Gulsah Kaygusuz

Placental S100 (S100p) and GATA3 : Markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray

The morphologic distinction between prostate and urothelial carcinoma can be difficult. To identify novel diagnostic markers that may aid in the differential diagnosis of prostate versus urothelial carcinoma, we analyzed expression patterns in prostate and bladder cancer tissues using complementary DNA microarrays. Together with our prior studies on renal neoplasms and normal kidney, these studies suggested that the gene for placental S100 (S100P) is specifically expressed in benign and malignant urothelial cells. Using tissue microarrays, a polyclonal antiserum against S100P protein stained 86% of 295 urothelial carcinomas while only 3% of 260 prostatic adenocarcinomas and 1% of 133 renal cell carcinomas stained. A commercially available monoclonal antibody against S100P stained 78% of 300 urothelial carcinomas while only 2% of 256 prostatic adenocarcinomas and none of 137 renal cell carcinomas stained. A second gene, GATA3, also showed high level expression in urothelial tumors by cDNA array. A commercially available monoclonal antibody against GATA3 stained 67% of 308 urothelial carcinomas, but none of the prostate or renal carcinomas. For comparison, staining was also performed for p63 and cytokeratin 5/6. p63 stained 87% of urothelial carcinomas whereas CK5/6 stained 54%. Importantly, when S100P and p63 were combined 95% of urothelial carcinomas were labeled by one or both markers. We conclude that the detection of S100P and GATA3 protein expression may help distinguish urothelial carcinomas from other genitourinary neoplasms that enter into the differential diagnosis.

A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis.

Prostate cancer is the most commonly diagnosed cancer among men in the United States. Recently, fusion of TMPRSS2 with ETS family oncogenic transcription factors has been identified as a common molecular alteration in prostate cancer, where most often the rearrangement places ERG under the androgen-regulated transcriptional control of TMPRSS2. Here, we carried out rapid amplification of cDNA ends (RACE) on a prostate cancer specimen carrying an atypical aberration discovered by array-based comparative genomic hybridization (array CGH), suggesting an alternative fusion partner of ERG. We identified novel transcribed sequences fused to ERG, mapping 4 kb upstream of the TMPRSS2 start site. The sequences derive from an apparent second TMPRSS2 isoform, which we found also expressed in some prostate tumors, suggesting similar androgen-regulated control. In a reverse transcription-polymerase chain reaction (RT-PCR)-based survey of 63 prostate tumor specimens (54 primary and nine lymph node metastases), 44 (70%) cases expressed either the known or novel variant TMPRSS2-ERG fusion, 28 (44%) expressed both, 10 (16%) expressed only the known, and notably six (10%) expressed only the variant isoform fusion. In this specimen set, the presence of a TMPRSS2-ERG fusion showed no statistical association with tumor stage, Gleason grade or recurrence-free survival. Nonetheless, the discovery of a novel variant TMPRSS2 isoform-ERG fusion adds to the characterization of ETS-family rearrangements in prostate cancer, and has important implications for the accurate molecular diagnosis of TMPRSS2-ETS fusions.

Antibacterial effects of electrically activated vertebral implants.

Bio-implants in the human body act as passive surfaces that are prone to bacterial adhesion potentially leading to deep body infections. Pedicle screws made of uncoated or silver-coated titanium alloy were used both in vitro and in vivo to determine whether silver-coated materials have antimicrobial properties when they are anodized. Twenty-four New Zealand Albino rabbits were divided into four groups with six in each. In Group 1, the rabbits were exposed to 8 muA direct current (DC) via silver-coated screws. In Group 2, the rabbits were not exposed to any electrical current, but silver-coated screws were used. In Group 3, the rabbits were exposed to 8 muA DC using uncoated screws. In Group 4, the rabbits were not exposed to any electrical current, but uncoated screws were used. Staphylococcus aureus (106 cfu) was inoculated into the rabbits before any electrical current was applied. All the animals were killed, and the areas surrounding the screws were histologically and microbiologically examined. Silver-coated titanium screws prevented implant-associated deep bone infections when they were polarized anodically. The antibacterial effects of the same screws with the same bacterium were confirmed in in vitro experiments on agar plates. When the screws were anodized with the same electrical parameters in vitro, a marked inhibition zone was detected around the silver-coated screws but not around the uncoated screws. Our findings suggest that silver-coated titanium implants can be used to prevent implant-associated deep bone infections when they are polarized anodically.

The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma.

