Lee Ann Baldridge

University of Verona, Verona, Veneto, Italy

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Publications (44)194.11 Total impact

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    ABSTRACT: Renal cell carcinoma (RCC) is known for its ability to metastasize synchronously or metachronously to various anatomic sites. Distinguishing histologic subtypes of metastatic RCC has become increasingly important, as prognosis and therapy can differ dramatically between subtypes. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping metastatic RCC in light of these potential therapeutic implications. Specimens from 103 cases of metastatic RCC were retrieved, including 32 cases originally diagnosed as metastatic clear cell renal cell carcinoma (CCRCC), 8 as metastatic papillary renal cell carcinoma (PRCC), and 63 metastatic RCC without a specific subtype. Immunohistochemistry was performed with antibodies against cytokeratin 7 (CK7) and alpha-methylacyl-CoA racemase (AMACR). Dual color interphase fluorescence in situ hybridization was utilized to assess for deletion of chromosome 3p and trisomy of chromosomes 7 and 17 in all tumors. Chromosome 3p deletion was detected in 41% of all metastatic RCC specimens, and trisomy of chromosomes 7 and/or 17 was detected in 16%. Of metastatic CCRCC, chromosome 3p deletion was detected in 63%. Of metastatic PRCC, 75% showed trisomy of chromosomes 7 and/or 17. Of the tumors not previously classified, 6% were positive for CK7, and 64% were positive for AMACR; 35% showed chromosome 3p deletion, and 16% showed trisomy of chromosomes 7 and/or 17. Combined analysis of immunohistochemistry and cytogenetics enabled reclassification of 52% of these metastatic tumors not previously classified. Our findings support the utility of immunohistochemistry and cytogenetics for subtyping metastatic RCC.
    Molecular Cancer 02/2014; 13(1):39. · 5.13 Impact Factor
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    ABSTRACT: Atypical adenomatous hyperplasia (AAH) is a distinct entity in prostate pathology, defined as a well-circumscribed lobule of closely packed crowded small glands or acini. Although it has been proposed as a precursor lesion to prostate cancer, the biological nature of AAH is currently uncertain. The TMPRSS2-ERG fusion gene is a common recurrent chromosomal rearrangement in prostate cancer and in its precursor lesion, prostatic intraepithelial neoplasia. The prevalence of TMPRSS2-ERG alteration in AAH is unknown. Fifty-five separate prostate specimens containing AAH were investigated by fluorescence in situ hybridization and immunohistochemistry for TMPRSS2-ERG rearrangement. TMPRSS2-ERG rearrangements were not identified in AAH either by fluorescence in situ hybridization or by immunohistochemistry.
    The American journal of surgical pathology 07/2013; · 4.06 Impact Factor
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    ABSTRACT: Small cell carcinoma of the prostate is both morphologically and immunohistochemically similar to small cell carcinoma of other organs such as the urinary bladder or lung. TMPRSS2-ERG gene fusion appears to be a highly specific alteration in prostatic carcinoma that is frequently shared by small cell carcinoma. In adenocarcinoma, immunohistochemistry for the ERG protein product has been reported to correlate well with the presence of the gene fusion, although in prostatic small cell carcinoma, this relationship is not completely understood. We evaluated 54 cases of small cell carcinoma of the prostate and compared TMPRSS2-ERG gene fusion status by fluorescence in situ hybridization (FISH) to immunohistochemical staining with antibody to ERG. Of 54 cases of prostatic small cell carcinoma, 26 (48%) were positive for TMPRSS2-ERG gene fusion by FISH and 12 (22%) showed overexpression of ERG protein by immunohistochemistry. Of the 26 cases positive by FISH, 11 were also positive for ERG protein by immunohistochemistry. One tumor was positive by immunohistochemistry but negative by FISH. Urinary bladder small cell carcinoma (n = 25) showed negative results by both methods; however, 2 of 14 small cell carcinomas of other organs (lung, head, and neck) showed positive immunohistochemistry but negative FISH. Positive staining for ERG by immunohistochemistry is present in a subset of prostatic small cell carcinomas and correlates with the presence of TMPRSS2-ERG gene fusion. Therefore, it may be useful in confirming prostatic origin when molecular testing is not accessible. However, sensitivity and specificity of ERG immunohistochemistry in small cell carcinoma are decreased compared to FISH.
