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Mehrdad Nadji

Publications and source records attributed to Mehrdad Nadji.

18 recordsLinked to original sources
PubMed2006

Detection of tumor cells in body cavity fluids by flow cytometric and immunocytochemical analysis.

Measurement of electronic volume versus DNA content of nuclei can be used to discriminate between normal and malignant cells. Epithelial membrane antigen immunocytochemistry (EMA-ICC), a helpful ancillary test in body cavity fluids, is not universally accurate for detecting malignancy in effusions. The current study was undertaken to determine if multiparametric flow cytometry (based on simultaneous analysis of light scatter, nuclear volume, DNA, and nuclear protein content) in combination with (EMA-ICC) could be used for the detection of malignant cells in peritoneal and pleural fluids. We studied 130 body cavity fluids (68 peritoneal and 62 pleural fluids) by conventional cytology and multiparametric laser flow cytometry. EMA-ICC was performed using EMA antibodies and L-SAB detection system (DakoCytomation, Carpinteria, CA). EMA-ICC had significantly higher sensitivity than conventional cytology (79% versus 59%, P = 0.016) and ploidy (79% versus 38%, P = 0.001). Cytology had significantly higher specificity than ploidy (97% versus 82%, P = 0.012). The differences in specificity between EMA-ICC and ploidy (87% versus 82%, P= 0.607) or EMA-ICC and cytology (87% versus 97%, P = 0.109) were not statistically significant. However, assuming serial testing, sensitivity increased significantly for the combinations of cytology and EMA-ICC (79.4%, P = 0.016) and cytology and ploidy (73.5%, P = 0.004) as compared to cytology alone (58.8%). Also, the combination of cytology and ploidy had a higher sensitivity than ploidy alone (73% versus 38%, P < 0.0001). However, the sensitivity associated with the three tests used in serial (85.3%) was not significantly different from the sensitivities corresponding to the combination of cytology and EMA-ICC (79%) or cytology and ploidy (73%). Multiparametric flow cytometry utilizing high resolution DNA, nuclear volume, protein measurement, and ICC, in combination with cytomorphology, may be a valuable tool for rapid identification of malignant cells in body cavity fluids.

Aneuploidy↗
PubMed2006

Tissue detection of biomolecular predictors in breast cancer.

One of the promises of modern biotechnology is to improve medical care by providing accurate diagnosis and targeted treatment to patients who will derive the maximum benefit. Delivery of this promise in the 21st century is the result of major advances in biotechnology over the past 20 years. Sequencing of the human genome and other high-volume data discovery has become possible, owing to relatively inexpensive computation power and automation. The same forces that drove the human genome project are now being focused on cataloging various disease processes at the DNA, RNA and protein levels. As these high-throughput technologies are entering the clinical care environment, the major task at hand is to integrate the complex data and derive clinically useful information. In spite of major breakthroughs in molecular approaches to the diagnosis and prognostication of cancer, there remain significant obstacles in applying these technologies to clinical samples. The time-honored conventional histopathology, for example, is still the backbone of tumor diagnosis and prognostication. The traditional fixation and processing methods are, however, rapidly losing ground, as they do not protect important tissue macromolecules. Formalin, the common universal fixative, is losing its place in histopathology. In addition to its toxicity, it alters macromolecules and renders the tissue unfit for most advanced molecular studies. This has prompted the use of fresh or fresh-frozen biopsy material for most biomolecular discoveries and clinical assays. This of course is impractical, or even impossible, in most clinical settings, particularly since tumors are being detected earlier and smaller. Also, many preneoplastic conditions are impossible to triage for freezing since their accurate diagnosis requires the use of the entire sample for detailed microscopic examination. The focus in this report is on breast cancer, where the value of the innovative approaches of the tissue detection of biomolecular predictors is examined. To this end, novel tissue handling platforms are introduced that are not only suitable for histological diagnosis, but allow the detection of tumor proteome and expression profiles on the same biopsy sample.

