Polysomy

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Keith D. Lindor - One of the best experts on this subject based on the ideXlab platform.

  • clinical implications of serial versus isolated biliary fluorescence in situ hybridization fish Polysomy in primary sclerosing cholangitis
    Scandinavian Journal of Gastroenterology, 2017
    Co-Authors: Kevin P. Quinn, James H. Tabibian, Keith D. Lindor
    Abstract:

    AbstractBackground: Cholangiocarcinoma (CCA) is a leading cause of death in patients with primary sclerosing cholangitis (PSC). Biliary Polysomy detected by fluorescence in situ hybridization (FISH) helps to identify patients with early CCA, but not all PSC patients with Polysomy develop CCA. Here, we examined the features and clinical outcomes of PSC patients with serial versus isolated Polysomy.Methods: All patients with PSC who underwent ≥1 endoscopic retrograde cholangiography (ERC) with FISH testing at Mayo Clinic, Rochester from 2008–2011 were identified. Patients diagnosed with CCA at the time of initial Polysomy were excluded. Serial Polysomy was defined as Polysomy on ≥2 ERCs; isolated Polysomy was defined as Polysomy once followed by all nonPolysomy results. The primary outcome was the diagnosis of CCA.Results: Twenty-seven patients with Polysomy and ≥1 subsequent ERC with FISH were identified. Of these, 11 (40.7%) had serial Polysomy and 16 (59.3%) had isolated Polysomy. CCA was more likely to ...

  • Clinical implications of serial versus isolated biliary fluorescence in situ hybridization (FISH) Polysomy in primary sclerosing cholangitis
    Scandinavian journal of gastroenterology, 2016
    Co-Authors: Kevin P. Quinn, James H. Tabibian, Keith D. Lindor
    Abstract:

    Cholangiocarcinoma (CCA) is a leading cause of death in patients with primary sclerosing cholangitis (PSC). Biliary Polysomy detected by fluorescence in situ hybridization (FISH) helps to identify patients with early CCA, but not all PSC patients with Polysomy develop CCA. Here, we examined the features and clinical outcomes of PSC patients with serial versus isolated Polysomy. All patients with PSC who underwent ≥1 endoscopic retrograde cholangiography (ERC) with FISH testing at Mayo Clinic, Rochester from 2008-2011 were identified. Patients diagnosed with CCA at the time of initial Polysomy were excluded. Serial Polysomy was defined as Polysomy on ≥2 ERCs; isolated Polysomy was defined as Polysomy once followed by all nonPolysomy results. The primary outcome was the diagnosis of CCA. Twenty-seven patients with Polysomy and ≥1 subsequent ERC with FISH were identified. Of these, 11 (40.7%) had serial Polysomy and 16 (59.3%) had isolated Polysomy. CCA was more likely to be diagnosed in patients with serial versus isolated Polysomy (36.4% vs. 6.3%; p = .046). Overall, four patients (36.4%) with serial Polysomy and three (18.8%) with isolated Polysomy underwent liver transplantation (LT), with time to LT being significantly shorter for the former (14.0 vs. 65.4 months; p = .0003). Biliary Polysomy reverted in ≥50% of patients with PSC; this group appears to be at decreased risk of CCA compared to those with serial Polysomy. Nevertheless, both groups should be followed closely, and those with serial Polysomy may benefit from early LT evaluation.

  • Primary sclerosing cholangitis patients with serial Polysomy fluorescence in situ hybridization results are at increased risk of cholangiocarcinoma.
    The American journal of gastroenterology, 2011
    Co-Authors: Emily G. Barr Fritcher, Keith D. Lindor, Benjamin R. Kipp, Jesse S. Voss, Amy C. Clayton, Kevin C. Halling, Gregory J. Gores
    Abstract:

    A Polysomy fluorescence in situ hybridization (FISH) result in a pancreatobiliary brushing from a patient with primary sclerosing cholangitis (PSC) is very worrisome for carcinoma. However, treatment is not recommended unless verified by corroborative evidence of malignancy because of less than perfect test specificity in this population. The aim of this study was to evaluate the clinical outcome of PSC patients with serial Polysomy FISH results. Patients with PSC underwent endoscopic retrograde cholangiopancreatography with brushings when clinically indicated per standard practice. Brushings were evaluated by routine cytology and FISH. Retrospective review identified patients with a Polysomy FISH result without definitive imaging or pathological evidence of malignancy at the time of the first Polysomy, who underwent follow-up examinations including subsequent FISH testing (n=30). Patient records were reviewed to determine clinical outcome. In all, 9 of 13 patients (69%) with a subsequent Polysomy result (i.e., serial Polysomy) were diagnosed with cholangiocarcinoma (CCA) compared with 3 of 17 patients (18%) with subsequent non-Polysomy results (P=0.008). There was a significant difference in time to a diagnosis of CCA between PSC patients with serial Polysomy compared with those with subsequent non-Polysomy (P=0.01). In four patients with serial Polysomy results, imaging/pathological evidence of CCA was not found until 1-2.7 years after the initial Polysomy FISH result. FISH may detect polysomic cells in pancreatobiliary brushings before other pathological or imaging techniques identify CCA. Patients with serial Polysomy FISH results are at higher risk for having CCA than those with subsequent non-Polysomy FISH results.

  • long term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis
    Hepatology, 2010
    Co-Authors: Sanjay Bangarulingam, Emily G. Barr Fritcher, Kevin C. Halling, Gregory J. Gores, Einar Bjornsson, Felicity Enders, Keith D. Lindor
    Abstract:

    Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) is a cytological test designed to enhance early CCA diagnosis. The long-term outcome of PSC patients with a positive FISH test (Polysomy, trisomy/tetrasomy) are unclear. All PSC patients with at least one FISH test were identified and defined to have CCA if they had a positive tissue biopsy, positive cytology, or evidence of cancer in the explant after liver transplantation. A total of 235 PSC patients had at least one FISH test performed, and 56 patients had CCA on histopathology (n = 35) or cytology (n = 21). Overall, 120 of 235 (51%) of PSC patients tested for FISH were positive, but only one third of these positive patients had CCA. Sensitivity and specificity for FISH Polysomy were 46% and 88%, and for trisomy/tetrasomy they were 25% and 67%, respectively. Survival analysis showed that patients with FISH Polysomy had an outcome similar to patients with CCA; whereas FISH trisomy/tetrasomy patients had an outcome similar to patients with negative FISH tests. The FISH Polysomy patients without cancer compared with those with CCA had lower serum bilirubin, lower carbohydrate antigen 19-9 (CA 19-9), lower Mayo risk score, and lower occurrence of dominant strictures. Conclusion: In PSC patients, the presence of a dominant stricture plus FISH Polysomy has a specificity of 88% for CCA. Patients with FISH showing trisomy or tetrasomy have a similar outcome to patients with negative FISH. FISH testing should be used selectively in patients with other signs indicating CCA and not as a screening tool in all PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). (HEPATOLOGY 2009.)

Jan F. Silverman - One of the best experts on this subject based on the ideXlab platform.

  • Correlation of immunohistochemical expression of p53 with unamplified chromosome 17 Polysomy in invasive breast carcinoma
    Applied immunohistochemistry & molecular morphology : AIMM, 2011
    Co-Authors: Uma Krishnamurti, Folefac D Atem, Alireza Zarineh, Jan F. Silverman
    Abstract:

    p53 functions as a tumor suppressor gene and is frequently mutated and inactivated in several human cancers. Some studies have shown p53 overexpression in breast cancer to be an independent prognostic indicator. A subset of breast cancers have chromosome 17 Polysomy. Although p53 immunostaining has been found to correlate with chromosome 17 Polysomy in nonsmall cell lung carcinomas, head and neck squamous cell carcinomas, and bladder carcinomas, its expression has not been correlated with chromosome 17 Polysomy in breast carcinomas. In this study, we compared p53 expression by immunohistochemistry in cases of invasive breast carcinoma showing unamplified chromosome 17 Polysomy (P) with cases showing HER2 amplification (A) and with those showing neither amplification nor Polysomy (N). There was a significant overexpression of p53 in both cases with HER2 amplification and unamplified Polysomy 17 compared with cases with neither amplification nor Polysomy (7% of N, 25% of P, and 37% of A group were p53 positive). We have shown in an earlier study that invasive breast carcinoma with unamplified chromosome 17 Polysomy is associated with several adverse prognostic indicators including a higher Nottingham score and greater estrogen receptor (ER) negativity with a trend toward the amplified group, in contrast to patients with neither amplification nor Polysomy. In this study, we now show that p53 positivity in unamplified 17 Polysomy identifies cases that are associated with an even higher Nottingham score and greater hormone receptor negativity that is similar to cases with HER2 amplification.

