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Immunohistochemical Markers (immunohistochemical + marker)
Kinds of Immunohistochemical Markers Selected AbstractsAssessment of Proliferating Cell Nuclear Antigen Activity Using Digital Image Analysis in Breast Carcinoma Following Magnetic Resonance-Guided Interstitial Laser PhotocoagulationTHE BREAST JOURNAL, Issue 5 2003Soheila Korourian MD Abstract: This study examines proliferative activity in tumor cells of patients with histologically documented invasive breast carcinoma treated with magnetic resonance-guided interstitial laser photocoagulation (MR-GILP). Immunohistochemical marker for proliferating cell nuclear antigen (PCNA), a nuclear protein abundant in actively proliferating cells, is used. The study demonstrates the effectiveness of MR-GILP in ablating tumor cells of infiltrating breast cancer. The diagnosis of infiltrating breast carcinoma was confirmed by core needle biopsies. Using a specially designed magnetic resonance imaging (MRI) device, rotating delivery of excitation off-resonance (RODEO), tumors were measured ranging from 1.8 to 4.0 cm in greatest dimension. Seven formalin-fixed, paraffin-embedded archival tissues from seven patients with infiltrating carcinoma, status post-MR-GILP, were analyzed. Using PCNA immunoperoxidase (Biomeda Corp.), the proliferative capability of the remaining tumor cells around the focus of laser photocoagulation was determined. The lesions were digitally acquired using a Nikon Eclipse E800 microscope with an automated stage. Images were analyzed using Cool SNAP image editing software (version 1.0). Appropriate thresholds were set for positive staining and limited concentric radial measurements of equal area between all samples were compared at radial millimeter intervals from the center of laser ablation. The integrated area occupied by PCNA-positive cells per radial millimeter from the charcoal site (the center of the laser) increased as the distance from this site increased (a mean average at each radial measurement revealed: at the 1 mm radius the positive integrated area was 0.0024 mm2; at 2 mm, 0.0145 mm2; at 3 mm, 0.0351 mm2; at 4 mm, 0.0696 mm2; at 5 mm, 0.1025 mm2; and at 6 mm, 0.1263 mm2). MR-GILP is an effective mean of ablating breast carcinoma. This treatment option may represent an alternative to lumpectomy for a single lesion ,1 cm, or make patients with two separate lesions eligible for lumpectomy. [source] Secondary prostatic adenocarcinoma: A cytopathological study of 50 casesDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2007F.R.C.P.C., Kien T. Mai M.D. Abstract Positive diagnosis of metastatic prostate adenocarcinoma (PAC) can be made by microscopic examination of the cytologic specimens and immunostaining for prostate-specific antigen (PSA) and prostate acid phosphatase (PAP). Immunohistochemical markers have been known to display negative, weak, or focal staining in poorly differentiated PAC and in patients with prior hormonal and/or radiation therapy. The purpose of this study is to characterize the cytopathology of metastatic PAC as it has not been documented in large series. Fifty cases of metastatic PAC with cytological specimens consisting of 41 fine-needle aspiration biopsies (FNAB), 6 pleural fluid aspirates, and 3 catheterized urine samples were reviewed and correlated with the surgical specimens and the clinical charts. Immunostaining for PSA, PAP, cytokeratin AE1/3, cytokeratin 7 (CK7), cytokeratin 20 (CK20), vimentin, and carcinoembryonic antigen (CEA) was done. Mean patient age was 77 ± 8 yr; serum PSA, 4.1 ± 2.3; and primary PAC Gleason score, 8.1 ± 1.5. Cytologically, the specimens consisted of cell clusters or cell sheets with overlapping uniform hyperchromatic nuclei with or without nucleoli. Twelve cases were not reactive to PSA and PAP and 44 cases displayed negative immunoreactivity to both CK7 and CK20. Carcinoid-like lesions and small cell carcinomas were seen in 4 cases and were misdiagnosed as nonprostatic origin based on the following features: negative immunoreactivity to PSA and PAP with or without positive reactivity to CEA, and different histopathological features when compared with the primary PAC. In addition to the frequency of high-grade PAC, awareness of the negative immunoreactivity to PSA and PAP, the discrepancy in the histopathological patterns between the primary and secondary tumors, especially the frequent neuroendocrine differentiation, are helpful features for the diagnosis of metastases of prostatic origin. Diagn. Cytopathol. 2007;35:91,95. © 2007 Wiley-Liss, Inc. [source] Caveolin-1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinomaHISTOPATHOLOGY, Issue 1 2009Vishwa Jeet Amatya Aims:, The incidence of mesothelioma is increasing in Europe, Japan and other developing countries. There is difficulty in the accurate diagnosis of mesothelioma and its differentiation from lung adenocarcinoma. Mesothelioma shows a complex immunohistochemical profile. Therefore, the use of a immunohistochemical panel that includes both positive and negative mesothelial markers has become a general rule for its accurate diagnosis. However, they are still not sufficient. The aim was to assess the diagnostic utility of caveolin-1 (Cav-1), which is expressed in endothelial cells, alveolar type I pneumocytes and mesothelial cells, as a novel positive marker of mesothelioma. Methods and results:, An immunohistochemical study of 80 cases of epithelioid mesothelioma and 80 cases of lung adenocarcinoma was performed for the analysis of the expression of Cav-1 and other markers. Cav-1 expression with a membranous and/or cytoplasmic pattern was found in all of the epithelioid mesothelioma. Of these, 42 cases (52.5%) showed Cav-1 expression in >50% of tumour cells, 34 cases (42.5%) in 6,50% of tumour cells, and four cases (5.0%) in <5% of tumour cells. In contrast, only six cases (7.5%) of lung adenocarcinoma showed focal Cav-1 expression in the cytoplasm of the tumour cells. The sensitivity and