BRCA2 Protein↗
PubMed2006

High proliferative activity excludes dermatofibroma: report of the utility of MIB-1 in the differential diagnosis of selected fibrohistiocytic tumors.

CONTEXT: Dermatofibroma is a benign fibrohistiocytic tumor composed of a mixture of fibroblastic and histiocytic cells. The diagnosis of this tumor is generally uncomplicated; however, rare variants may be difficult to distinguish from malignant fibrohistiocytic tumors. Deep penetrating dermatofibroma may be difficult to distinguish from dermatofibrosarcoma protuberans, and pseudosarcomatous dermatofibroma and dermatofibroma with monster giant cells share morphologic similarities with malignant fibrous histiocytoma and atypical fibroxanthoma. OBJECTIVE: To find an immunohistochemical marker or markers that differentiate between fibrohistiocytic lesions of skin. DESIGN: We evaluated the immunophenotypic characteristics of 83 fibrohistiocytic tumors (36 typical dermatofibromas, 16 cases of dermatofibrosarcoma protuberans, 16 malignant fibrous histiocytomas, and 15 atypical fibroxanthomas) using antibodies against MIB-1 (Ki-67), factor XIIIa, CD34 (HPCA-1), HHF35 (muscle-specific actin), 1A4 (smooth muscle actin), cytokeratin (AE1/AE3, CAM 5.2, and 34betaE12), S100 protein, and desmin. RESULTS: A high proliferative index detected by MIB-1 staining excluded the possibility of dermatofibroma and was diagnostically useful in separating this entity from dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, and atypical fibroxanthoma. A low proliferative index, however, could not differentiate dermatofibroma from dermatofibrosarcoma protuberans. Factor XIIIa reactivity was not helpful for the diagnosis of dermatofibroma, whereas CD34 reactivity was statistically significant in the diagnosis of dermatofibrosarcoma protuberans. The sensitivity of these 2 markers is low and therefore of questionable practical diagnostic value. CONCLUSION: Evaluation of the proliferative index may further assist in distinguishing dermatofibroma from dermatofibrosarcoma protuberans, atypical fibroxanthoma, and malignant fibrous histiocytoma.

Biomarkers, Tumor↗
PubMed2005

Methodology for preservation of high molecular-weight RNA in paraffin-embedded tissue: application for laser-capture microdissection.

Laser-capture microdissection techniques have enhanced the ability to perform molecular studies of pure-cell populations. Although many technical factors affect the outcome of the procedure, none is more critical than the appropriate handling of the tissue. Because extraction of intact RNA from paraffin-embedded tissue is a difficult and inconsistent process, frozen sections with their attendant problems are used for this purpose. The major limitation of frozen section is its inferior morphologic quality compared with paraffin-embedded sections that may complicate accurate identification of cells during microdissection. We have developed a procedure that provides both high-quality histomorphology and RNA preservation in paraffin-embedded tissue. It is based on the use of a methanol-based fixative coupled with microwave-assisted rapid tissue processing. This technology in conjunction with a modified hematoxylin-eosin stain and a RNA extraction method allows isolation of high molecular-weight RNA from laser-capture microdissected, hematoxylin and eosin-stained paraffin sections. The high quality of the extracted RNA was confirmed by capillary electrophoresis and RT-PCR. The combination of a methanol-based fixative, rapid microwave tissue processing, and a modified hematoxylin and eosin stain produces paraffin sections that yield high molecular-weight RNA upon microdissection. This methodology opens the door for a wide range of gene expression analyses using paraffin-embedded tissue.

Electrophoresis, Capillary↗
PubMed2005

Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers.

