESULTS: Thirty-two patients (84%) had p27kip1-downregulated tumors, and 6 patients (17%) had p27kip1-normal tumors. Six patients (16%) exhibited a pathologic complete response. At a median follow-up of 43 months, 25 recurrences (66%) and 27 deaths (71%) occurred. Patients with p27kip1-downregulated tumors had fewer pathologic complete responses (9% vs. 50%; P = 0.03) and had lower 4-year recurrence-free survival (23% vs. 83%; P = 0.03) and overall survival rates (36% vs. 83%; P = 0.01). CONCLUSION: The p27kip1 deregulation manifested by low protein cellular concentration might represent an adverse prognostic marker in IBC and could provide a valuable tool for selecting treatment for this aggressive disease.

Adult↗

PubMed2006

Transthoracic fine-needle aspiration vs concurrent core needle biopsy in diagnosis of intrathoracic lesions: a retrospective comparison of diagnostic accuracy.

To assess the value and limitations of fine-needle aspiration (FNA) and core needle biopsy (CNB) in the diagnosis of intrathoracic lesions, we retrospectively compared the diagnostic accuracy of 362 FNA and concurrent CNB procedures performed on 350 patients. Based on the final diagnoses that were determined based on combined information from biopsy, resection, clinical, radiologic, and microbiologic findings, the study cases were grouped into 188 malignant, 161 benign, and 13 inconclusive lesions. FNA and CNB yielded similar diagnostic accuracy for malignant tumors (85.1% vs 86.7%) and epithelial malignant neoplasms (86.4% vs 85.2%), whereas CNB yielded better diagnostic accuracy (96%) than FNA (77%) for nonepithelial malignant neoplasms. Combined FNA and CNB substantially improved the rate of malignancy diagnosis (95.2%). Of 161 benign cases, 50 were proven to be benign-specific lesions; FNA provided specific diagnosis in 20 (40%) and CNB in 46 (92%). The remaining 111 benign lesions yielded benign-nonspecific findings on both specimens. These results indicate that CNB should be obtained when clinical or radiologic findings do not match the cytologic findings or nonepithelial lesions and benign lesions are considered likely.

Adolescent↗

PubMed2005

Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy.

PURPOSE: Pathologic complete remission (pCR) of primary breast tumors after primary chemotherapy (PCT) is associated with higher relapse-free survival (RFS) and overall survival (OS) rates. The purpose of this study was to determine long-term outcome in patients achieving pCR of cytologically proven axillary lymph node (ALN) metastases. METHODS: Patients with cytologically documented ALN metastases were treated in five prospective PCT trials. After surgery, patients were subdivided into those with and without residual ALN carcinoma. Survival was calculated by the Kaplan-Meier method. RESULTS: Of 925 patients treated, 403 patients had cytologically confirmed ALN metastases. Eighty-nine patients (22%) achieved ALN pCR after PCT. Compared with the group without ALN pCR, 5-year OS and RFS were improved in patients achieving ALN pCR (93% [95% CI, 87.5 to 98.5] and 87% [95% CI, 79.7 to 94.3] v 72% [95% CI, 66.5 to 77.5] and 60% [95% CI, 54.1 to 65.9], respectively; P < .0001). Residual primary tumor did not affect outcome of those with ALN pCR. Combination anthracycline/taxane-based PCT resulted in significantly more ALN pCRs, although outcome after ALN pCR was not improved by taxanes. We constructed a nomogram demonstrating that patients who do not benefit from neoadjuvant anthracyclines are unlikely to benefit from subsequent taxanes. CONCLUSION: ALN pCR is associated with an excellent prognosis, even with a residual primary tumor, pointing to biologic differences between primary and metastatic cells. ALN pCR represents an early surrogate marker of long-term outcome. Response to initial PCT has important potential as a guide to subsequent therapy.

Adult↗

PubMed2005

Validation of commonly used immunostains on cell-transferred cytologic specimens.