    Human pathology 07/2013; · 3.03 Impact Factor
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    ABSTRACT: Urinary bladder squamous cell carcinoma and urothelial carcinoma with squamous differentiation are often high-grade and high-stage tumors that are thought to be associated with a poorer prognosis and response to therapy compared with urothelial carcinoma without divergent differentiation. Therefore, recognition of a squamous component is increasingly important in guiding prognosis and therapy. We investigated the expression of MAC387, desmoglein-3, and TRIM29 in pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation to determine whether they have utility as diagnostic biomarkers for squamous differentiation. Eighty-four cases were retrieved from participating institutions including 51 pure urinary bladder squamous cell carcinomas and 33 urothelial carcinomas with squamous differentiation. MAC387, desmoglein-3, and TRIM29 antibodies demonstrated positive staining in pure squamous cell carcinoma in 51 (100%), 46 (90%), and 48 (93%) cases, respectively. Urothelial carcinoma with squamous differentiation showed reactivity for MAC387, desmoglein-3, and TRIM29 in the squamous component for 32 (97%), 26 (79%), and 32 (97%) cases, respectively. MAC387 demonstrated a sensitivity of 99% and a specificity of 70% for squamous differentiation, whereas desmoglein-3 yielded a sensitivity of 86% and a specificity of 91%. No urothelial component showed greater than 10% labeling for desmoglein-3. TRIM29 labeling showed a sensitivity of 95%, but a poorer specificity of 33%. In summary, MAC387 and desmoglein-3 are reliable diagnostic markers for supporting the morphologic impression of squamous differentiation in urinary bladder carcinoma. Desmoglein-3 shows high specificity, whereas TRIM29 was most likely to demonstrate labeling in areas without light microscopically recognizable squamous differentiation.
    Human pathology 06/2013; · 3.03 Impact Factor
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    ABSTRACT: Clear cell papillary renal cell carcinoma (CCPRCC) shares morphologic overlap with clear cell renal cell carcinoma, although it lacks chromosome 3p and VHL gene abnormalities. Rare cases have been reported in von Hippel-Lindau (VHL) patients (germline mutation of the VHL gene), the significance of which is uncertain. We analyzed morphologic, immunohistochemical, and molecular features in 14 CCPRCC-like tumors and 13 clear cell renal cell carcinomas from 12 patients with VHL disease. Gross appearance of CCPRCC-like tumors ranged from yellow-orange to tan, red-brown, or extensively cystic. Histologic features included: small papillary tufts (79%), branched tubules (71%), branched papillae (64%), flattened peripheral cysts (64%), and apically aligned nuclei (43%). Almost all CCPRCC-like tumors (82%) lacked the characteristic immunoprofile of sporadic CCPRCC (CK7, CAIX, CD10, AMACR), often showing diffuse CD10 labeling (64%), negative or focal CK7 reactivity (55%), or both (18%). Three tumors (27%) showed strong AMACR staining. Chromosome 3p deletion was often present (82%), similar to that observed in clear cell renal cell carcinomas (80%); no CCPRCC-like tumor had chromosome 7 or 17 abnormalities. In summary, tumors that histologically resemble CCPRCC sometimes occur in patients with VHL disease but usually lack the characteristic immunohistochemical and molecular profile, suggesting that they do not share the same pathogenesis.