Paraffin sections or fine-needle aspiration smears from 5,993 cases of invasive mammary carcinomas were assessed immunohistochemically for estrogen receptor (ER; 1D5) and progesterone receptor (PR; 636) expression. Staining pattern and intensity were correlated with histologic subtypes and nuclear grades of tumors. Positive nuclear staining for ER and PR was observed in 75% and 55% of invasive carcinomas, respectively. In 92% of ER+ cases, diffuse and uniform staining of most tumor cells was observed. In the remaining 8%, a focal ER reaction was seen, usually because of inadequate fixation. In 21% of PR+ tumors, the reaction was heterogeneous or focal but unrelated to fixation. There were no ER-, PR+ tumors. All pure tubular, colloid, and infiltrating lobular carcinomas were ER+. All medullary, apocrine, and metaplastic and most high-nuclear-grade carcinomas were ER-. With monoclonal antibody 1D5 and antigen retrieval, immunohistochemical reaction for ER in breast cancer usually is an all-or-none phenomenon; therefore, quantitation of results is unnecessary. Despite antigen retrieval, inadequate fixation can cause false-negative results; evaluation of internal positive control samples is imperative. ER positivity and negativity are predictable in certain histologic types and nuclear grades of breast cancer. The reaction for PR can be heterogeneous or focal.

Breast Neoplasms↗
PubMed2004

Androgen and vitamin D receptor expression in archival human breast tumors.

BACKGROUND: The present study was undertaken for quantitation of androgen (AR) and vitamin D (VDR) receptor expression in human male and female breast tumors by flow cytometry. METHODS: Nuclei isolated from sections of paraffin-embedded tumors by pepsin digestion were treated for antigen unmasking and incubated with antibodies to AR and VDR. Flow cytometric analysis was used to determine the percentage of receptor-positive nuclei with fluorescence greater than 95% of the isotype nuclei. Mean log fluorescence channel values were used for comparing antigen density of the isotype and the antibody-treated nuclei. RESULTS: Six of 23 female breast tumors had aneuploid DNA content. Nineteen of 20 estrogen receptor-positive female tumors by immunohistochemical analysis (IHC) were also AR positive by flow analysis. Aneuploid subpopulations had higher percentages of AR-positive nuclei than did diploid populations. Eight of 33 male breast tumors had aneuploid DNA content. Twenty-three of 33 male breast tumors were AR positive by flow analysis compared with six that were AR positive by IHC. Six AR-positive (IHC) male tumors were also AR positive by flow analysis. VDR expression was higher in diploid female tumors than in aneuploid tumors. CONCLUSIONS: Lack of a strong correlation between IHC and flow analysis may be due to differences in criteria used for identification of receptor-positive and -negative tumors by the two methods.

Aneuploidy↗
PubMed2004

Experience with an automated microwave-assisted rapid tissue processing method: validation of histologic quality and impact on the timeliness of diagnostic surgical pathology.

We studied the effect of a fully automated microwave-assisted rapid tissue processor (RTP) on histologic examination and on the turnaround time for surgical pathology reports. A quality assurance program reviewed the histologic sections obtained by the rapid processing method for the last 3 calendar years. In addition, the histologic results from this method were compared blindly with those obtained from the conventional overnight tissue processing (CTP) method by 9 pathologists with different levels of experience. The surgical pathology turnaround times for 1 year of use of the RTP were compared with the last year for CTP. We found that the RTP reproducibly yielded histologic material comparable in quality to CTP. The turnaround time for surgical pathology reports was improved substantially, and, in particular, same-day reporting was achieved in approximately 55% of cases compared with fewer than 1% before use of the RTP. Moreover, use of the RTP enhanced safety by eliminating formalin and xylene from the procedure.

Humans↗
PubMed2003

Papillary squamous cell carcinoma of the uterine cervix: an immunophenotypic appraisal of 12 cases.

