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At least 433 records · Page 24Linked to original sources
PubMed2006

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Acid Phosphatase↗
PubMed2006

Construction and validation of tissue microarrays of ductal carcinoma in situ and terminal duct lobular units associated with invasive breast carcinoma.

Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of approximately 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, >or=50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

Breast Neoplasms↗
PubMed2005

Survivin expression in endometrial carcinoma: a tissue microarray study with correlation with PTEN and STAT-3.

Evasion of apoptotic cell death plays a key role in cancer development. Survivin is a member of the inhibitor of apoptosis proteins, which also has a role in the control of cell division. Survivin may be overexpressed in some tumors and has been suggested to be related to PTEN, beta-catenin, p53 [all of them frequently abnormal in endometrial carcinomas (ECs)], and STAT-3. A tissue microarray was constructed from paraffin-embedded blocks of 95 ECs, previously studied for microsatellite instability and for alterations in PTEN, k-RAS, and CTNNB-1. Immunohistochemical evaluation included 1) survivin, 2) markers of cell proliferation and apoptosis (Ki67-MIB1 and M 30-neoepitope cytokeratin 18), and 3) proteins involved in cell signaling pathways (PTEN, phospho-AKT, beta-catenin, p53, and STAT-3). Survivin expression was frequent in ECs (75.95%) but did not show any statistical significant correlation with histological type and grade, stage, overall survival, or mitotic and apoptotic indexes. Survivin expression had a statistical significant correlation with decreased PTEN expression (r = -0.383, p = 0.001), increased phospho-AKT (r = 0.70, p < 0.001), and positive STAT-3 immunostaining (r = 0.6, p < 0.001). Survivin expression did not show statistical correlation with either beta-catenin or p53 alterations. The results suggest that increased survivin expression is frequent in ECs and may be dependent on STAT-3 and PI3 K/AKT activation. Because PTEN abnormalities are very frequent in ECs, the results from this study indicate that PTEN may interfere with the process of apoptosis and cell proliferation by promoting survivin expression.

Apoptosis↗
PubMed2005

Skin metastases from unknown origin: role of immunohistochemistry in the evaluation of cutaneous metastases of carcinoma of unknown origin.

Determining the primary origin of skin metastases might be a challenging issue for pathologists, especially when there is no primary history or when this history is unavailable. The poor specificity of morphological appreciation is challenging, emphasizing the need for ancillary studies. We have retrieved 44 cases of skin metastases from our pathology files. Paraffin blocks were collected and homemade tissue arrays were made. We have tried to assess the primary origin based on morphological data alone, and then using 13 antibodies (cytokeratins (CK) 5/6, 7, 19, 20, thyroid transcription factor-1, carcinoembryonic antigen, PS100, tumor-associated glycoprotein 72, BerEP4, estrogen receptor (ER), progesterone receptor (PR), CD10, and E-cadherin). Most metastases in our series were from breast (13) and colorectal cancers (six) as they are the main clinical activity in our hospital. Only 44% of cases were correctly assessed based on the sole morphology, emphasizing the need for ancillary studies. CK 20, ER, and PR were the most helpful markers to determine the primary origin of skin metastases by highlighting colorectal origin and mammary origin, respectively. By far, clinical information and morphological evaluation are more reliable than the use of ancillary techniques, which have to be used in the absence of the former one and the poor differentiation of the latter ones. Azoulay S, Adem C, Le Pelletier F, Barete S, Francès C, Capron F. Skin metastases from unknown origin: role of immunohistochemistry in the evaluation of cutaneous metastases of carcinoma of unknown origin.

Adenocarcinoma↗
PubMed2006

Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features.