    The American journal of surgical pathology 05/2013; · 4.06 Impact Factor
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    ABSTRACT: Glandular neoplasms involving the urinary bladder carry a challenging differential diagnosis including primary and secondary processes. We investigated the potential diagnostic utility of cadherin-17 and GATA3 in 25 primary adenocarcinomas of the urinary bladder, as compared with other commonly used markers including β-catenin and p63. Urothelial carcinoma with glandular differentiation (11), colorectal adenocarcinoma secondarily involving the bladder (25), and primary colorectal adenocarcinoma (22) were also analyzed and the results were compared using a Fisher exact test. Cadherin-17 was expressed in 23/25 primary bladder adenocarcinomas (92%), 23/25 colorectal adenocarcinomas involving the bladder (92%), 21/22 primary colorectal adenocarcinomas (95%) and entirely negative (0/11) in both components of urothelial carcinoma with glandular differentiation (P<0.001). In urothelial carcinoma with glandular differentiation, positive nuclear staining for GATA3 was evident in the urothelial component for 18% (2/11) and the glandular component for 9% (1/11) with additional tumors showing only cytoplasmic staining. Nuclear reactivity for GATA3 was not present in primary bladder adenocarcinoma and primary/secondary colorectal adenocarcinoma (P<0.05). Positive nuclear and cytoplasmic immunostaining for β-catenin was evident in 21/22 primary colorectal adenocarcinomas (95%) and 23/25 cases of secondary involvement by colorectal adenocarcinoma (92%). In contrast, positive membranous and cytoplasmic staining for β-catenin was observed in 23/25 primary bladder adenocarcinomas (92%) and 11/11 urothelial carcinomas with glandular differentiation (100%, P<0.001). p63 was expressed only in the urothelial component of urothelial carcinoma with glandular differentiation and not in the glandular component (P<0.001). In summary, cadherin-17 is a relatively specific and sensitive marker for primary adenocarcinoma of the urinary bladder, distinguishing it from urothelial carcinoma with glandular differentiation. However, it does not distinguish primary bladder adenocarcinoma from secondary involvement by colorectal adenocarcinoma. The pattern of reactivity for β-catenin remains the most useful marker for distinguishing these two tumors.Modern Pathology advance online publication, 25 January 2013; doi:10.1038/modpathol.2012.229.
    Modern Pathology 01/2013; · 5.25 Impact Factor
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    ABSTRACT: Multilocular cystic renal cell carcinoma (RCC) is an uncommon renal neoplasm composed of thin fibrous septa lining multiple cystic spaces and associated with an excellent prognosis. Clear cells with generally low-grade nuclear features line the cystic spaces and may be present within the fibrous septa, although solid mass-forming areas are by definition absent. Despite the excellent prognosis, molecular-genetic alterations are similar to those of clear cell RCC. Immunohistochemical staining characteristics, however, have not been well elucidated. We studied 24 cases of multilocular cystic RCC, classified according to the 2004 World Health Organization System. Immunohistochemical analysis was performed using an automated immunostainer for CD10, cytokeratin 7 (CK7), α-methylacyl-CoA-racemase, epithelial membrane antigen (EMA), cytokeratin CAM 5.2, carbonic anhydrase IX (CA-IX), estrogen/progesterone receptors, smooth muscle actin, PAX-2, and vimentin. Twenty-four cases of grade 1 to 2 clear cell RCC were stained for comparison. Multilocular cystic RCC and control cases of clear cell RCC showed the following results, respectively: CD10 (63%, 96%), CK7 (92%, 38%), α-methylacyl-CoA-racemase (21%, 67%), vimentin (58%, 33%), estrogen receptor (8%, 8%), CAM 5.2 (100%, 96%), EMA, CA-IX, PAX-2 (all 100%), and progesterone receptor (0%). Smooth muscle actin highlighted myofibroblastic cells within the septa of multilocular cystic RCC and the fine capillary vascular network of clear cell RCC. In summary, multilocular cystic RCC showed expression of common clear cell RCC markers CA-IX, EMA, and PAX-2, supporting the hypothesis that multilocular cystic RCC is a subtype of clear cell RCC. In contrast to clear cell RCC, tumors less frequently expressed CD10 (63% and often focal vs. 96% and diffuse) and more frequently expressed CK7 (92%), often diffusely (63%). Coexpression of CA-IX and CK7 represents a point of overlap with the recently described clear cell papillary RCC, which also may show a prominent cystic architecture. However, the latter lacks mutation of the VHL gene and deletion of chromosome 3p by molecular methodologies.
    The American journal of surgical pathology 10/2012; 36(10):1425-1433. · 4.06 Impact Factor
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    ABSTRACT: Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice. Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF) formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue. Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer.