OBJECTIVE: The objective was to evaluate the role of human papillomavirus (HPV) in the pathogenesis of papillary squamous cell carcinoma (PSCC) of the cervix and to determine cell proliferative activity and p53 abnormalities in these rare variants of cervical cancer. METHODS: Twelve examples of PSCC of the cervix were diagnosed between 1990 and 1999. Formalin-fixed paraffin sections of each tumor were stained by immunoperoxidase method using antibodies to p53 gene product (CM-10) and Ki-67 (MIB-1). In situ hybridization for HPV DNA (ENZO) was used to detect specific sequences of DNA shared by most types of genital HPV, followed by confirmatory PCR analysis. The nuclear staining for Ki-67 was graded as minimal (<10% of cells), moderate (between 10 and 50% of cells), and high (>50% of cells). RESULTS: Fifty-percent of the tumors showed presence of HPV DNA. Three tumors (25%) showed nuclear accumulation of p53. Moderate and high proliferative activity was observed in four and eight of tumors, respectively. Eight patients presented with stage IB1 tumor (67%), 3 with stage IA1 tumor (25%), and 1 with stage IIIA tumor (8%). Eleven patients (92%) were alive as of last contact with a mean follow-up of 34.2 months (range: 5 days to 84 months). CONCLUSION: In this series of patient, PSCC of the uterine cervix had a low rate of HPV DNA in their genome and a low rate of p53 gene abnormality. These genotypic differences may explain the differences between the clinical behavior of PSCC and the common types of squamous cell carcinomas of the cervix.

Adult↗
PubMed2003

Renal cell carcinoma antigen is expressed by yolk sac tumors and yolk sac elements of embryonal carcinomas.

Renal cell carcinoma antigen is a rather specific marker for normal and neoplastic renal tissue. We investigated the expression of this antigen in 34 gonadal and extragonadal germ cell tumors, including 8 pure yolk sac carcinomas and 26 embryonal carcinomas, 15 of which were combined with teratomas, seminomas, and dysgerminomas. Renal cell carcinoma antigen was demonstrated in all 8 yolk sac tumors and 21 of 26 embryonal carcinomas (81%). In yolk sac tumors, renal cell carcinoma antigen reactivity was diffusely present throughout the tumors. In embryonal carcinomas, this marker was identified only in yolk sac components. Both intracytoplasmic and membranous staining patterns were present. No reactivity was noticed in embryonal carcinoma cells, seminoma, dysgerminoma, and other components of teratomas. The study suggests an antigenic similarity between renal tubules and yolk sac tumors. Furthermore, the renal cell carcinoma antigen may be used as an addition to the panel of immunocytochemical markers for yolk sac carcinomas.

Adolescent↗
PubMed2003

Melan A (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas.

Most adrenocortical neoplasms, renal cell carcinomas, and hepatocellular carcinomas are diagnosed by a combination of clinical and morphologic features. However, occasionally this histologic differential diagnosis requires additional ancillary tests, such as immunohistochemistry. The authors investigated the potential value of A103 in the differential diagnosis of these tumors. Thirty-two adrenocortical neoplasms, 86 renal cell carcinomas, and 57 hepatocellular carcinomas were evaluated by immunohistochemistry using a monoclonal antibody A103 and a standard ABC method. The adrenocortical neoplasms were 21 adenomas and 11 carcinomas. Thirty-one of the 32 adrenocortical neoplasms showed strong and diffuse granular cytoplasmic staining for Melan A. No nuclear reaction was observed. There were no differences in staining patterns between adrenocortical adenomas and carcinomas. With the exception of one clear cell renal cell carcinoma, all non-adrenocortical neoplasms were negative. The authors conclude that A103 is a useful addition to the immunohistochemical panel in the differential diagnosis of adrenocortical neoplasms from both renal cell and hepatocellular carcinomas. This marker, however, does not separate benign from malignant adrenocortical neoplasms.

Adrenal Cortex Neoplasms↗
PubMed2003

A tissue fixative that protects macromolecules (DNA, RNA, and protein) and histomorphology in clinical samples.