specificity of Cav-1 expression for the differentiation of epithelioid mesothelioma from lung adenocarcinoma were 100 and 92.5%, respectively. This is comparable or even superior to that of currently available positive markers such as calretinin or D2-40. Conclusions:, Cav-1 is a novel immunohistochemical marker for the differentiation of epithelioid mesothelioma from lung adenocarcinoma. [source] Mutant L Homologue 1 (MLH1): a possible new immunohistochemical marker for prostatic cancerHISTOPATHOLOGY, Issue 2 2008S-T Chuang No abstract is available for this article. [source] Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord,stromal tumoursHISTOPATHOLOGY, Issue 5 2001W G McCluggage Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord,stromal tumours Aims:,Ovarian sex cord,stromal tumours are a heterogeneous group of neoplasms which may be confused morphologically with a wide variety of tumours. Calretinin positivity has previously been demonstrated in a small number of ovarian sex cord,stromal tumours. The aim of this study was to investigate calretinin staining in a series of these tumours and their histological mimics in order to determine the value of calretinin staining in a diagnostic setting. Methods and results:,Seventy-two neoplasms, including 37 ovarian sex cord,stromal tumours and 35 miscellaneous neoplasms which may enter into the differential diagnosis, were stained with a commercially available polyclonal antibody against calretinin. All sex cord,stromal tumours exhibited positivity except for a single fibrothecoma. In this group of tumours staining was generally diffuse and strong. Small numbers of the miscellaneous group of neoplasms exhibited positivity but this tended to be focal and weak, although this was not always the case. There was consistent strong positive staining of granulosa cells in follicular cysts and corpora lutea. There was also positive staining of luteinized stromal cells in two cases of ovarian stromal hyperplasia and hyperthecosis. Conclusions:,Calretinin is a sensitive immunohistochemical marker of ovarian sex cord,stromal tumours and may be useful in a diagnostic setting. However, the value is somewhat limited since occasional neoplasms which enter into the morphological differential diagnosis may be positive. Be that as it may, calretinin positivity may be of value in the diagnosis of an ovarian sex cord,stromal tumour and its differentiation from other neoplasms. In this regard, calretinin should always be used as part of a larger panel. [source] Expression of PGP 9.5 in granular cell nerve sheath tumors: an immunohistochemical study of six casesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2001Meera Mahalingam Background: Protein gene product 9.5 (PGP 9.5) is expressed in brain at 20 to 50 times the levels detected in other organs. Immunohistochemical studies reveal this protein is localized to both central and peripheral neurons. Recently, PGP 9.5 is reported to be a useful marker for cellular neurothekeomas. Herein we test whether PGP 9.5 is a new marker for granular cell nerve sheath tumors. Material and Methods: An immunohistochemical analysis for PGP 9.5 expression was carried out on all cases with the diagnosis of granular cell nerve sheath tumor seen over a 2-year period. In addition, we compared expression of PGP 9.5 with other accepted markers for neuroectodermal tumors including anti-S-100 protein and NKI/C3 monoclonal antibodies. Results: Six granular cell nerve sheath tumors were diagnosed in over 80,000 dermatopathology specimens in the two-year period. These cases were all positive for PGP 9.5 as well as for S-100 protein and NK1/C3. Conclusion: These findings identify PGP 9.5 as a new immunohistochemical marker for use in the diagnosis of granular cell tumors. They also strengthen the histogenetic relationship between granular cell nerve sheath tumors and tumors of Schwann cell or perineurial origin. [source] Hypoxia-inducible factor 1, may be a marker for vasculitic neuropathyNEUROPATHOLOGY, Issue 6 2007Nobuyuki Oka Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia-inducible factor 1, (HIF-1,) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty-one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF-1, and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF-1,-positive nuclei was significant. Two patients with possible vasculitis who showed HIF-1,-positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF-1,-IR. HIF-1, may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions. [source] PKC theta, a novel immunohistochemical marker for gastrointestinal stromal tumors (GIST), especially useful for identifying KIT-negative tumorsPATHOLOGY INTERNATIONAL, Issue 3 2005Atsushi Motegi Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the digestive tract and the majority of GIST has characteristic gain-of-function mutations of the c-kit gene, which encodes the KIT receptor for stem cell factor. The present study aimed to establish the usefulness of protein kinase C theta (PKC ,) as an immunohistochemical marker for GIST in comparison with KIT immunohistochemistry. PKC , immunohistochemistry was carried out not only on 48 cases of GIST and another 40 cases of gastrointestinal mesenchymal tumors, but also on 24 cases of various tumors known to be immunohistochemically positive for KIT. Immunohistochemically, 41 out of 48 cases (85%) of GIST were positive for PKC ,, and its expression was confirmed by Western blot analysis using six cases of surgically resected GIST. In the present study there were six GIST immunohistochemically negative for KIT, which histologically revealed a myxoid epithelioid appearance characteristic to that of GIST with platelet-derived growth factor receptor alpha mutation. All six GIST were immunohistochemically positive for PKC ,. No PKC , immunoreactivity was observed in other gastrointestinal mesenchymal tumors and various KIT-positive tumors except for three cases (14%) of gastrointestinal schwannomas. The present study revealed