    PLoS ONE 01/2012; 7(10):e47873. · 3.73 Impact Factor
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    ABSTRACT: Cardiac allograft vasculopathy (CAV) is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant) versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV. In a prospective cohort study, we developed multivariate regression models evaluating markers of atherothrombosis (fibrin, antithrombin and tissue plasminogen activator [tPA]) and endothelial activation (intercellular adhesion molecule-1) in serial biopsies obtained during the first three months post-transplantation from 172 patients (median follow-up = 6.3 years; min = 0.37 years, max = 16.3 years). Presence of fibrin was the dominant predictor in first-biopsy models (Odds Ratio [OR] for one- and 10-year graft failure due to CAV = 38.70, p = 0.002, 95% CI = 4.00-374.77; and 3.99, p = 0.005, 95% CI = 1.53-10.40) and loss of tPA was predominant in three-month models (OR for one- and 10-year graft failure due to CAV = 1.81, p = 0.025, 95% CI = 1.08-3.03; and 1.31, p = 0.001, 95% CI = 1.12-1.55). First-biopsy and three-month models had similar predictive and discriminative accuracy and were comparable in their capacities to correctly classify patient outcomes, with the exception of 10-year graft failure due to CAV in which the three-month model was more predictive. Both models had particularly high negative predictive values (e.g., First-biopsy vs. three-month models: 99% vs. 100% at 1-year and 96% vs. 95% at 10-years). Patients with absence of fibrin in the first biopsy and persistence of normal tPA in subsequent biopsies rarely develop CAV or graft failure during the next 10 years and potentially could be monitored less invasively. Presence of early risk markers in the transplanted heart may be secondary to ischemia/reperfusion injury, a potentially modifiable factor.
    PLoS ONE 01/2012; 7(4):e36100. · 3.73 Impact Factor
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    ABSTRACT: Lymphoepithelioma-like carcinoma (LELC) in the urinary tract is a rare malignancy, named for its resemblance to nasopharyngeal undifferentiated carcinoma or lymphoepithelioma. Investigation of immunohistochemical and molecular characteristics of bladder LELC is limited. The pathogenesis and biological behavior of these tumors are controversial. We examined clinicopathologic features of the urinary tract LELC, including light microscopy; immunohistochemistry for cytokeratin 7 (CK7), CK20, 34βE12, p53, p63, α-methylacyl-CoA racemase, thyroid transcription factor-1, Epstein-Barr virus latent membrane protein-1, and CD30; in situ hybridization for human papillomavirus; and UroVysion fluorescence in situ hybridization (FISH). We identified tumors from 34 patients, the largest series to date, (male:female, 2.8:1), ranging from 54 to 84 years of age (mean, 70 years). Urothelial carcinoma in situ was identified in 50% of patients. 34βE12 (75%), CK7 (57%), and p63 (53%) were frequently positive in tumor cells, whereas thyroid transcription factor-1 and CD30 were consistently negative. Expression of p53 was noted in a subset of tumors (61%), whereas CK20 staining was negative with weak positivity in a single case. UroVysion FISH showed frequent chromosomal abnormalities similar to those of urothelial carcinoma. In tumors with concurrent urothelial, squamous, sarcomatoid, and glandular components, identical FISH abnormalities were noted in both areas. In situ hybridization for human papillomavirus and immunostaining for Epstein-Barr virus were negative in all studied lesions. Five patients with pure or predominant LELC tumors treated with transurethral resection and followed by chemotherapy were alive without evidence of disease at 2 to 5 years. In contrast, 2 patients treated in this manner with <50% LELC morphology had death from disease or distant metastasis. Urinary tract LELC is a rare histologic variant of urothelial carcinoma. The frequent presence of UroVysion FISH abnormalities, urothelial carcinoma in situ, and p53 positivity by immunohistochemistry in cases of urinary tract LELC suggests a similar pathogenesis to high-grade invasive urothelial carcinoma. In contrast to typical urothelial carcinoma, CK20 is frequently negative in LELC. Our findings support the hypothesis that pure or predominant LELC may be treated with transurethral resection and chemotherapy. However, a large-scale study with long-term follow-up is needed to better understand the biological behavior of urinary bladder LELC.