It can be difficult to differentiate hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA). An appropriate immunohistochemical panel is required for the differential diagnosis. This study aimed at finding the best panel, including hepatocyte-specific antigen (Hepatocyte), pCEA, CD10, Villin, CD34, TTF-1, MOC-31, CK7, and CK20 antibodies. Sixty-eight cases of HCC and 107 cases of MA were investigated. Hepatocyte positivity was seen in 95.6% of HCCs and in 1.9% of MAs. pCEA was expressed in 47.8% of HCCs and in 86.8% of MAs. CD10 stained 73.13% of HCCs and 36.9% of MAs. Villin was positive in 23.5% of HCCs and in 81.0% of MAs. Canalicular staining with pCEA, CD10, and Villin was seen only in HCCs. Sinusoidal CD34 staining was seen only in 42.6% of HCCs. A small subset of HCCs demonstrated cytoplasmic TTF-1 and MOC-31. CK7 was expressed in 29.4% of HCCs and in 29.9% of MAs, whereas CK20 stained 14.7% of HCCs and 62.6% of MAs. In conclusion, Hepatocyte should be combined with pCEA, MOC-31, CD10, and CD34. Canalicular staining with pCEA, CD10, and Villin is specific for HCC. CK7 and CK20 expression may be seen in some HCCs. We suggest that the best panel for discriminating HCC from MA should contain Hepatocyte, MOC-31, pCEA, CD10, and CD34.

Microvessel density and regulators of angiogenesis in malignant and nonmalignant prostate tissue.

The aim of this study was to investigate the relationship between microvessel density (MVD), positive and negative angiogenic factors, and established prognostic factors in prostate cancer (PC), and, to clarify the effect of angiogenic factors to angiogenesis. The vascularization of neoplastic, non-neoplastic prostate tissue was determined by CD34 immunostaining. Angiogenetic mediators VEGF, bFGF, TSP-1, and p53 were studied by immunohistochemistry. Neovascularization and p53, VEGF, and TSP-1 expressions of tumorous tissue were higher than non-tumorous tissue.The bFGF expression in these tissues was not different.The p53 expression was not correlated with the expressions of VEGF, bFGF, and TSP-1 in PC. Our results demonstrate a significant increase in MVD, VEGF, TSP-1, and p53 expressions in prostate tumorigenesis. The pretreatment sPSA was the only parameter demonstrating significant correlation with tumor grade and may have a value in the prediction of aggressive tumor behavior in PC.

The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms

PAX5 is a B-cell transcription factor whose expression at the protein level is reliably detected by immunohistochemistry in routine biopsies. The purpose of this study was to investigate whether PAX5 immunohistochemistry has diagnostic benefit as a B-cell marker in the work-up of undifferentiated malignant neoplasms. Twenty-five cases previously diagnosed as undifferentiated malignant neoplasms were selected. In addition, 59 hematolymphoid and 884 non-hematolymphoid malignancies were studied such that the specificity of PAX5 immunohistochemistry could be addressed. Two of the 25 (8%) undifferentiated neoplasms showed diffuse staining for PAX5, which indicated a B-cell derivation for these neoplasms that was not appreciated at the time of initial diagnosis. PAX5 staining was detected in the vast majority of hematolymphoid tumors of B-cell derivation but only in 5 of 884 (less than 1%) non-hematolymphoid tumors. Our results further show that PAX5 may be the only detectable marker of B lineage in lymphomas that lack or show equivocal CD45RB and CD20 expression. We conclude that the addition of PAX5 to a panel of immunohistologic markers used in the interrogation of undifferentiated neoplasms is of diagnostic benefit. Its expression can also facilitate the diagnosis of classical and nodular lymphocyte-predominant Hodgkin lymphoma with atypical morphologic and immunohistologic features. Lastly, we have shown that the lack of its expression at the protein level in many epithelial and mesenchymal neoplasms renders PAX5 expression an extremely specific marker of the B lineage.

Intra-articular epithelioid sarcoma showing mixed classic and proximal-type features: report of 2 cases, with immunohistochemical and molecular cytogenetic INI-1 study.