Preservation of macromolecules (DNA, RNA, and proteins) in tissue is traditionally achieved by immediate freezing of the sample. Although isolation of PCR-able RNA has been reported from formalin-fixed, paraffin-embedded tissues, the process has not been shown to be reproducible because high molecular weight RNA is usually degraded. We investigated the potential value of a new universal molecular fixative (UMFIX, Sakura Finetek USA, Inc., Torrance, California) in preservation of macromolecules in paraffin-embedded tissue. Mouse and human tissues were fixed in UMFIX from 1 hour to 8 weeks. They were then processed by a rapid tissue processing (RTP) system, embedded in paraffin, and evaluated for routine histology as well as for the quality and quantity of DNA, RNA, and proteins. Formalin-fixed tissues were processed by RTP and evaluated in a similar manner. Fresh-frozen samples were used as controls. The morphology of UMFIX-exposed tissue was comparable to that fixed in formalin. High molecular weight RNA was preserved in tissue that was immediately fixed in UMFIX and stored from 1 hour to 8 weeks at room temperature. There were no significant differences between UMFIX-exposed and frozen tissues on PCR, RT-PCR, real-time PCR, and expression microarrays. Similarly, physical and antigenic preservation of proteins in UMFIX tissue was similar to fresh state. Both RNA and proteins were substantially degraded in formalin-fixed and similarly processed specimens. We concluded that it is now possible to preserve histomorphology and intact macromolecules in the same archival paraffin-embedded tissue through the use of a novel fixative and a rapid processing system.

Animals↗
PubMed2003

Low nuclear proliferative activity is associated with nonmetastatic islet cell tumors.

CONTEXT: Traditional morphologic features of tumor aggression are of limited value in predicting the malignant behavior of endocrine neoplasms. We explored the potential value of nuclear proliferative activity (using Ki-67 immunostaining with semiquantitative scoring) in predicting the clinical behavior of pancreatic islet cell tumors (ICTs), and we correlated this characteristic with hormone expression. OBJECTIVE: To evaluate whether Ki-67 immunostaining using a semiquantitative scoring system has value in predicting the clinical behavior of pancreatic ICTs. DESIGN: We studied 39 pancreatic ICTs from 39 patients. Twenty-two ICTs did not metastasize in a median follow-up period of 91 months. The remaining 17 neoplasms did produce metastases (8 in liver, 7 in regional lymph nodes, and 2 in peritoneum). Immunohistochemistry was performed using antibodies to Ki-67 and pancreatic hormones (insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, and corticotropin). A semiquantitative Ki-67 grading system was followed. The nuclear proliferative activity, as determined by a positive reaction for Ki-67, was considered low (<5% of cells staining positively), intermediate (5%-25% of cells staining positively), or high (>25% of cells staining positively). RESULTS: The majority of the nonmetastatic ICTs (16 cases, 73%) demonstrated either negative or low staining for Ki-67 (P <.001). Conversely, all metastatic ICTs expressed at least an intermediate-grade reaction. High nuclear proliferative activity was only seen in metastatic neoplasms (3 cases, 17%). There was no relationship between immunoexpression of pancreatic hormones and nuclear proliferative activity by either group of tumors. CONCLUSION: An ICT with low nuclear proliferative activity is unlikely to metastasize, whereas high proliferative activity is associated with a metastatic phenotype. Immunohistochemical assessment of Ki-67 using a semiquantitative scoring system is a simple and reliable detection method of cellular proliferative activity in ICTs of the pancreas.

Adult↗
PubMed2002

Expression of glucose transporter-1 in cervical cancer and its precursors.