that PKC , is an immunohistochemically novel and useful marker for GIST, especially for GIST negative for KIT. [source] Proliferative and apoptotic differences between alveolar rhabdomyosarcoma subtypes: A comparative study of tumors containing PAX3-FKHR or PAX7-FKHR gene fusionsPEDIATRIC BLOOD & CANCER, Issue 2 2001Margaret H. Collins MD Abstract Background Most alveolar rhabdomyosarcomas (ARMS) have chromosome translocations and resultant gene fusion products. The more common translocation fuses the PAX3 and FKHR genes; patients who have PAX3-FKHR-positive ARMS have reduced event-free survival compared to patients with ARMS containing the less common translocation that fuses the PAX7 and FKHR genes. Procedure We examined histology, immunohistochemical markers of differentiation, and cell cycle characteristics of a panel of ARMS containing either PAX3-FKHR or PAX7-FKHR transcript to determine if these features differ between the ARMS subsets. Results Cell cycle parameters varied significantly: the number of nuclei that stained with either an immunohistochemical marker of proliferation (MIB1), or a TUNEL-based assay for apoptosis was significantly greater in tumors that expressed PAX3-FKHR compared to tumors that expressed PAX7-FKHR transcript. Conclusions We conclude that compared to PAX7-FKHR-containing tumors, ARMS that contain PAX3-FKHR transcript have (1) increased cell proliferation, consistent with greater loss of cell cycle regulation, and (2) apoptosis that is increased but insufficient to prevent tumor formation. More marked cell cycle dysregulation may contribute to poorer prognosis for patients with ARMS that have PAX3-FKHR fusion. Med Pediatr Oncol 2001;37:83,89. © 2001 Wiley-Liss, Inc. [source] Sentinel lymph nodes in malignant melanomaCANCER, Issue 8 2004Extended histopathologic evaluation improves diagnostic precision Abstract BACKGROUND The optimal technique for sentinel lymph node (SN) assessment in patients with melanoma is controversial. Molecular analysis (reverse transcriptase,polymerase chain reaction) detects significantly greater numbers of SNs with suspected micrometastases (up to 71%) than does routine histopathology (approximately 20%). The authors sought to identify possible reasons for this discrepancy and to determine whether using an extended histopathologic protocol could improve diagnostic precision. METHODS Two hundred thirty-one SNs from 100 consecutive patients with cutaneous melanomas that measured 1,4 mm in thickness were bisected, and half of the lymph node was examined according to an extensive histopathologic protocol involving serial sectioning and immunohistochemical analysis of 3 melanocyte-associated markers (S-100, HMB-45, and Melan-A). RESULTS Lymph node melanocytic lesions were frequent, with micrometastases and benign nevus inclusions (BNI) found in SNs in 28% and 28% of patients, respectively (4 SNs contained both). Melan-A was the most sensitive immunohistochemical marker and was positive in all BNI-positive SNs and 97% of micrometastasis-positive SNs. Although HMB-45 showed differential labeling in micrometastases compared with BNI (82% vs. 16%), immunohistochemistry could not distinguish between those lesions. Micrometastases were already identified on the first central level in 49% of positive SNs, whereas only 23% of SNs with BNI were diagnosed on the first level. CONCLUSIONS Extensive serial sectioning with immunohistochemical analysis substantially increased the histopathologic detection of micrometastases and BNI in melanoma SNs to a level approaching the level reported for molecular techniques. The large number of BNIs represents an important potential source of imprecision (false positivity) in SN assays based on nonmorphologic methods. Cancer 2004. © 2004 American Cancer Society. [source] Aspiration biopsy cytology of extraabdominal desmoid tumor concurrently occurring in a patient with tumoral calcinosisDIAGNOSTIC CYTOPATHOLOGY, Issue 9 2008F.I.A.C., Husain Saleh M.D., M.B.A. Abstract Extraabdominal fibromatosis or desmoid tumor (DT) is a slow growing locally aggressive soft tissue tumor that can occur anywhere in the body. We report the aspiration biopsy cytology features of a case of DT of the right neck area in a 35-year-old man who had a long standing history of tumoral calcinosis. The aspirate was interpreted as "benign spindle cell lesion" and confirmed as DT on histologic examination of the resected mass. We discuss the possible differential diagnoses of other benign or malignant lesions on fine-needle aspiration (FNA) biopsy and especially discuss the aspiration cytology features of DT compared with those of tumoral calcinosis. We also discuss the value of immunohistochemical markers that help in differentiating DT from other entities. Diagn. Cytopathol. 2008;36:624,627. © 2008 Wiley-Liss, Inc. [source] The effects of antibody clone and pretreatment method on the results of HER2 immunostaining in cytologic samples of metastatic breast cancer: A query and a review of the literature,,§DIAGNOSTIC CYTOPATHOLOGY, Issue 6 2007Patricia A. Fetsch M.T. (ASCP) Abstract The standardization and use of heat-induced epitope retrieval (HIER) is particularly important with immunohistochemical markers that direct the course of cancer treatment, such as Herceptin therapy. Increasingly, many laboratories are performing immunohistochemical analysis using various antibodies and methodologies for HER2/neu. We attempted to determine the effects of antibody clone and pretreatment methods on the interpretation of HER-2/neu staining in cytologic samples. Cell block sections from 54 cases of metastatic breast cancer (24 FNAs, 30 effusions) were analyzed for HER2 expression using antibodies to CB-11, TAB250, and A0485. Antibodies were analyzed with and without HIER. One pathologist using the FDA-approved scoring system for the HercepTest reviewed all slides in a blinded fashion. Five of fifty-four cases (9%) using CB-11 showed a significant increase in HER2 immunoreactivity using HIER (i.e. from 0/1+ to 2,3+). However, in twenty-nine of fifty-four cases (54%), the cytoplasmic background was significantly higher after HIER. With the A0485 antibody, two of fifty four cases (4%) showed a significant increase in immunoreactivity using HIER, while seventeen of fifty-four cases (31%) exhibited only more pronounced cytoplasmic staining. HIER pretreatment did not increase HER2 staining in any TAB250 stained sample, rather four of fifty-four cases (7%) showed a significant decrease in staining with HIER. We conclude that HIER may enhance membrane staining with the CB-11 and A0485 antibodies, but also increases cytoplasmic background. Loss of antigenicity is seen when HIER is used with TAB250. Diagn. Cytopathol. 