  • poor prognostic significance of unamplified chromosome 17 Polysomy in invasive breast carcinoma
    Modern Pathology, 2009
    Co-Authors: Uma Krishnamurti, Jennifer L Hammers, Patrick Storto, Jan F. Silverman, Folefac D Atem
    Abstract:

    The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 20% of breast cancers, with HER2 gene amplification responsible for protein overexpression in the vast majority of patients. A subset of breast cancers have chromosome 17 aneusomy, due to either 17 monosomy (a single copy of chromosome 17) or Polysomy (increased copy numbers of chromosome 17). Although HER2 overexpression is an established adverse prognostic factor in breast cancer, the role of unamplified chromosome 17 Polysomy is uncertain and there is a paucity of literature on the correlation of chromosome 17 aneusomy with important prognostic and predictive pathologic factors in invasive breast carcinoma. Furthermore, while patients showing HER2 amplification with or without Polysomy 17 are treated with trastuzumab with or without other chemotherapy, treatment of patients with unamplified chromosome 17 Polysomy is not well defined. Currently most of these patients are treated similar to patients with neither amplification nor 17 Polysomy. The aim of this study was to compare some prognostic and predictive factors in invasive breast carcinoma in patients with unamplified chromosome 17 Polysomy with that seen in cases with HER2 gene amplification and those with neither amplification or Polysomy. We found that invasive breast carcinomas with unamplified chromosome 17 Polysomy are associated with several adverse prognostic indicators such as a higher nuclear grade, mitotic activity, Nottingham score, histologic grade, tumor stage, and greater estrogen receptor negativity with a trend towards the amplified group, in contrast to patients with neither amplification or Polysomy. Although most patients with unamplified 17 Polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+ positive score. An increased adverse role for unamplified Polysomy along with 3+ protein expression in some patients supports the idea that these patients should be considered for therapy with trastuzumab and/or anthracyclines.

  • Poor prognostic significance of unamplified chromosome 17 Polysomy in invasive breast carcinoma.
    Modern Pathology, 2009
    Co-Authors: Uma Krishnamurti, Jennifer L Hammers, Patrick Storto, Folefac D Atem, Jan F. Silverman
    Abstract:

    Poor prognostic significance of unamplified chromosome 17 Polysomy in invasive breast carcinoma

James H. Tabibian - One of the best experts on this subject based on the ideXlab platform.

  • clinical implications of serial versus isolated biliary fluorescence in situ hybridization fish Polysomy in primary sclerosing cholangitis
    Scandinavian Journal of Gastroenterology, 2017
    Co-Authors: Kevin P. Quinn, James H. Tabibian, Keith D. Lindor
    Abstract:

    AbstractBackground: Cholangiocarcinoma (CCA) is a leading cause of death in patients with primary sclerosing cholangitis (PSC). Biliary Polysomy detected by fluorescence in situ hybridization (FISH) helps to identify patients with early CCA, but not all PSC patients with Polysomy develop CCA. Here, we examined the features and clinical outcomes of PSC patients with serial versus isolated Polysomy.Methods: All patients with PSC who underwent ≥1 endoscopic retrograde cholangiography (ERC) with FISH testing at Mayo Clinic, Rochester from 2008–2011 were identified. Patients diagnosed with CCA at the time of initial Polysomy were excluded. Serial Polysomy was defined as Polysomy on ≥2 ERCs; isolated Polysomy was defined as Polysomy once followed by all nonPolysomy results. The primary outcome was the diagnosis of CCA.Results: Twenty-seven patients with Polysomy and ≥1 subsequent ERC with FISH were identified. Of these, 11 (40.7%) had serial Polysomy and 16 (59.3%) had isolated Polysomy. CCA was more likely to ...