Protein gene product 9.5 (PGP9.5) is a neurospecific peptide that removes ubiquitin from ubiquitinated proteins and prevents them being targeted for degradation by proteosomes. Its expression is a potential marker of non-small lung cancer, invasive colorectal cancer and esophageal squamous cell carcinoma. Gallbladder (GB) cancer is the most common malignant tumor of the biliary tract and is usually associated with gallstone disease, a late diagnosis, unsatisfactory treatment and a poor prognosis. To understand the role of PGP9.5 in GB cancer, we examined the methylation status of its promoter and its expression in surgical biopsy samples. Formalin-fixed, paraffin-embedded tumors and non-neoplastic GB tissues (22 carcinomas, eight adenomas, 26 normal epithelia) were collected from patients who had undergone surgical resection. The methylation status of the promoter region of the PGP9.5 gene was determined by methylation-specific polymerase chain reaction, and the expression of PGP9.5 was examined by immunohistochemistry using tissue microarrays. PGP9.5 promoter was methylated in 84.6% (22/26) of normal GB epithelium, 37.5% (3/8) of adenomas and 27.2% (6/22) of carcinomas. Most tumors with an unmethylated promoter exhibited positive staining for PGP9.5 in epithelial and neoplastic cells, but no PGP9.5 expression was observed in normal epithelia or in tumor tissues with a methylated promoter. No correlation was found between promoter hypomethylation of PGP9.5 and clinicopathological findings (i.e. age, sex, histological type or grade, N-status, invasion depth or tumor stage) whereas PGP9.5 hypomethylation was found to be inversely correlated with the presence of a gallstone (P = 0.015). These results suggest that PGP9.5 promoter hypomethylation could be a reliable marker for GB cancer and that DNA hypomethylation might play an important role in re-expression of the PGP9.5 gene in GB cancer.

Adenocarcinoma↗
PubMed2004

Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue microarray.

AIMS: In some cases distinction between chromophobe renal cell carcinoma (CRCC), oncocytoma and clear cell (conventional) renal cell carcinoma (eosinophilic variant) using routine light microscopy remains problematic. The present study investigates the level of agreement in the diagnosis of CRCC, as well as the histological features most frequently used for this diagnosis by two pathologists with a special interest in renal neoplasia. The sensitivity and specificity of immunohistochemical markers in cases with overlapping histological features in the diagnosis of CRCC were also studied. Electron microscopy was performed, as a diagnostic gold standard, on all of the cases. METHODS AND RESULTS: Thirty-two renal tumours with predominantly eosinophilic cytoplasm were reviewed in a blinded fashion by two pathologists. The diagnosis and morphological features used to render each diagnosis were tabulated. Validation of the utility of keratin 7 and 20, epithelial membrane antigen (EMA), vimentin, CD10, parvalbumin, RCC antigen, antimitochondrial antibody and Hale's colloidal iron was performed by the construction of a tissue microarray (TMA) master block. Based on histological criteria alone, overall agreement on the diagnosis of these tumours was reached in 69% of the cases, while there was total disagreement in 12%. In 59% of the cases, total agreement was reached in classifying the case as a CRCC based on histology alone. Kappa statistics for interobserver variability were calculated as only slight agreement (kappa = 0.3). The histological features most frequently associated with a diagnosis of CRCC were accentuated cell borders (87%) and a combination of hyperchromatic wrinkled nuclei (79%) and perinuclear halos (74%). The most sensitive and specific marker for CRCC was parvalbumin (sensitivity 0.91; specificity 1.0). The immunohistochemical profile of EMA+/ vimentin- was useful but had low specificity (sensitivity 0.75; specificity 0.4). CD10 had the highest sensitivity (1.0) but worst specificity (0.25) for CRCC. Keratin 7 had high sensitivity (0.83) but fairly low specificity (0.37) for CRCC. Hale's colloidal iron and the RCC antigen marker were not contributory. Finally, the antimitochondrial antibody was found to be fairly sensitive (0.83) for excluding CRCC. CONCLUSIONS: A small but significant proportion of renal tumours with cells having eosinophilic cytoplasm cannot be classified, even by experienced pathologists, based on histology alone. In these cases it is imperative to use markers with known sensitivity and specificity for the diagnosis of CRCC.

Adenoma, Oxyphilic↗
PubMed2005

Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers.