2007;35:319,328. © 2007 Wiley-Liss, Inc. [source] Myopericytoma of the oral cavityHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2007Vivekanand Datta MD Abstract Background. Myopericytoma is a rare mesenchymal neoplasm of pericytic cells demonstrating myoid differentiation. The lesion typically arises within the subcutaneous tissue of the extremities. We report a case that, to the best of our knowledge, is the first case of myopericytoma involving the soft tissue of the oral cavity. Methods. A 36-year-old woman had a 5-mm sessile, whitish-pink, firm tongue nodule. The patient underwent excisional biopsy, and histopathologic examination as well as immunohistochemical analysis were performed. Results. The differential diagnosis by histologic analysis included solitary fibrous tumor, myofibroma, glomus tumor, and myopericytoma. The results of immunohistochemical analysis, when combined with the histologic features, led to a diagnosis of myopericytoma. Conclusions. Applying strict morphologic criteria and appropriately selective immunohistochemical markers will help to distinguish myopericytoma in the oral cavity. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] ERG rearrangement in small cell prostatic and lung cancerHISTOPATHOLOGY, Issue 7 2010Veit J Scheble Scheble V J, Braun M, Wilbertz T, Stiedl A-C, Petersen K, Schilling D, Reischl M, Seitz G, Fend F, Kristiansen G & Perner S (2010) Histopathology,56, 937,943 ERG rearrangement in small cell prostatic and lung cancer Aims:, Small cell prostatic cancer is a rare but aggressive disease. Currently, its histogenetic origin is unclear and its distinction from metastatic small cell lung cancer is challenging. The aim of our study was to determine whether the ERG rearrangement commonly observed in acinar prostatic cancer can distinguish small cell prostatic cancer from small cell lung cancer samples. Methods and results:, We assessed 15 small cell prostatic cancers and 22 small cell lung cancers for ERG rearrangement using fluorescence in situ hybridization. Commonly used and novel immunohistochemical markers (i.e. androgen receptor, calcium activated nucleotidase 1, Golgi phosphoprotein 2, prostate-specific antigen, prostate-specific membrane antigen, CD56, epithelial membrane antigen, thyroid transcription factor 1, chromogranin A, synaptophysin and Ki67) were further studied. ERG rearrangement occured in 86% of small cell prostatic cancers but in none of the small cell lung cancers and was the best marker to differentiate between both tumours (P < 0.0001). Conclusions:, The ERG rearrangement is commonly observed in small cell prostatic cancer, supporting the hypothesis that ERG rearrangement occurs in aggressive prostatic cancers. Furthermore, the ERG rearrangement is the most significant marker to differentiate between small cell prostatic cancer and small cell lung cancer. Moreover, our data suggest that small cell prostatic cancer is not a tumour entity on its own, but a dedifferentiated variant of common acinar prostatic cancer. [source] Histogenesis of Abrikossoff tumour of the oral cavityINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 1 2010F Haikal Abstract:, Background:, Abrikossoff or granular cell tumour (GCT) is a relatively rare neoplasia, benign in most of the cases. It may occur in any part of the human body, but it has an oral location in 70% of the cases. Its origin has been discussed for decades, and it is not yet definitively determined. Immunohistochemical techniques suggest its origin in the Schwann cells, while more recent studies with new markers indicate an origin related to neuroendocrine cells. Objective:, Contribute to the clarification of histogenesis of oral Abrikossoff tumour studying immunohistochemical marking of 11 oral Brazilian cases. Materials and methods:, Samples of tissues from the oral mucosa, tongue and lips placed in paraffin blocks, from eleven patients with a histopathological diagnosis of benign GCT were studied. Four different anti-serums (S-100, vimentin, PGP9.5 and ENE) were used for immunoperoxydase technique. Results:, A clear positivity for S-100 protein and vimentin was observed, with markers indicating origin from the Schwann cells. Less intense positivity was found in some cases, for ENE and PGP9.5, which suggests a neuroendocrine origin. Conclusions:, The results obtained suggest an origin from Schwann cells, but also arise the possibility of neuroendocrine origin. New methods and more specific immunohistochemical markers are needed to elucidate the origin of the Abrikossoff tumour. [source] Liver sinusoidal endothelial cells and acute non-oxidative hepatic injury induced by Pseudomonas aeruginosa pyocyaninINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2008Rajkumar Cheluvappa Summary The liver sinusoidal endothelial cell (LSEC) is damaged by many toxins, including oxidants and bacterial toxins. Any effect on LSECs of the Pseudomonas aeruginosa virulence factor, pyocyanin, may be relevant for systemic pseudomonal infections and liver transplantation. In this study, the effects of pyocyanin on in vivo rat livers and isolated LSECs were assessed using electron microscopy, immunohistochemistry and biochemistry. In particular, the effect on fenestrations, a crucial morphological aspect of LSECs was assessed. Pyocyanin