BACKGROUND: Immunocytochemical staining (ICC) is often limited by the lack of cell blocks that contain diagnostic cells or by the unavailability of smear materials. The cell-transfer technique, in which original smear material is divided into several pieces and then transferred to multiple slides, can facilitate multiple ICC on limited materials. However the reliability of the staining results has not been systematically evaluated. METHODS: The authors validated 21 commonly used antibodies (cytokeratin [CK] 7, CK 20, TTF-1, panCK, vimentin, HMB-45, Mart-1, leukocyte common antigen, chromogranin, synaptophysin, estrogen receptor, progesterone receptor, prostate-specific antigen, prostatic acid phosphatase, calretinin, CK5/6, WT-1, BerEP4, MOC-31, p63, and thyroglobulin) on the cell-transferred materials of various tumor samples (n = 20) and reactive effusion samples (n = 2). The staining results were compared with the previously available ICC results (performed either on cell block sections or on smears) of the same specimens. RESULTS: One hundred pieces of transferred materials were immunostained, of which 5 (5%) were lost during the staining procedure. Of the remaining 95 pieces, 92 (97%) showed staining results that agreed with those of the previous ICC, whereas 3 (3%) showed results that disagreed. The original ICC in the latter three specimens was performed on cell block sections and showed focally positive synaptophysin staining in a sample with a neuroendocrine tumor, focally positive CK5/6 staining in a pleural effusion sample with mesothelioma, and positive TTF-1 staining in a lymph node sample with metastatic lung carcinoma. Their corresponding ICC of cell-transferred materials showed negative results. An increase in background staining was observed in 1 of the 95 tissue pieces, but no false-positive results were observed. CONCLUSIONS: In general, ICC can be reliably performed on cell-transferred tissue specimens for markers tested. However, caution should be taken when interpreting ICC results in tissue specimens with limited cellularity and heavy background staining.

Biopsy, Needle↗

PubMed2005

Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma.

BACKGROUND: Accurate assessment of HER-2 status is necessary prior to anti-HER-2 antibody (trastuzumab) therapy for metastatic breast carcinoma. However, controversy exists regarding whether to assess HER-2 status in the primary tumor or in metastatic lesions. It is also unclear whether HER-2 status can change during disease progression or after chemotherapy. METHODS: Breast carcinoma samples from 60 women with known HER-2 status in both primary tumors and paired metastases (locoregional disease, n = 43 patients; distant disease, n = 17 patients) were reviewed retrospectively. Thirty-two patients underwent chemotherapy before their metastatic lesions were sampled, including 18 patients who received neoadjuvant chemotherapy and 14 patients who received adjuvant chemotherapy. The HER-2 gene was examined by fluorescence in situ hybridization either in paraffin-embedded tissue samples (48 primary tumors and 9 metastatic tumors) or in fine-needle aspirates (12 primary tumors and 51 metastatic tumors). HER-2 gene amplification was defined as a HER-2:chromosome 17 signal ratio >/= 2.0. RESULTS: The HER-2 status of primary and metastatic tumors agreed in 58 of 60 patients (97%), including 18 (30%) amplified tumors and 40 (67%) nonamplified tumors. A discrepancy in HER-2 status was observed in specimens from two patients in which HER-2 amplification was detected in the primary tumor but not the metastatic tumors. In one patient, three foci of tumor nodules were found in the same breast; the HER-2 status was assessed in only one of them, which showed amplification; however, HER-2 amplification was not detected in the axillary lymph node metastasis. In another patient, the HER-2 gene was amplified in the primary tumor but not in the liver metastasis. No metastases showed HER-2 amplification without amplification in the primary tumor. Locoregional and distant metastases demonstrated similar concordance rates with their corresponding primary tumors (98% and 94%, respectively). Complete concordance of HER-2 status was found between primary tumors prior to chemotherapy and metastases that were sampled after chemotherapy. CONCLUSIONS: The HER-2 status in breast carcinoma generally was stable during metastasis, whether to locoregional or distant sites. Chemotherapy did not modify the HER-2 status in metastatic lesions. Therefore, HER-2 amplification can be evaluated reliably in material from either primary or metastatic tumors in most patients. Further study with larger series is warranted to elucidate the significance of discordant results.

Adult↗

PubMed2005

CD44 expression is associated with increased survival in node-negative invasive breast carcinoma.

PURPOSE: CD44 is a multifunctional cell surface receptor with many known splice variants, some of which have been reported to play a role in tumor progression. The purpose of this study was to evaluate the prognostic significance of CD44 isoforms in early-stage, lymph node-negative invasive breast carcinoma. EXPERIMENTAL DESIGN: Immunohistochemical staining for CD44 isoforms was done on archival paraffin tissue sections of invasive breast carcinoma from a cohort of lymph node-negative patients who received no adjuvant tamoxifen or chemotherapy and who had a mean clinical follow-up period of 15 years. Immunohistochemical staining was done with antibodies to CD44s, the standard isoform of CD44, and to isoforms containing variant exon 6 (CD44v6); levels of staining were correlated with clinical outcome data. RESULTS: There was a trend towards increased disease-free survival for patients whose tumors had high anti-CD44s positivity (P = 0.05), and a significant association was observed between anti-CD44s positivity and disease-related survival (P = 0.04). Expression of CD44v6 isoforms did not correlate with clinical outcome. CONCLUSION: CD44 expression, as assessed by immunohistochemical staining with anti-CD44s, may be a favorable prognostic factor in patients with node-negative invasive breast carcinoma.

Adult↗