Epithelioid sarcoma, a rare sarcoma with epithelial differentiation, most often occurs in the distal extremities; however, it may occur in essentially any location. With the recent recognition that the loss of expression of the tumor-suppressor gene INI-1 may be associated with epithelioid sarcoma, it has become clear that epithelioid sarcoma may occur in previously unsuspected locations such as bone. Only 2 cases of intra-articular epithelioid sarcoma have been previously reported. We retrieved 2 intra-articular cases coded as epithelioid sarcoma from our archives. Both expressed cytokeratins (AE1/AE3 and OSCAR), CD34, vimentin, and epithelial membrane antigen, and showed complete loss of expression of INI-1. Fluorescence in situ hybridization was performed on formalin-fixed, paraffin-embedded sections by using a laboratory-developed dual-color probe containing INI1 (CTD-2511E13 and CTD-2034E7) (22q11.2) (OR) and PANX2 (RPCI3-402G11) (22q13.33) (GR) probes as control. Both cases occurred in a clearly intra-articular location in the knee. Case 1 was that of a 19-year-old man with a long-standing history of pain and limited joint function. This patient was disease free after amputation. Case 2 was that of a 60-year-old woman. Follow-up information available for this patient showed bilateral subpleural metastases. Morphologically, case 1 showed features of proximal-type epithelioid sarcoma, whereas case 2 showed mixed features of classic and proximal-type epithelioid sarcoma. Immunohistochemistry showed complete loss of INI-1 protein in both cases; fluorescence in situ hybridization analyses were negative for INI-1 gene deletion. Herein, we have reported 2 cases of intra-articular epithelioid sarcoma, showing morphologic and immunohistochemical features identical to those of epithelioid sarcoma in conventional locations, including loss of INI-1 expression. Intra-articular epithelioid sarcoma should be distinguished from malignant pigmented villonodular synovitis and from carcinoma metastatic to the synovium. Improved recognition of this rare clinical presentation should allow for better understanding of its unique features.

Vitiligo associated with malignant melanoma and lupus erythematosus.

There exists several reports where malignant melanoma is associated with vitiligo, vitiligo with discoid lupus erythematosus and lupus erythematosus with urticaria. 1–6 However, there are no reports in which vitiligo, malignant melanoma, lupus erythematosus and urticaria coexist in the same case. Herein, we report a case of a patient who developed lupus erythematosus, malignant melanoma, vitiligo and urticaria simultaneously.

Myeloid sarcomas: a clinicopathologic study of 20 cases.

Objective: Myeloid sarcoma is a tumoral mass of mature or immature myeloid blasts in extramedullary anatomic locations. It can be seen de novo or in association with acute myeloid leukemia, myeloproliferative neoplasias, or myelodysplastic syndrome. Isolated myeloid sarcoma can be seen as a relapse in cases with allogenic bone marrow transplantation. Although it may involve any tissue in the body, the most common locations are skin, soft tissues, lymph nodes, and the gastrointestinal tract. Immunohistochemically, most cases show myelomonocytic or pure monoblastic differentiation. We reviewed the clinicopathological features of 20 cases of myeloid sarcoma diagnosed in our institute in view of the literature. Materials and Methods: The cases diagnosed between 2005 and 2012 at the Ankara University Faculty of Medicine, Department of Pathology, were selected. Clinicopathological findings including the age and sex of the patients; symptoms; anatomic location; accompanying hematological disease; and the morphological, immunohistochemical, and cytogenetic features of the cases were noted. Results: Sixteen of the patients were male and 4 were female. The median age at diagnosis was 47 years. The most commonly involved locations were the lymph nodes and skin. Immunohistochemically, eleven cases were of the myelomonocytic and 7 cases were of the myeloid phenotype, whereas 2 cases showed pure monoblastic differentiation. The median follow-up period for the 18 cases with known clinical data was 33 weeks. Five patients died of the disease in an average of 36 weeks. Conclusion: Myeloid sarcoma is a rare presentation of leukemias, myeloproliferative neoplasias, or myelodysplastic syndrome, composed of immature myelomonocytic cells in extramedullary tissues. It may present with variable morphological and phenotypic features, always creating a challenge in pathological diagnosis.

Miliary brain metastases from occult lung adenocarcinoma: Radiologic and histopathologic confirmation.

“Miliary brain metastases”, also termed as “Carcinomatous encephalitis”, are an extremely rare form of cerebral metastasis. Here in this article, we report a 52 year-old male patient with miliary brain metastases originating from occult lung adenocarcinoma. There were no significant findings on his initial physical and neurological examinations except limited cooperation. Brain computed tomography revealed edematous regions at the inferior sections of both parietal lobes. Then after, the contrast-enhanced magnetic resonance imaging revealed innumerable multi-dimensional lesions associated with surrounding edema on T2-weighted images. The proton magnetic resonance spectroscopy revealed increases in the choline and lipid peaks with decreased N-acetylaspartate in a similar manner with metastatic brain tumors. Histopathological findings pointed out that malignant epithelial tumor metastasis were originating in primary lung adenocarcinoma. Despite the advances in technical equipments and medical knowledge, miliary metastatic brain tumors are quite rare and the differential diagnosis is difficult. Our aim in this article was to present this rare case in which the lung was thought to be the primary focus; and outline the radiological characteristics. Also, we believe that the findings presented by proton magnetic resonance spectroscopy may contribute to making a differential diagnosis.