treatment induced a dose-dependent reduction in fenestrations in isolated LSECs. In the intact liver, intraportal injection of pyocyanin (11.9 ,M in blood) was associated with a reduction in endothelial porosity from 3.4 ± 0.2% (n = 5) to 1.3 ± 0.1% (n = 7) within 30 min. There were decreases in both diameter and frequency of fenestrations in the intact endothelium. There was also a decrease in endothelial thickness from 175.8 ± 5.8 to 156.5 ± 4.0 nm, an endothelial pathology finding previously unreported. Hepatocyte ultrastructure, liver function tests and immunohistochemical markers of oxidative stress (3-nitrotyrosine and malondialdehyde) were not affected. Pyocyanin induces significant ultrastructural changes in the LSEC in the absence of immunohistochemical evidence of oxidative stress or hepatocyte injury pointing to a novel mechanism for pyocyanin pathogenesis. [source] Cell proliferation and differentiation during fracture healing are influenced by locally applied IGF-I and TGF-,1: Comparison of two proliferation markers, PCNA and BrdUJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2003B. Wildemann Abstract Growth factors IGF-I and TGF-,1 are known to stimulate fracture healing. The purpose of this study was to investigate the role of locally applied IGF-I and TGF-,1 during the early phase of fracture healing (Days 5, 10, and 15 after fracture) on cellular processes like proliferation and differentiation in a rat model. Two different immunohistochemical markers were used to analyze cell proliferation: (1) injection of the thymidine analogue BrdU and subsequent immunohistochemical staining for BrdU-positive nuclei, and (2) the antibody against the "proliferating cell nuclear antigen" (PCNA). In comparison, both methods revealed similar results concerning the types of proliferating cells at the different time points and the two groups. Labeling indices of both methods showed very good correlation (e.g., rs: 0.887 and p < 0.001 at day 10 in the control group without growth factors). Comparison of the callus morphology and the proliferation rate showed differences during fracture healing due to the local application of IGF-I and TGF-,1 from coated implants. At Day 5 the callus of the group treated with growth factors displayed an earlier appearance of cartilage compared to the control group. This was accompanied by an onset of cell proliferation in chondrocytes. Likewise, at the later time points an enhanced maturation of the callus tissue and the proliferation pattern were detectable in the growth-factor group. These results indicate that local application of IGF-I and TGF-,1 accelerates early cellular processes during fracture healing. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 65B: 150,156, 2003 [source] Morphological and immunohistochemical characteristics of atypical fibroxanthoma with a special emphasis on potential diagnostic pitfalls: a reviewJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2010tjan Luzar The present manuscript gives emphasis on recognizing different morphological variants of atypical fibroxanthoma (AFX), on validation of immunohistochemical markers and on discussing potential diagnostic pitfalls. Material and methods: Histological features analyzed in 66 AFXs were: ulceration, morphological variants, growth pattern, location in the skin and vascular/perineural invasion. The antibodies used were CK-MNF116, CK-AE1/AE3, S100, smooth muscle actin, desmin, CD31 and EMA. Results: The study included 59 males, 7 females, aged 55,95 years, mean 77 years. All developed on sun damaged skin. Ulceration was present in 50%. Morphological patterns were pleomorphic spindle and epithelioid cells (60.6%), predominantly spindle cells (19.7%), purely spindle-cells (13.6%), and predominantly epithelioid cells (6.1%). Most were localized in the dermis (57.6%). An expansile (36.4%) rather than infiltrative (6.1%) growth into superficial subcutis was also noted. No vascular/perineural invasion was seen. Additional changes were hemorrhagic and pseudoangiomatous areas (24.2%), granular cell change (22.7%), keloid-like areas (9.1%), myxoid change (7.6%), osteoclast-like giant cells (6.1%) and clear cell change (4.6%). AFXs were consistently negative for S100, CK-MNF116, CK-AE1/AE3 and desmin. Focal positivity for SMA (45.2%), EMA (24.4%) and CD 31 (9.5%) was seen. Conclusions: A diagnosis of AFX is still made by exclusion of other malignant neoplasms with similar morphology. Immunohistochemistry plays a crucial role in this distinction, but can also be misleading. This study expands the spectrum of non-vascular CD31 positive tumors. Luzar B, Calonje E. Morphological and immunohistochemical characteristics of atypical fibroxanthoma with a special emphasis on potential diagnostic pitfalls. [source] Immunohistochemical characteristics of melanomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2008Steven J. Ohsie Melanoma has a wide spectrum of histologic features which mimic epithelial, hematologic, mesenchymal, and neural tumors. Immunohistochemistry has been the primary tool to distinguish melanomas from these other tumors; it has also been studied for use as an adjunct to distinguish benign and malignant melanocytic tumors and to elucidate prognosis. Furthermore, there has been extensive effort to find a suitable marker to differentiate spindle cell and desmoplastic melanoma from other tumors. We have reviewed the literature investigating melanocytic differentiation markers, proliferation markers, immunomodulatory markers, signaling molecules, and nerve growth factors and receptors. Despite the proliferation of immunohistochemical markers, S-100 remains the most sensitive marker for melanocytic lesions, while markers such as HMB-45, MART-1/Melan-A, tyrosinase, and MITF demonstrate relatively good specificity but not as good sensitivity as S-100. No marker has proven useful in distinguishing spindle cell and desmoplastic melanomas from other tumors. Ki67 remains the most useful adjunct in distinguishing