AIMS: To survey the expression of members of the S100 family of calcium-binding proteins in normal human tissues and common cancers using tissue microarrays. S100A6, S100A8, S100A9 and S100A11 have all been suggested to have potential roles in carcinogenesis and tumour progression but their expression has not been described in a wide range of human tissues and tumours. METHODS AND RESULTS: A custom-made tissue array, containing 291 tissue cores representing 28 tissue types and 21 tumour types, was used to produce sections that were immunostained for S100A2, S100A6, S100A8, S100A9, S100A11, calbindin 1, calbindin 2, S100B and parvalbumin. S100A6, S100A8 and S100A9 were expressed in 32%, 12% and 28% of breast cancers, respectively. There was a translocation of S100A11 expression from exclusively nuclear in normal tissues to cytoplasmic and nuclear in all common cancers. CONCLUSIONS: S100A6, S100A8, S100A9 and S100A11 are all expressed in common cancers, especially breast cancer. In addition, S100A11 undergoes a nucleocytoplasmic translocation which may have a direct influence on the proliferation of the cancer cells.

Calbindin 1↗
PubMed2005

Characterization of macrophage subpopulations in colon cancer using tissue microarrays.

AIMS: To determine the pattern of macrophage infiltration in colon cancers and its correlation with clinicopathological characteristics. METHODS AND RESULTS: Colon cancers from 100 patients were arrayed into a tissue microarray (TMA). Four cores per tumour were taken: three from the invasion front (IF) and one from the tumour surface (TS). Macrophages were quantified by immunohistochemistry with antibodies to the PG-M1, KP-1, MRP8, MRP14 and MRP8/14 antigens. The number of macrophages was significantly higher in the TS cores than in the IF cores and both tumour sites showed a higher number of macrophages than the normal mucosa. The number of macrophages decreased in higher stage tumours. The different tumour-associated macrophage (TAM) subpopulations were positively correlated with each other. CONCLUSIONS: The increased number of macrophages in cancers compared with normal colon mucosa indicates that macrophages are attracted to the tumour site. However, decreasing macrophages in higher stage colon cancers suggest that this attraction decreases with tumour progression.

Aged↗
PubMed2006

Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma.

AIMS: Glypican 3 (GPC3) is a cell surface heparan sulphate proteoglycan expressed specifically in the fetal liver and malignant neoplasms of hepatocyte lineage. The aim was to evaluate the significance of GPC3 in alpha-fetoprotein (AFP)-producing gastric carcinoma (GC) and other forms of GC. METHODS AND RESULTS: We immunohistochemically evaluated GPC3 expression in representative cases of AFP-producing GC and in a tissue microarray of a consecutive series of GCs with other markers of hepatocyte lineage (AFP, PIVKA-II and hepatocyte antigen, HEP). In a series of 10 cases of AFP-producing GC, we observed immunohistochemical positivity for GPC3, PIVKA-II and HEP in 10, three and three cases in components with a hepatoid pattern and in nine, two and five cases in components with a non-hepatoid pattern, respectively. In a series of 118 cases of GC, we observed positivity for AFP, GPC3, PIVKA-II and HEP in one (0.8%), four (3.4%), six (5.1%) and 26 cases (22%), respectively. GPC3 was observed concurrently with AFP and discordantly with PIVKA-II and HEP. GPC3 positivity was clearly stronger in a larger area compared with immunoreactivity for AFP. CONCLUSIONS: GPC3 is a sensitive marker for AFP-producing GC and its hepatoid component and is therefore useful to identify this aggressive subgroup of GC.

Adenocarcinoma↗
PubMed2006

ES1, a new lung carcinoma antibody--an immunohistochemical study.

