Browsing by Author "Wang, Lisha"

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    Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation
    (Impact Journals, 2016-07-08) Caliò, Anna; Eble, John N.; Hes, Ondrej; Martignoni, Guido; Harari, Saul E.; Williamson, Sean R.; Brunelli, Matteo; Osunkoya, Adeboye O.; Wang, Lisha; Comperat, Eva; Lopez-Beltran, Antonio; Wang, Mingsheng; Zhang, Shaobo; Curless, Kendra L.; Post, Kristin M.; Chang, Hsim-Yee; Luchini, Claudio; Baldrige, Lee Ann; MacLennan, Gregory T.; Montironi, Rodolfo; Grignon, David J.; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
    BRAF mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of BRAF-mutated metanephric adenoma and to correlate BRAF mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of BRAF mutation (BRAF V600E/V600E complex, BRAF V600D, BRAF V600K and BRAF V600R) using the BRAF RGQ PCR kit (Qiagen). Immunohistochemistry was performed using monoclonal mouse antibodies against p16INK4 and VE1 (Spring Bioscience), recognizing the BRAF V600E mutant protein. Forty-one of 48 cases (85%) showed BRAF V600E mutation; none of the other BRAF variants was detected. Of 41 BRAF-mutated metanephric adenomas, 33 showed positive VE1 immunostaining (sensitivity 80%, specificity 100%); in all cases we detected p16INK4 expression regardless of BRAF mutation status. All epithelial-predominant nephroblastomas were BRAF-wild-type and none expressed VE1. The following features were associated with BRAF V600E mutation: older patients (p=0.01), female predominance (p=0.005) and the presence of a predominantly acinar architecture (p=0.003). In summary, BRAF-mutated metanephric adenomas were associated with older age, female predominance, and the presence of a predominant acinar component. A subset (20%) of BRAF-mutated metanephric adenomas was not detected by VE1 immunostaining.
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    Fluorescence in situ Hybridization in Surgical Pathology: Principles and Applications
    (Wiley, 2017) Cheng, Liang; Zhang, Shaobo; Wang, Lisha; MacLennan, Gregory T.; Davidson, Darrell D.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Identification of recurrent tumour-specific chromosomal translocations and novel fusion oncogenes has important diagnostic, therapeutic and prognostic implications. Over the past decade, fluorescence in situ hybridization (FISH) analysis of tumour samples has been one of the most rapidly growing areas in genomic medicine and surgical pathology practice. Unlike traditional cytogenetics, FISH affords a rapid analysis of formalin-fixed, paraffin-embedded cells within a routine pathology practice workflow. As more diagnostic and treatment decisions are based on results of FISH, demand for the technology will become more widespread. Common FISH-detected alterations are chromosome deletions, gains, translocations, amplifications and polysomy. These chromosome alterations may have diagnostic and therapeutic implications for many tumour types. Integrating genomic testing into cancer treatment decisions poses many technical challenges, but rapid progress is being made to overcome these challenges in precision medicine. FISH assessment of chromosomal changes relevant to differential diagnosis and cancer treatment decisions has become an important tool for the surgical pathologist. The aim of this review is to provide a theoretical and practical survey of FISH detected translocations with a focus on strategies for clinical application in surgical pathology practice.
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    Human papillomavirus (HPV)-induced neoplasia in the urinary bladder: a missing link?
    (2016) Alexander, Riley E.; Wang, Lisha; Lopez-Beltran, Antonio; Emerson, Robert E.; Montironi, Rodolfo; Pedrosa, Jose A.; Kaimakliotis, Hristos Z.; Koch, Michael O.; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of Medicine
    The discovery that the role human papillomavirus (HPV) plays in the induction of human cancer represents an important achievement in oncologic research. It has taken on even greater importance since the development of vaccines, which promise the hope of preventing these cancers from ever occurring. Because of these important implications, many have attempted to determine a possible role for the virus in cancers of the urinary bladder-an organ in close anatomic proximity to the primary sites of HPV-induced neoplasia and one which already has an established oncogenic infectious agent in Schistosoma haematobium. Here we review the current literature exploring this possible role in the most common subtype of cancer of the urinary bladder, urothelial carcinoma, and two much more rare histologic subtypes that have well established roles for HPV-induced neoplasia in other anatomic sites-squamous cell carcinoma and adenocarcinoma.