benign from malignant melanocytic tumors. None of the markers reviewed has been shown conclusively to have prognostic value for melanocytic neoplasms. [source] Mast cell tryptase and microphthalmia transcription factor effectively discriminate cutaneous mast cell disease from myeloid leukemia cutisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2007Uma N. Sundram Background:, Cutaneous mast cell disorders are uncommon, but a subset, especially mastocytoma and mast cell leukemia, can histologically mimic myeloid leukemia cutis. Our objective was to employ a panel of cytochemical and immunohistochemical markers to determine which ones would be most useful in separating these two entities. Methods:, We stained 17 cases of cutaneous mast cell disease and 20 cases of myeloid leukemia cutis with Giemsa, toluidine blue, or pinacyanol erythrosinate (PE), as well as with antibodies against mast cell tryptase, microphthalmia transcription factor (MiTF), CD117 (c-kit), myeloperoxidase, CD43, CD25, CD2, and CD68. Results:, Mast cell tryptase and MiTF emerged as highly sensitive and specific markers for mast cell disease in this context, as both antibodies stained all cases of mast cell diseases but none of myeloid leukemia cutis. Although CD117 stained all cases of mast cell disease, it also stained 2 of 18 cases of myeloid leukemia cutis. PE appeared to be specific for mast cell disease, as 11 of 12 cases stained with this marker, compared with 0 of 18 cases of myeloid leukemia cutis. Conclusions:, Our results show that mast cell tryptase and MiTF are equally effective in distinguishing mast cell disease from myeloid leukemia cutis. [source] Immunohistochemical Expression of Cutaneous LeiomyosarcomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005P. Bhattacharjee Immunohistochemistry plays a vital role in distinguishing cutaneous leiomyosarcoma (CLMS) from other spindle cell neoplasms. Recently, several new immunohistochemical markers of smooth muscle differentiation (calponin, h-caldesmon) have shown greater utility in the diagnosis of CLMS. We compared the expression of various traditional and novel immunohistochemical markers in CLMS. Thirteen cases of CLMS were immunostained with a panel of antibodies (SMA, MSA, desmin, vimentin, S100, cytokeratin, NSE, HMB-45, CD117, procollagen, h-caldesmon and calponin. Immunostaining was graded from 0 to 4+ based on the percentage of positive staining. All 13 cases of CLMS showed positive staining with SMA, MSA and h-caldesmon. 12 cases showed positive staining with desmin, calponin, vimentin and NSE. 8 cases showed positive staining with CD117 and procollagen. 4 and 3 cases showed focal positive staining for S100 and cytokeratin. All cases were HMB-45 negative. All 13 cases exhibited greater than 50% staining with SMA and MSA. 11 cases were strongly positive (>50%) for calponin and h-caldesmon, while only 8 cases were strongly positive for desmin. Our study finds no significant difference between traditional and novel smooth muscle immunostains. We conclude that a panel of immunohistochemical stains should be employed to differentiate CLMS from other spindle cell neoplasms. [source] Changes in immune and enzyme histochemical phenotypes of cells in the intestinal mucosa of Atlantic salmon, Salmo salar L., with soybean meal-induced enteritisJOURNAL OF FISH DISEASES, Issue 2 2000A M Bakke-McKellep Extracted soybean meal (SBM) in the diet for Atlantic salmon, Salmo salar L., causes an inflammatory response in the distal intestine. The morphological changes of the epithelial cells and a characterization of the inflammatory cell infiltrate of the distal intestinal mucosa were studied using a panel of enzyme and immunohistochemical markers. The salmon (average body weight 927 g) used in the study were fed either a fishmeal-based diet (control diet) or a diet in which 30% of the fishmeal protein was replaced with SBM protein (SBM diet). In salmon fed SBM, there were markedly reduced enzyme reactivities in the distal intestinal epithelial cells, both in the brush border [5,-nucleotidase (5,N), Mg2+-ATPase, alkaline phosphatase (ALP) and leucine aminopeptidase (LAP)] and in the intracellular structures [alkaline and acid phosphatase, non-specific esterase (NSE) and alanine aminopeptidase (AAP)]. There appeared to be an increased presence of cells of monocytic lineage, including macrophages, as well as neutrophilic granulocytes and immunoglobulin (Ig) M in the lamina propria of the SBM-fed fish. The mid intestine showed little response to the diet. The results suggest that toxic/antigenic component(s) of SBM affect the differentiation of the distal intestinal epithelial cells and may help explain the reduced nutrient digestibilities previously reported in salmonids fed extracted SBM. [source] Renaut bodies in nerves of the trunk of the African elephant, Loxodonta africanaJOURNAL OF MORPHOLOGY, Issue 5 2007Kirsti Witter Abstract Renaut bodies are loosely textured, cell-sparse structures in the subperineurial space of peripheral nerves, frequently found at sites of nerve entrapment. The trunk of the elephant is a mobile, richly innervated organ, which serves for food gathering, object grasping and as a tactile organ. These functions of the trunk lead to distortion and mechanical compression of its nerves, which can therefore be expected to contain numerous Renaut bodies. Samples of the trunk wall of an adult African elephant (Loxodonta africana) were examined histologically using conventional staining methods, immunohistochemistry, and lectin histochemistry. Architecture of nerve plexuses and occurrence of Renaut bodies in the elephant trunk were compared with those in tissues surrounding the nasal vestibule of the pig. Prominent nerve plexuses were found in all layers of the elephant trunk. Almost all (81%) nerve profiles contained Renaut bodies, a basophilic, discrete subperineurial layer resembling cushions around the nerve core. In contrast, Renaut bodies were seen in only 15% of nerve profiles in the