    The American journal of surgical pathology 03/2011; 35(4):474-83. · 4.06 Impact Factor
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    ABSTRACT: To evaluate the histological and immunohistochemical characteristics of ectopic prostatic tissue. We studied 20 cases of ectopic prostate. In 85% (17/20) of the cases, the ectopic prostatic tissue was located in the bladder; in the remaining cases, it was located in the urethra. In 60% of the cases (12/20), no significant inflammatory or reactive/reparative changes were identified in the adjacent tissue. Immunohistochemical stains for prostate-specific antigen, prostate-specific acid phosphatase, and prostein were positive in the glandular epithelial cells of all cases. Stains for 34βE12 and p63 confirmed the presence of basal cells in all cases. There was no overexpression of α-methylacyl-CoA racemase in any of the cases. There was cytoplasmic luminal staining for CD10 and cytoplasmic staining for cytokeratin 18 in acinar cells in all cases. In cases in which followup data were available, no patient was found to have residual or recurrent ectopic prostatic tissue and none developed prostatic adenocarcinoma. Ectopic prostatic tissue is occasionally encountered in the lower urinary tract, most commonly in the bladder and urethra of males. Ectopic prostatic tissue has histological and immunohistochemical characteristics that are indistinguishable from those of normal prostatic tissue, and most likely represents the persistence of embryonic structures.
    Histopathology 03/2011; 58(5):750-8. · 2.86 Impact Factor
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2011; 30(4).
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2011; 30(4).
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    ABSTRACT: Medicinal mushroom Ganoderma lucidum is one of the most esteemed natural products that have been used in the traditional Chinese medicine. In this article, we demonstrate that G. lucidum triterpene extract (GLT) suppresses proliferation of human colon cancer cells HT-29 and inhibits tumor growth in a xenograft model of colon cancer. These effects of GLT are associated with the cell cycle arrest at G0/G1 and the induction of the programmed cell death Type II-autophagy in colon cancer cells. Here, we show that GLT induces formation of autophagic vacuoles and upregulates expression of Beclin-1 (1.3-fold increase) and LC-3 (7.3-fold increase) proteins in colon cancer cells and in tumors in a xenograft model (Beclin-1, 3.9-fold increase; LC-3, 1.9-fold increase). Autophagy is mediated through the inhibition of p38 mitogen-activated protein kinase (p38 MAPK) because p38 MAPK inhibitor, SB202190, induces autophagy and expression of Beclin-1 (1.2-fold increase) and LC-3 (7.4-fold increase), and GLT suppresses phosphorylation of p38 MAPK ( approximately 60% inhibition) in colon cancer cells. Taken together, our data demonstrate a novel mechanism responsible for the inhibition of colon cancer cells by G. lucidum and suggest GLT as natural product for the treatment of colon cancer.
    Nutrition and Cancer 01/2010; 62(5):630-40. · 2.70 Impact Factor
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2010; 29(2).
  • Journal of Heart and Lung Transplantation - J HEART LUNG TRANSPLANT. 01/2010; 29(2).
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    Journal of Clinical Oncology 01/2009; 27(3):460-3. · 18.04 Impact Factor
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    ABSTRACT: Sarcomatoid urothelial carcinoma of the urinary bladder is an uncommon neoplasm with biphasic morphology exhibiting both epithelial and sarcomatoid components. Whether this tumor arises from a single cancer stem cell with subsequent differentiation or represents collision of the progeny of two separate cancer stem cells is a matter of controversy. To clarify its clonal origin, we analyzed the TP53 mutation status of a series of 17 sarcomatoid urothelial carcinomas using single-strand conformation polymorphism, DNA sequencing and p53 immunohistochemistry. Sarcomatoid and epithelial tumor components were separately microdissected using laser capture microdissection. Five out of the 17 sarcomatoid urothelial carcinomas contained TP53 point mutations in exons 5 and 8. In all five cases, the TP53 point mutations were identical in both the epithelial and sarcomatoid components. The sarcomatoid and epithelial tumor components in all 17 cases showed concordant p53 expression patterns. Our results suggest that despite their conspicuous divergence at the phenotypic level, the sarcomatoid and carcinomatoid elements of this uncommon tumor share a common clonal origin.