  • Clinical implications of serial versus isolated biliary fluorescence in situ hybridization (FISH) Polysomy in primary sclerosing cholangitis
    Scandinavian journal of gastroenterology, 2016
    Co-Authors: Kevin P. Quinn, James H. Tabibian, Keith D. Lindor
    Abstract:

    Cholangiocarcinoma (CCA) is a leading cause of death in patients with primary sclerosing cholangitis (PSC). Biliary Polysomy detected by fluorescence in situ hybridization (FISH) helps to identify patients with early CCA, but not all PSC patients with Polysomy develop CCA. Here, we examined the features and clinical outcomes of PSC patients with serial versus isolated Polysomy. All patients with PSC who underwent ≥1 endoscopic retrograde cholangiography (ERC) with FISH testing at Mayo Clinic, Rochester from 2008-2011 were identified. Patients diagnosed with CCA at the time of initial Polysomy were excluded. Serial Polysomy was defined as Polysomy on ≥2 ERCs; isolated Polysomy was defined as Polysomy once followed by all nonPolysomy results. The primary outcome was the diagnosis of CCA. Twenty-seven patients with Polysomy and ≥1 subsequent ERC with FISH were identified. Of these, 11 (40.7%) had serial Polysomy and 16 (59.3%) had isolated Polysomy. CCA was more likely to be diagnosed in patients with serial versus isolated Polysomy (36.4% vs. 6.3%; p = .046). Overall, four patients (36.4%) with serial Polysomy and three (18.8%) with isolated Polysomy underwent liver transplantation (LT), with time to LT being significantly shorter for the former (14.0 vs. 65.4 months; p = .0003). Biliary Polysomy reverted in ≥50% of patients with PSC; this group appears to be at decreased risk of CCA compared to those with serial Polysomy. Nevertheless, both groups should be followed closely, and those with serial Polysomy may benefit from early LT evaluation.

  • biliary multifocal chromosomal Polysomy and cholangiocarcinoma in primary sclerosing cholangitis
    The American Journal of Gastroenterology, 2015
    Co-Authors: John E. Eaton, James H. Tabibian, Emily G. Barr Fritcher, Benjamin R. Kipp, Kevin C. Halling, Gregory J. Gores, Elizabeth J. Atkinson, Mark Topazian, Andrea A. Gossard, Konstantinos N. Lazaridis
    Abstract:

    Biliary Multifocal Chromosomal Polysomy and Cholangiocarcinoma in Primary Sclerosing Cholangitis

  • Biliary multifocal chromosomal Polysomy and cholangiocarcinoma in primary sclerosing cholangitis.
    The American journal of gastroenterology, 2015
    Co-Authors: John E. Eaton, James H. Tabibian, Emily G. Barr Fritcher, Benjamin R. Kipp, Kevin C. Halling, Gregory J. Gores, Elizabeth J. Atkinson, Mark Topazian, Andrea A. Gossard, Konstantinos N. Lazaridis
    Abstract:

    Polysomy detected by fluorescence in situ hybridization (FISH) is associated with cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC). However, a subset of PSC patients with Polysomy do not manifest CCA even after long-term follow-up. It is unknown if patients with chromosomal gains detected by FISH in multiple areas of the biliary tree (i.e., multifocal Polysomy, MFP) are more likely to be diagnosed with CCA than patients with unifocal Polysomy (UFP). Therefore, our aim is to determine whether patients with MFP are more likely to manifest CCA compared with patients with other chromosomal abnormalities including UFP and other FISH subtypes. We performed a retrospective review of PSC patients without a mass lesion who underwent FISH testing at our institution from 1 January 2005 to 1 July 2013. Three-hundred and seventy-one PSC patients were included. Compared with patients with UFP, those with MFP were more likely to have weight loss (32 vs. 9%), suspicious cytology (45 vs. 13%) and develop serial Polysomy (91 vs. 35%). MFP was associated with CCA (hazard ratio (HR), 82.42; 95% confidence interval (CI), 24.50-277.31) and was the strongest predictor of cancer diagnosis. Suspicious cytology (HR, 26.31; 95% CI, 8.63-80.24) and UFP (HR, 13.27; 95% CI, 3.32-53.08) were also predictive of CCA. MFP, UFP and suspicious cytology remained associated with CCA in the multivariable model. Compared with other FISH subtypes, MFP is the strongest predictor of CCA. However, patients with UFP and suspicious cytology (regardless of FISH status) are also at an increased risk for CCA.