OBJECTIVE: Increased glucose uptake and utilization is a known phenomenon exhibited by malignant cells. Overexpression of the glucose transporter protein family is thought to be the principal mechanism by which these cells achieve up-regulation. Our purpose is to determine glucose transporter-1 (GLUT 1) expression in squamous carcinoma of the cervix and precursor lesions. METHODS: Archival histologic sections were obtained from 31 cases of invasive squamous cell carcinoma (SCC) of the uterine cervix, 15 cases of high-grade cervical intraepithelial neoplasia, 5 cases of low-grade, and 9 normal cervices. Immunohistochemistry for GLUT 1 protein was performed using polyclonal GLUT 1 antibody (Dako, Carpinteria, CA) and the labeled streptavidin-biotin procedure. RESULTS: Compared to the internal control, the pattern of staining varied from weak (1+) to strong (3+) reactions. In normal cervix, 1+ GLUT 1 staining was seen in the basal cells of the squamous epithelium. All 31 (100%) cases of SCC were positive for GLUT 1. Positive reactions seemed more intense in tumor cells that were farther away from the stromal blood supply. There was a correlation between intensity of reaction for GLUT 1 and histologic grade of tumor (P = 0.0027) and with progression from normal or dysplastic lesions to invasive cancer (P = 0.0001). Intensity was a predictor of the presence of poorly differentiated tumor type. Low-grade CIN staining was seen in less than one-third of the epithelium, while in high-grade lesions the reaction was present in over one-half of the epithelium. CONCLUSIONS: GLUT 1 is overexpressed in cervical carcinoma. The process appears to be related to grade of tumor but not to the progression from preneoplastic lesions. The results suggest that GLUT 1 overexpression is a late phenomenon in cellular transformation. Furthermore, the possible relation of expression to tumor blood supply suggests that the malignant cells may have an adaptive environmental ability to compensate for a compromised microenvironment.

Adult↗
PubMed2002

Calretinin and inhibin are useful in separating adrenocortical neoplasms from pheochromocytomas.

Most adrenocortical neoplasms and pheochromocytomas can be diagnosed by a combination of clinical findings and morphologic features. Occasionally, however, this histologic differential diagnosis requires ancillary tests, such as immunohistochemistry. Both tumors are generally negative for epithelial markers but express synaptophysin. Inhibin and chromogranin are used for the diagnosis of adrenocortical neoplasms and pheochromocytomas, respectively. Both antigens, however, are expressed focally and may be completely negative, particularly in small biopsies. The authors investigated the potential value of adding calretinin to inhibin in the differential diagnosis of these tumors. Fifty-five primary adrenal neoplasms including 33 adrenocortical tumors (21 adenomas and 12 carcinomas), 22 pheochromocytomas, and 7 healthy adrenal glands were examined immunohistochemically for the expression of calretinin and inhibin. Inhibin was demonstrated in 24 (73%) adrenocortical neoplasms. When calretinin was added, the number of tumors staining positively for the two markers alone or in combination increased to 31 (94%). Both antigens showed a focal pattern of distribution in many cases. None of the pheochromocytomas reacted for any of these two markers. Healthy adrenal gland showed a distinct positive and negative pattern of immunoreactivity for both antigens in cortex and medulla, respectively. There were no differences between staining patterns of calretinin and inhibin in healthy adrenal cortex, adrenocortical adenomas, and adrenocortical carcinomas. The authors conclude that the addition of calretinin to inhibin increases the sensitivity of the diagnosis of adrenocortical neoplasms. When used together, they are highly specific and sensitive for the differential diagnosis of these tumors from pheochromocytomas. These markers, however, do not distinguish between benign and malignant adrenocortical neoplasms.

Adrenal Cortex Neoplasms↗
PubMed2002

Her2 expression in prostatic cancer: a comparison with mammary carcinoma.

PURPOSE: There is growing interest in HER2 and its downstream signaling pathway molecules as treatment targets in human malignancies, including prostatic carcinoma. We used a standard Food and Drug Administration approved HER2 immunohistochemical kit to study HER2 expression in prostate cancer. We compared the results with those reported for mammary carcinoma. MATERIALS AND METHODS: For this study we selected 216 specimens obtained from patients who underwent radical prostatectomy for primary untreated prostatic carcinoma. Immunohistochemical staining was performed using the HercepTest kit (Dako Corp., Carpinteria, California) in strict fashion according to the technical and analytical protocols outlined in the kit. RESULTS: Of the tumors 33 (15%) were positive for HER2, including 31 (94%) that were only weakly positive (2+). Of the HER2 positive tumors 97% were Gleason grade 7 or higher. Of the 33 positive cases 22 (67%) showed only a focal positive reaction for HER2 in discrete tumor areas. CONCLUSIONS: HER2 is expressed in a minority of untreated primary prostatic carcinomas. Unlike in mammary carcinoma, HER2 positivity in prostatic cancer is usually weak in intensity and focal in distribution. While the former casts doubt on the usefulness of HER2 as a potential treatment target for most primary untreated prostatic cancer, the latter phenomenon may lead to false-negative results if the test is performed in small biopsies. Furthermore, HER2 staining of prostatic carcinoma can be technically and analytically reproducible provided that there is strict adherence to the outlined methodologies and interpretation.