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    Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced stage colorectal cancer
    (Elsevier, 2017) Wang, Lisha; Liu, Zebing; Fisher, Kurt W.; Ren, Fei; Lv, Jiaojie; Davidson, Darrell D.; Baldridge, Lee A.; Du, Xiang; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of Medicine
    Current prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P = .001) and higher Ki-67 labeling index (LI) (P = .031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P = .031), positive p53 expression (P = .031), and negative PD-L1 expression (P = .003). The five-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P < .001). In univariate analysis, negative p53 (P = .001), low Ki-67 LI (P = .006), low PD-L1 expression (P = .044), low TNM stage (P < .001), recto-sigmoid location (P = .026), and small size (P = .013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34–4.59, P = .004), high Ki-67 LI (HR: 2.62; 95% CI: 1.12–6.14, P = .027) and high TNM stage (HR: 2.598, 95% CI: 1.55–4.37, P < .001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score ≥ 35 and Ki-67 LI ≥ 20% identifies patients with poor clinical outcome.
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    Solitary fibrous tumour of the genitourinary tract: a clinicopathological study of 11 cases and their association with the NAB2-STAT6 fusion gene
    (BMJ, 2017) Kouba, Erik; Simper, Novae B.; Chen, Shaoxiong; Williamson, Sean R.; Grignon, David J.; Eble, John N.; MacLennan, Gregory T.; Montironi, Rodolfo; Lopez-Beltran, Antonio; Osunkoya, Adeboye O.; Zhang, Shaobo; Wang, Mingsheng; Wang, Lisha; Tran, Thu; Emerson, Robert E.; Baldridge, Lee Ann; Monn, M. Francesca; Linos, Konstantinos; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of Medicine
    Aims To characterise clinicopathological features and clinical outcomes of the genitourinary tract solitary fibrous tumours, incorporating NAB2-STAT6 gene fusion status. Methods The presence of the molecular hallmark NAB2-STAT6 gene fusion and for the defining fusion partner product STAT6 was assessed in 11 cases of the genitourinary tract solitary fibrous tumours. NAB2-STAT6 gene fusion analysis was performed using a break-apart fluorescence in situ hybridisation (FISH) probe using a probe cocktail with Bacterial artificial chromosome (BAC) clones for STAT6 and NAB2. Results Eleven solitary fibrous tumours were diagnosed in eight male patients and three female patients with a mean age of 46 years (range: 11–64 years). Four of the tumours had malignant histological features, and three were considered moderate risk for metastasis. With a mean follow-up time of 61 months, 1 recurred locally and 2 presented at distant metastatic sites. Using a break-apart FISH probe cocktail, we found the NAB2-STAT6 gene fusion and nuclear STAT6 expression in 58% and 91% of cases, respectively. However, the NAB2-STAT6 fusion status was not correlated with STAT6 expression or useful in discriminating between malignant histological features or subsequent clinical outcomes in the genitourinary solitary fibrous tumours. Conclusions A subset of solitary fibrous tumours of the genitourinary tract behaved aggressively. Using a break-apart FISH probe cocktail, we found the NAB2-STAT6 gene fusion in 64% of cases. However, the NAB2-STAT6 fusion status was not correlated with STAT6 expression or useful in discriminating between low-risk or high-risk tumours and subsequent clinical outcomes.
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    TMPRSS2-ERG gene fusion is rare compared to PTEN deletions in stage T1a prostate cancer
    (Wiley, 2016-03) Fisher, Kurt W.; Zhang, Shaobo; Wang, Mingsheng; Montironi, Rodolfo; Wang, Lisha; Baldridge, Lee Ann; Wang, Jonas Y.; MacLennan, Gregory T.; Williamson, Sean R.; Lopez-Beltran, Antonio; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of Medicine
    T1a prostate cancers (cancer found incidentally in transurethral resection, <5% of the tissue) are indolent tumors of the transition zone. The overexpression of ERG and the inactivation of PTEN have been shown to be important drivers of carcinogenesis in large series of prostate cancer, but the genetics of transition zone tumors have not been well characterized. We evaluated the status of ERG and PTEN in formalin-fixed paraffin-embedded tissue using immunohistochemical and FISH analysis in 54 T1a transition zone tumors. The protein expression of ERG was determined using a rabbit monoclonal antibody and nuclear staining was scored as positive or negative. The genomic status of ERG was determined using three colored FISH using an ERG-TMPRSS2 tri-color probe set. The protein expression of PTEN was determined using a rabbit monoclonal antibody and cytoplasmic, and nuclear staining was scored as positive or negative. The genomic status of PTEN was determined using dual color FISH with a PTEN probe and a CEP10 probe. We found ERG rearrangement in 2 of 54 tumors (4%), one with protein overexpression by immunohistochemistry. PTEN inactivation was seen in 13 of 54 tumors (24%). Nine of the 13 PTEN alleles were inactivated by hemizygous deletion. No homozygous PTEN deletion was observed. PTEN deletion and ERG rearrangement were mutually exclusive. ERG rearrangement was rare compared to peripheral zone tumors and to PTEN inactivation in T1a transition zone tumors.