Kevin P. Quinn - One of the best experts on this subject based on the ideXlab platform.

  • clinical implications of serial versus isolated biliary fluorescence in situ hybridization fish Polysomy in primary sclerosing cholangitis
    Scandinavian Journal of Gastroenterology, 2017
    Co-Authors: Kevin P. Quinn, James H. Tabibian, Keith D. Lindor
    Abstract:

    AbstractBackground: Cholangiocarcinoma (CCA) is a leading cause of death in patients with primary sclerosing cholangitis (PSC). Biliary Polysomy detected by fluorescence in situ hybridization (FISH) helps to identify patients with early CCA, but not all PSC patients with Polysomy develop CCA. Here, we examined the features and clinical outcomes of PSC patients with serial versus isolated Polysomy.Methods: All patients with PSC who underwent ≥1 endoscopic retrograde cholangiography (ERC) with FISH testing at Mayo Clinic, Rochester from 2008–2011 were identified. Patients diagnosed with CCA at the time of initial Polysomy were excluded. Serial Polysomy was defined as Polysomy on ≥2 ERCs; isolated Polysomy was defined as Polysomy once followed by all nonPolysomy results. The primary outcome was the diagnosis of CCA.Results: Twenty-seven patients with Polysomy and ≥1 subsequent ERC with FISH were identified. Of these, 11 (40.7%) had serial Polysomy and 16 (59.3%) had isolated Polysomy. CCA was more likely to ...

  • Clinical implications of serial versus isolated biliary fluorescence in situ hybridization (FISH) Polysomy in primary sclerosing cholangitis
    Scandinavian journal of gastroenterology, 2016
    Co-Authors: Kevin P. Quinn, James H. Tabibian, Keith D. Lindor
    Abstract:

    Cholangiocarcinoma (CCA) is a leading cause of death in patients with primary sclerosing cholangitis (PSC). Biliary Polysomy detected by fluorescence in situ hybridization (FISH) helps to identify patients with early CCA, but not all PSC patients with Polysomy develop CCA. Here, we examined the features and clinical outcomes of PSC patients with serial versus isolated Polysomy. All patients with PSC who underwent ≥1 endoscopic retrograde cholangiography (ERC) with FISH testing at Mayo Clinic, Rochester from 2008-2011 were identified. Patients diagnosed with CCA at the time of initial Polysomy were excluded. Serial Polysomy was defined as Polysomy on ≥2 ERCs; isolated Polysomy was defined as Polysomy once followed by all nonPolysomy results. The primary outcome was the diagnosis of CCA. Twenty-seven patients with Polysomy and ≥1 subsequent ERC with FISH were identified. Of these, 11 (40.7%) had serial Polysomy and 16 (59.3%) had isolated Polysomy. CCA was more likely to be diagnosed in patients with serial versus isolated Polysomy (36.4% vs. 6.3%; p = .046). Overall, four patients (36.4%) with serial Polysomy and three (18.8%) with isolated Polysomy underwent liver transplantation (LT), with time to LT being significantly shorter for the former (14.0 vs. 65.4 months; p = .0003). Biliary Polysomy reverted in ≥50% of patients with PSC; this group appears to be at decreased risk of CCA compared to those with serial Polysomy. Nevertheless, both groups should be followed closely, and those with serial Polysomy may benefit from early LT evaluation.