AIMS: To characterize a single domain antibody (sdAb), AFAI, obtained by panning a naive phage display library of single domain antibodies against the non-small cell lung carcinoma cell line A549. AFAI recognizes a variant form of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6 or CEA6). METHODS AND RESULTS: Various normal tissues and 139 neoplastic lesions from lung and other organs were immunostained with ES1 antibody, a pentameric and highly avid form of AFAI. ES1 was immunoreactive with 34 of 35 non-squamous large cell lung carcinomas with staining intensities ranging from focal to extensive and from moderate to strong. Importantly, ES1 stained poorly differentiated lung adenocarcinomas and many undifferentiated large cell lung carcinomas that typically show negative immunoreactivity with an antibody specific for thyroid transcription factor-1. Non-lung adenocarcinomas showed more focal and weaker immunoreactivity than for lung adenocarcinoma. Other carcinomas showed negative or weak immunoreactivity and normal tissues showed no immunoreactivity. CONCLUSIONS: Compared with other antibodies used in the clinical evaluation of lung adenocarcinomas, ES1 is more lung carcinoma sensitive, more sensitive in immunostaining of poorly differentiated adenocarcinomas that are usually associated with distant metastasis and less immunoreactive with normal tissues.

Antibodies, Neoplasm↗
PubMed2006

Characterization of the 12C4 survivin monoclonal antibody and insight into the expression of survivin in human adult tissues.

AIMS: To elucidate the expression and regulation of survivin in normal tissues. METHODS AND RESULTS: A novel monoclonal antibody (12C4) to survivin was generated. Application of this antibody to determine survivin expression in human normal adult tissues revealed that most adult tissues do not express survivin and, where it is present, survivin is largely restricted to a small subset of epithelial cells and cells with proliferative potential such as thymus. Survivin expression among positive tissues showed individual variations, ranging from zero to < 5% positive cells in epithelial cell populations. Testis is the only human adult tissue highly expressing survivin, with 60-70% positivity in the nuclei of spermatogonia. Consistent with deregulated expression of survivin associated with oncogenesis, we found that certain ligands and transcription factors differentially modulate survivin promoter activity in cancer cells versus normal/untransformed cells. CONCLUSION: Deregulation of survivin transcription controls in individual epithelial cells may contribute to oncogenesis in various human adult tissues.

Adult↗
PubMed2006

Health status of transgenic pigs expressing the human complement regulatory protein CD59.

BACKGROUND: Microinjection of foreign DNA into pronuclei of zygotes has been the method of choice for the production of transgenic domestic animals. Following microinjection the transgene is randomly integrated into the host genome which can be associated with insertional mutagenesis and unwanted pathological side effects. METHODS: Here, we evaluated the health status of pigs transgenic for the human regulator of complement activation (RCA) CD59 and conducted a complete pathomorphological examination on 19 RCA transgenic pigs at 1 to 32 months of age from nine transgenic lines. Nine wild-type animals served as controls. Expression levels of human complement regulator CD59 (hCD59) mRNA were measured by RT-PCR and distribution of hCD59 protein was determined by immunohistochemistry. RESULTS: Albeit variable transgene expression levels, no specific pathomorphologic phenotype associated with the presence of the transgene in all analyzed pig lines could be detected. CONCLUSIONS: Transgenic expression of this human RCA gene construct is not correlated with a specific pathological phenotype in pigs. This is crucial for the application of the technology and the use of transgenic pigs for biomedical and agricultural applications.

Animals↗
PubMed2006

Immunohistochemical expression of aminopeptidase N (CD13) in human lung squamous cell carcinomas, with special reference to Bestatin adjuvant therapy.

Bestatin, a specific inhibitor of aminopeptidase N (CD13), has been reported to prolong survival time in patients with completely resected stage I lung squamous cell carcinoma. Considering the antitumor mechanism of Bestatin, it is interesting to know whether CD13 is expressed in human lung squamous cell carcinoma. The immunohistochemical expression of CD13 was examined in human lung carcinoma and the question of whether CD13 was immunohistochemically expressed in the interstitial tissue was investigated, mainly in the fibroblasts and blood vessels, surrounding the tumor nests of various kinds of non-small cell lung cancers, especially of squamous cell carcinomas. In Japanese squamous cell carcinoma of the lung, 38 (61.3%) out of 62 cancers were positively stained in the same manner on immunohistochemistry for CD13. The area of interstitial tissue positively stained for CD13 varied depending on the case. To confirm the cell nature of the interstitial tissue with CD13 positivity, double immunohistochemistry using CD34 and alpha-smooth muscle actin was performed. Double immunohistochemistry showed that the majority of CD13-positive cells were slender fibroblastic cells around the blood vessels and some endothelial cells.