    Modern Pathology 12/2008; 22(1):113-8. · 5.25 Impact Factor
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    ABSTRACT: Sarcomatoid carcinoma (carcinosarcoma) of the upper urinary collecting system is a rare aggressive malignancy composed of malignant epithelial and stromal components. Because of the paucity of reported cases, the clinical behavior, molecular alterations, and potential therapies for this malignancy are not well understood. Eight cases of sarcomatoid carcinoma involving the upper urinary tract were studied. Clinicopathologic characteristics were reviewed. Immunohistochemical expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)/neu, c-kit, and p53 was analyzed in each case. Evaluation for amplification of EGFR and HER2 genes was performed by interphase fluorescence in situ hybridization (FISH). Each tumor was also examined for gains of chromosomes 3, 7, and 17 and for loss of chromosome 9p21 by UroVysion FISH (Vysis, Downers Grove, IL). The patients we studied were 5 females and 3 males, ranging in age from 56 to 78 years (mean age, 69 years). Presenting symptoms included gross hematuria, flank mass, urinary obstruction, fever, or sepsis. Radical nephroureterectomy was performed on all patients. Tumor size ranged from 2 to 13 cm. Coexisting urothelial carcinoma was present in all 8 cases. Heterologous osteosarcoma was identified in 2 cases. Pathologic stage was pT4 in 5 cases and pT3 in 3 cases. Lymph node metastases were present in 5 patients at the time of surgery. Of 8 patients, 7 died within 2 years after surgery. EGFR immunostaining had moderately to strongly positive results in 6 of 8 cases. Both HER2/neu and c-kit immunostaining had negative results in all cases. p53 immunostaining had positive results in 5 of 8 cases. The EGFR polysomy was demonstrated in 7 of 8 cases. No amplification of HER2/neu was present in any case. UroVysion FISH showed abnormalities typical of urothelial carcinoma in all 8 cases. In conclusion, the prognosis of sarcomatoid carcinoma of the upper urinary tract is extremely poor, most patients died within 2 years (7/8 patients). Gains of chromosome 3, 7, and 17 and loss of chromosome 9p21 were commonly observed in these tumors. Our findings suggest that targeted therapy may be a rational strategy in the management of these patients.
    Human pathology 10/2008; 40(2):211-7. · 3.03 Impact Factor
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    ABSTRACT: Ovarian tumors frequently express c-Kit and/or platelet-derived growth factor receptors (PDGFRs). Imatinib mesylate blocks the growth of ovarian cancer cells in vitro and may enhance the activity of chemotherapy. This study was conducted to determine the activity of imatinib in combination with docetaxel in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Eligible patients had recurrent, platinum-resistant, or refractory EOC that expressed PDGFRalpha or c-kit, as determined by immunohistochemistry. Imatinib mesylate at a dose of 600 mg orally once daily was administered continuously with docetaxel at a dose of 30 mg/m(2) given intravenously once weekly in Weeks 1 through 4 of every 6-week cycle. The primary endpoint was objective response rate (ORR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Thirty-four patients were screened for PDGFRalpha and c-kit expression to enroll 23 patients between December 2003 and October 2005. Four patients had c-kit-positive/PDGFR-negative tumors, 11 patients had PDGFR-positive/c-kit-negative tumors, and 8 patients had c-kit-positive/PDGFR-positive tumors. The median patient age was 56 years (range, 33-76 years). Patients had received a median of 3 prior treatments. The ORR was 21.7% and included 1 complete and 4 partial responses. An additional 3 patients had stable disease for more than 4 months. Expression of PDGFR, c-kit, phosphatase and tensin homolog (PTEN), and phosphorylated protein kinase B (Akt) did not predict response to therapy. The most common adverse events encountered were fatigue (83%), nausea (74%), diarrhea (61%), anorexia (52%), and edema (65%), and the majority of those events were graded as grade 1 or 2. The combination imatinib and docetaxel was tolerated in patients with heavily pretreated EOC that expressed c-kit or PDGFRalpha. Few patients had sustained responses or stable disease.
    Cancer 08/2008; 113(4):723-32. · 5.20 Impact Factor

Publication Stats

806 Citations
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194.11 Total Impact Points

Institutions

  • 2013
    • University of Verona
      • Department of Pathology
      Verona, Veneto, Italy
  • 2002–2013
    • Indiana University-Purdue University Indianapolis
      • • Department of Pathology and Laboratory Medicine
      • • Department of Medicine
      Indianapolis, IN, United States
  • 2006
    • Indiana University-Purdue University School of Medicine
      • Department of Pathology and Laboratory Medicine
      Indianapolis, IN, United States