porcine nasal vestibule. Within Renaut bodies, fusiform fibroblasts and round, ruff-like cells were placed into a matrix of acidic glycosaminoglycans with delicate collagen and very few reticular fibers. The turgor of this matrix is thought to protect nerves against compression and shearing strain. Renaut bodies are readily stained with alcian blue (pH 2.5) favorably in combination with immunohistochemical markers of nerve fibers. They should be regarded as a physiological response to repeated mechanical insults and are distinct from pathological alterations. alterations. J. Morphol., 2007. © 2007 Wiley-Liss, Inc. [source] Hepatocyte senescence in end-stage chronic liver disease: a study of cyclin-dependent kinase inhibitor p21 in liver biopsies as a marker for progression to hepatocellular carcinomaLIVER INTERNATIONAL, Issue 5 2007Elizabeth M. Brunt Abstract Background: Histologic markers to predict hepatocellular carcinoma (HCC) include small cell change and dysplastic nodules. Hepatocyte senescence is noted in chronic liver disease and may or may not be important in progression to HCC. Aim: The study was undertaken to compare standard histologic features of chronic liver disease as well as markers of senescence and proliferation in two groups of biopsies from patients followed for at least a year. Methods: Standard histologic evaluation of necroinflammatory activity, fibrosis, steatosis, and iron, internationally accepted criteria of dysplasia, and immunohistochemical markers for proliferation and hepatocyte senescence were compared in 47 liver biopsies from noncholestatic chronic liver disease patients who subsequently either underwent transplant (the Control group, n=19) or had biopsy-proven (HCC group, n=28) over a similar time period of 34.9 months (mean) and 42.5 months (mean) respectively. Results: Both groups were predominantly men; the MELD score was higher, and mean age was less in the Control group (46.9 vs 53.8 years, P=0.01). Small cell change was not significantly different in the biopsies between the two groups; neither were grade, stage (Ishak scores), nor presence or location of iron. Steatosis was more common in the group that subsequently developed HCC (P=0.04). The MIB-1 proliferation index was greater in the biopsies from the Control group. The senescence marker p21, and the ratio of p21:MIB-1 were not statistically different between the two groups. However, a Spearman's rank correlation showed a linear correlation of p21/MIB-1 with a greater amount of dyplasia in the explant livers of Controls. Conclusions: These findings suggested the Control groups' livers maintained effective removal of cells from the cell cycle by overexpression of p21 and, while not ,protected' from significant involvement by dysplasia, may have been precluded from development of HCC. [source] TrkA expression is associated with an elevated level of apoptosis in classic medulloblastomasNEUROPATHOLOGY, Issue 3 2006Takashi Ohta Medulloblastomas represent the most common central nervous system malignancies in children. Despite intensive modality treatment with craniospinal irradiation and multiple drug chemotherapy, their prognosis remains dismal. In the present study, we examined the potential roles of cellular differentiation, proliferation and apoptosis in 21 pediatric patients with newly diagnosed classic medulloblastomas treated by conventional radiation therapy and adjuvant chemotherapy. The expression of glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC, and the proliferation index of MIB-1 were evaluated by immunohistochemistry and the apoptotic index was determined using terminal deoxytransferase-mediated deoxyuridine-5,-triphosphate nick-end labeling assay. The prognostic value of these biological markers was also assessed. Immunoreactive glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC were observed in seven (33%), four (19%), 12 (57%), 14 (67%) and 11 (52%) of the 21 cases, respectively. TrkA expression was positively correlated with the MIB-1 staining index (P = 0.0228) and the apoptotic index (P = 0.0058). None of the immunohistochemical markers was found to be of value in predicting the prognosis. Although the present small sample size does not provide sufficient power to discount biological variables as prognostic markers, it was the well-established clinical prognostic factors, i.e. tumor stage and extent of surgery, that stood out as the most important predictors of survival. The close association between apoptosis and TrkA expression is consistent with in vitro data demonstrating the capacity of the NGF/TrkA signaling pathway to increase medulloblastoma apoptotic cell death, suggesting that this pathway may yield alternative therapeutic targets for novel therapies. [source] Nestin expression as a new marker in malignant peripheral nerve sheath tumorsPATHOLOGY INTERNATIONAL, Issue 2 2007Satoko Shimada Malignant peripheral nerve sheath tumor (MPNST) can be difficult to diagnose because it lacks specific immunohistochemical markers. S-100, which is a useful marker of MPNST, has limited diagnostic utility. Recent studies suggest that nestin, which is an intermediate filament protein, is expressed in neuroectodermal stem cells. The diagnostic utility of immunostains for nestin and three other neural markers (S-100, CD56 and protein gene product 9.5 (PGP 9.5)) were evaluated in 35 cases of MPNST and in other spindle cell tumors. All MPNST cases were strongly positive for nestin and had cytoplasmic staining. Stains for S-100, CD56, and PGP 9.5 were positive in fewer cases (17/35, 11/35, and 29/35 cases, respectively), and had less extensive staining. Nestin was negative in 10/10 leiomyomas, and weak nestin expression was seen in 10/10 schwannomas, 3/10 neurofibromas, 2/8 synovial sarcomas, 2/10 liposarcomas, 4/7 carcinosarcomas and 3/7 malignant fibrous histiocytomas. In contrast, strong nestin positivity was seen in 10/10 rhabdomyosarcomas, 15/19 leiomyosarcomas, and 9/9 desmoplastic melanomas. Nestin is more sensitive