Adjuvants, Immunologic↗
PubMed2006

Organ-specific endoglin (CD105) expression in the angiogenesis of human cancers.

Some markers of angiogenic endothelial cells are emerging as targets for cancer therapy. The present study compared the expression of CD105 with that of other endothelial markers in cancers from various organs. Surgically resected cancer tissues from 188 patients comprising brain (n = 17), lung (n = 38), breast (n = 30), stomach (n = 30), colon (n = 31), liver (n = 32), and kidney (n = 10) cancers were immunohistochemically analyzed on tissue microarrays using a panel of eight endothelial markers. CD31 was expressed in vascular endothelial cells in cancer lesions as well as in non-cancerous areas (30-100%) in all core tissue samples. CD105 expression was intense and restricted to capillary endothelial cells in cancer lesions (>73%). In contrast, positive expression of CD105 was seen in <20% of non-cancerous areas in the same organs. However, no significant difference in CD105 expression in vascular endothelial cells between cancer lesions and non-cancerous areas from liver and renal cancer samples was found. Vascular endothelial growth factor (VEGF), Flt1, and Flk1 were also expressed, but only sporadically and in few samples (<30%), and transforming growth factor (TGF)-beta1 and TGF-betaRII were negative in vascular endothelial cells but generally positive in cancer cells. CD44 was strongly expressed in sinusoidal endothelial cells of the liver (90-100%). These results show that CD105 is expressed specifically in the tumor angiogenesis of brain, lung, breast, stomach, and colon cancers.

Adult↗
PubMedDate not supplied

Relationship between p53-associated proteins and estrogen receptor status in ovarian serous neoplasms.

We studied the immunoexpression of p14ARF, MDM2, and p53, in addition to relationships between those protein expressions and estrogen receptor (ER)alpha in ovarian serous tumors including benign (n= 23), borderline (n= 41), and malignant (n= 94). The aberrant expressions of p14ARF, MDM2, and p53 were observed in 19.6% (31/158), 47.5% (75/158), and 39.9% (63/158) of cases, respectively. The expression of MDM2 was significantly higher in borderline tumors compared to benign (P= 0.04) and malignant (P < 0.01) tumors. p53 expression in borderline tumors was uncommon, and p14ARF expression loss was mainly observed in carcinomas. Altered expression of p14ARF, MDM2, and p53 shows significant relationship with stage. Overexpression of MDM2 (P= 0.01) and loss of p14ARF expression (P= 0.04) were significantly associated with ER expression. Our results suggest that alteration of p14ARF-MDM2-p53 pathway proteins may contribute significantly to the tumorigenesis of ovarian serous neoplasms, and ER is involved in cellular regulation of p14ARF-MDM2-p53 pathway in ovarian serous neoplasms.

Adolescent↗
PubMedDate not supplied

Tissue arrays as fiducial markers for section alignment in 3-D reconstruction technology.

Combination of conventional histology and the three-dimensional spatial view of tissue structures offers new prospects for understanding and diagnosing nature and development of human diseases. The essential technical problem related to three-dimensional reconstruction in histopathology is represented by the correct alignment of serial sections. During the past years several methods have been proposed but failed to become popular because of their limits in terms of time consume and restricted applicability. We aimed to overcome this problem by applying the technology of Tissue Array, thus by positioning adequate fiducial markers from specific "donor" blocks into the "recipient" paraffin block of interest. Digitized pictures of serially cut sections were aligned according to the tissue markers embedded by Tissue Array, and then processed with specific softwares for three-dimensional reconstruction. Thirteen models, including fetal hearts, breast and thyroid carcinomas, were elaborated. We found the procedure to be easy, fast and reproducible. Moreover, by selectively embedding the fiducial markers according to specific angles, the Tissue Arrays can be exploited in order to establish the distance between sections. This original methodology of incorporating Tissue Arrays into paraffin blocks as fiducial markers for three-dimensional reconstruction has a potential impact on histology for research purposes and diagnostic applications.

Algorithms↗