Uma Krishnamurti - One of the best experts on this subject based on the ideXlab platform.

  • Correlation of immunohistochemical expression of p53 with unamplified chromosome 17 Polysomy in invasive breast carcinoma
    Applied immunohistochemistry & molecular morphology : AIMM, 2011
    Co-Authors: Uma Krishnamurti, Folefac D Atem, Alireza Zarineh, Jan F. Silverman
    Abstract:

    p53 functions as a tumor suppressor gene and is frequently mutated and inactivated in several human cancers. Some studies have shown p53 overexpression in breast cancer to be an independent prognostic indicator. A subset of breast cancers have chromosome 17 Polysomy. Although p53 immunostaining has been found to correlate with chromosome 17 Polysomy in nonsmall cell lung carcinomas, head and neck squamous cell carcinomas, and bladder carcinomas, its expression has not been correlated with chromosome 17 Polysomy in breast carcinomas. In this study, we compared p53 expression by immunohistochemistry in cases of invasive breast carcinoma showing unamplified chromosome 17 Polysomy (P) with cases showing HER2 amplification (A) and with those showing neither amplification nor Polysomy (N). There was a significant overexpression of p53 in both cases with HER2 amplification and unamplified Polysomy 17 compared with cases with neither amplification nor Polysomy (7% of N, 25% of P, and 37% of A group were p53 positive). We have shown in an earlier study that invasive breast carcinoma with unamplified chromosome 17 Polysomy is associated with several adverse prognostic indicators including a higher Nottingham score and greater estrogen receptor (ER) negativity with a trend toward the amplified group, in contrast to patients with neither amplification nor Polysomy. In this study, we now show that p53 positivity in unamplified 17 Polysomy identifies cases that are associated with an even higher Nottingham score and greater hormone receptor negativity that is similar to cases with HER2 amplification.

  • poor prognostic significance of unamplified chromosome 17 Polysomy in invasive breast carcinoma
    Modern Pathology, 2009
    Co-Authors: Uma Krishnamurti, Jennifer L Hammers, Patrick Storto, Jan F. Silverman, Folefac D Atem
    Abstract:

    The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 20% of breast cancers, with HER2 gene amplification responsible for protein overexpression in the vast majority of patients. A subset of breast cancers have chromosome 17 aneusomy, due to either 17 monosomy (a single copy of chromosome 17) or Polysomy (increased copy numbers of chromosome 17). Although HER2 overexpression is an established adverse prognostic factor in breast cancer, the role of unamplified chromosome 17 Polysomy is uncertain and there is a paucity of literature on the correlation of chromosome 17 aneusomy with important prognostic and predictive pathologic factors in invasive breast carcinoma. Furthermore, while patients showing HER2 amplification with or without Polysomy 17 are treated with trastuzumab with or without other chemotherapy, treatment of patients with unamplified chromosome 17 Polysomy is not well defined. Currently most of these patients are treated similar to patients with neither amplification nor 17 Polysomy. The aim of this study was to compare some prognostic and predictive factors in invasive breast carcinoma in patients with unamplified chromosome 17 Polysomy with that seen in cases with HER2 gene amplification and those with neither amplification or Polysomy. We found that invasive breast carcinomas with unamplified chromosome 17 Polysomy are associated with several adverse prognostic indicators such as a higher nuclear grade, mitotic activity, Nottingham score, histologic grade, tumor stage, and greater estrogen receptor negativity with a trend towards the amplified group, in contrast to patients with neither amplification or Polysomy. Although most patients with unamplified 17 Polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+ positive score. An increased adverse role for unamplified Polysomy along with 3+ protein expression in some patients supports the idea that these patients should be considered for therapy with trastuzumab and/or anthracyclines.

  • Poor prognostic significance of unamplified chromosome 17 Polysomy in invasive breast carcinoma.
    Modern Pathology, 2009
    Co-Authors: Uma Krishnamurti, Jennifer L Hammers, Patrick Storto, Folefac D Atem, Jan F. Silverman
    Abstract:

    Poor prognostic significance of unamplified chromosome 17 Polysomy in invasive breast carcinoma