for MPNST than other neural markers and immunostains for nestin in combination with other markers could be useful in the diagnosis of MPNST. [source] Molecular tumor markers for asbestos-related mesothelioma: Serum diagnostic markersPATHOLOGY INTERNATIONAL, Issue 11 2006Masahiro Maeda Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30,40 years, and the prognosis is dismal. In addition to immunohistochemical markers, recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In contrast, the expression in renal carcinoma (ERC) gene has been discovered in the Eker rat model (Tsc2 gene mutant), which is a homolog of the human mesothelin/megakaryocyte potentiating factor gene, and a novel ELISA system (N-ERC/mesothelin) has been developed. It has also been found that N-ERC/mesothelin is very stable and plentiful in the blood. In the present paper the potential utility of molecular diagnostic markers is reviewed, including ELISA systems for asbestos-related mesothelioma. [source] Immunohistochemical analysis for histopathological subtypes in pediatric medulloblastomasPATHOLOGY INTERNATIONAL, Issue 2 2003Eun-Ik Son Medulloblastomas occurring in children represent a histological spectrum of varying anaplasia and nodularity. In order to determine whether immunohistochemical markers might be useful parameters in subclassifying these tumors, 17 pediatric medulloblastomas, including nine diffuse/non-anaplastic, four diffuse/anaplastic, three nodular/non-anaplastic and one nodular/anaplastic subtypes, were studied. In the present report, we investigate the expression of neural cell adhesion molecule (NCAM), nerve growth factor receptor (NGFR), neurofilament (NF), synaptophysin (SYN), glial fibrillary acidic protein (GFAP), S100, Bcl-2, and Ki-67 by using the immunohistochemistry against specific antibodies. This study showed that NGFR, NF, GFAP and S100 were not detected in anaplastic subtypes of medulloblastomas (0/5), while non-anaplastic subtypes were mainly expressed within the nodules. All 17 tumors were reactive for NCAM, SYN and Bcl-2. In addition, Ki-67 labeling indices for anaplastic subtypes (39.0 ± 7.42%) were significantly higher than that of non-anaplastic medulloblastomas (11.4 ± 8.04%; P < 0.0001). These results suggest that immunohistochemical markers are a useful adjunct in characterizing subtypes of pediatric medulloblastomas. [source] IDENTIFICATION OF MOLECULAR MARKERS IN DCIS RECURRENCEPATHOLOGY INTERNATIONAL, Issue 12 2001Provenzano E Background: DCIS represents preinvasive malignant change. With screening mammography DCIS has become a common entity. Its natural history is poorly understood and treatment remains controversial. Using a retrospective population based cohort, we have identified histological and molecular variables predictive of recurrence. Methods: All cases of DCIS reported in Victoria between 1988 and 1992 were entered into the Victorian Cancer Registry. In Situ and Small Cancer Register (ISSIBCR) and followed up annually regarding treatment, the event of recurrence and its nature and location. From this register a cohort of 66 DCIS lesions with subsequent recurrence as in situ or invasive disease were studied histologically, immunohistochemically and with CGH-based genetic analyses comparing them to a nested randomized control group of DCIS without recurrence matched for patient age and year of diagnosis. Recurrences have been analysed by the same techniques to compare them to the primary lesion. Results: 13 histological features were evaluated and lesion size, nuclear pleomorphism, cellular polarity, micropapillary architecture and central necrosis were all significant predictors of recurrence (p < 0.05). Immunohistochemistry showed p21 overexpression, bcl2 negativity and ERBB2 positivity to be markers of recurrence. In the case of ERBB2, positivity was a predictor of recurrence even when its overexpression was focal. Primary and recurrent DCIS lesions had similar morphological appearances, and grade of primary DCIS correlated with grade of subsequent invasive cancer. This morphological similarity was paralleled by similar protein expression and genomic changes in both in situ and invasive recurrences. Conclusion: We have identified histological and immunohistochemical markers of recurrence in DCIS, and shown similarities in morphology, protein expression and genetic changes between primary DCIS and its recurrence. [source] Proliferative and apoptotic differences between alveolar rhabdomyosarcoma subtypes: A comparative study of tumors containing PAX3-FKHR or PAX7-FKHR gene fusionsPEDIATRIC BLOOD & CANCER, Issue 2 2001Margaret H. Collins MD Abstract Background Most alveolar rhabdomyosarcomas (ARMS) have chromosome translocations and resultant gene fusion products. The more common translocation fuses the PAX3 and FKHR genes; patients who have PAX3-FKHR-positive ARMS have reduced event-free survival compared to patients with ARMS containing the less common translocation that fuses the PAX7 and FKHR genes. Procedure We examined histology, immunohistochemical markers of differentiation, and cell cycle characteristics of a panel of ARMS containing either PAX3-FKHR or PAX7-FKHR transcript to determine if these features differ between the ARMS subsets. Results Cell cycle parameters varied significantly: the number of nuclei that stained with either an immunohistochemical marker of proliferation (MIB1), or a TUNEL-based assay for apoptosis was significantly greater in tumors that expressed PAX3-FKHR compared to tumors that expressed PAX7-FKHR transcript. Conclusions We conclude that compared to PAX7-FKHR-containing tumors, ARMS that contain PAX3-FKHR transcript have (1) increased cell proliferation, consistent with greater loss of cell cycle regulation, and (2) apoptosis that is increased but insufficient to prevent tumor formation. More marked cell cycle dysregulation may contribute to poorer prognosis for patients with ARMS that have PAX3-FKHR fusion. Med Pediatr Oncol 2001;37:83,89. © 2001 Wiley-Liss, Inc. [source] |