Adenocarcinoma↗
PubMed2002

Continuous-specimen-flow, high-throughput, 1-hour tissue processing. A system for rapid diagnostic tissue preparation.

CONTEXT: Current conventional tissue-processing methods employ fixation of tissues with neutral buffered formalin, dehydration with alcohol, and clearing with xylene before paraffin impregnation. Because the time required for this procedure is usually 8 hours or longer, it is customary to process tissues in automated instruments throughout the night. Although this time-honored method continues to serve histology laboratories well, it has a number of shortcomings, such as a 1-day delay of diagnosis, the need to batch specimens, the relatively large volumes and toxicity of reagents used, and the extent of RNA degradation. OBJECTIVE: To describe a rapid new method of tissue processing using a continuous-throughput technique. Design.-We used a combination of common histologic reagents, excluding formalin and xylene, as well as microwave energy, to develop a rapid processing method. The effect of this method on the quality of histomorphology, histochemistry, immunohistochemistry, and RNA content of processed tissue was compared with that of adjacent tissue sections processed by the conventional processing technique. We also assessed the impact of this rapid processing system on our practice by comparing the turnaround times of surgical pathology reports before and after its implementation. RESULTS: The new processing method permitted preparation of paraffin blocks from fresh or prefixed tissue in about 1 hour. The procedure allowed continuous flow of specimens at 15-minute intervals. It eliminated the use of formalin and xylene in the processing and used considerably lower volumes of other chemical reagents. Histomorphologic, histochemical, and immunohistochemical results were comparable to the parallel sections prepared by the conventional method. The new technique, however, preserved higher quality RNA. Use of the new methodology led to the diagnosis and reporting of more than one third of surgical pathology specimens on the same day that they were received, as compared to 1% of same-day reporting before the implementation of the rapid processing system. CONCLUSION: The quality of hematoxylin-eosin, histochemical, and immunohistochemical tissue sections provided by the new system is comparable to that obtained following the conventional processing method. The new system preserves RNA better than the conventional method. It also shortens the processing time to about 1 hour from the receipt of fresh or prefixed tissue, eliminates the need for formalin and xylene, and reduces the volume of other chemicals. Most importantly, it impacts overall patient management by allowing for considerably shorter turnaround times for completion of surgical pathology reports.

Female↗
PubMedDate not supplied

Mutations in the p53 tumor suppressor gene and early onset breast cancer.

Among breast cancer patients p53 gene mutation is associated with a poor prognosis. Young women with breast cancer are more likely than older women to have a poor prognosis, but whether p53 gene mutation plays a role in breast cancer in young women is not clear. This study identified 199 breast cancer patients and tested the hypothesis that p53 gene mutation was associated with early onset breast cancer. Patients with p53 gene mutations were 3-times more likely to have an early onset breast cancer (age < or = 40 years at diagnosis) than those without p53 mutations (OR = 3.05, 95% CI = 1.10-8.45). Patients with both missense and silent mutations were 7-times more likely to have a diagnosis of early onset breast cancer (OR = 7.56, 95% CI = 2.22-25.8). Patients with mutations in exon 8 of the p53 gene were 6-times more likely to be diagnosed with early onset breast cancer (OR = 6.48, 95% CI = 1.37-30.6). These findings suggest that p53 gene mutation may hasten the onset of female breast cancer.

Adult↗