DNA Methylation profiles as predictors of recurrence in non muscle invasive bladder cancer: An MS-MLPA approach

Valentina Casadio, Chiara Molinari, Daniele Calistri, Michela Tebaldi, Roberta Gunelli, Luigi Serra, Fabio Falcini, Chiara Zingaretti, Rosella Silvestrini, Dino Amadori, Wainer Zoli

Research output: Contribution to journalArticle

Abstract

Background: Although non muscle invasive bladder cancer (NMIBC) generally has a good long-term prognosis, up to 80% of patients will nevertheless experience local recurrence after the primary tumor resection. The search for markers capable of accurately identifying patients at high risk of recurrence is ongoing. We retrospectively evaluated the methylation status of a panel of 24 tumor suppressor genes (TIMP3, APC, CDKN2A, MLH1, ATM, RARB, CDKN2B, HIC1, CHFR, BRCA1, CASP8, CDKN1B, PTEN, BRCA2, CD44, RASSF1, DAPK1, FHIT, VHL, ESR1, TP73, IGSF4, GSTP1 and CDH13) in primary lesions to obtain information about their role in predicting local recurrence in NMIBC. Methods. Formaldehyde-fixed paraffin-embedded (FFPE) samples from 74 patients operated on for bladder cancer were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA): 36 patients had relapsed and 38 were disease-free at the 5-year follow up. Methylation status was considered as a dichotomous variable and genes showing methylation ≥20% were defined as "positive". Results: Methylation frequencies were higher in non recurring than recurring tumors. A statistically significant difference was observed for HIC1 (P = 0.03), GSTP1 (P = 0.02) and RASSF1 (P = 0.03). The combination of the three genes showed 78% sensitivity and 66% specificity in identifying recurrent patients, with an overall accuracy of 72%. Conclusions: Our preliminary data suggest a potential role of HIC1, GSTP1 and RASSF1 in predicting local recurrence in NMIBC. Such information could help clinicians to identify patients at high risk of recurrence who require close monitoring during follow up.

Original languageEnglish
Article number94
JournalJournal of Experimental and Clinical Cancer Research
Volume32
Issue number1
DOIs
Publication statusPublished - Nov 19 2013

Fingerprint

Multiplex Polymerase Chain Reaction
DNA Methylation
Urinary Bladder Neoplasms
Methylation
Recurrence
Muscles
Tumor Suppressor Genes
Paraffin
Formaldehyde
Genes
Neoplasms
Sensitivity and Specificity

Keywords

  • Gene methylation profile
  • Non muscle invasive bladder cancer (NMIBC)
  • Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

DNA Methylation profiles as predictors of recurrence in non muscle invasive bladder cancer : An MS-MLPA approach. / Casadio, Valentina; Molinari, Chiara; Calistri, Daniele; Tebaldi, Michela; Gunelli, Roberta; Serra, Luigi; Falcini, Fabio; Zingaretti, Chiara; Silvestrini, Rosella; Amadori, Dino; Zoli, Wainer.

In: Journal of Experimental and Clinical Cancer Research, Vol. 32, No. 1, 94, 19.11.2013.

Research output: Contribution to journalArticle

Casadio, Valentina ; Molinari, Chiara ; Calistri, Daniele ; Tebaldi, Michela ; Gunelli, Roberta ; Serra, Luigi ; Falcini, Fabio ; Zingaretti, Chiara ; Silvestrini, Rosella ; Amadori, Dino ; Zoli, Wainer. / DNA Methylation profiles as predictors of recurrence in non muscle invasive bladder cancer : An MS-MLPA approach. In: Journal of Experimental and Clinical Cancer Research. 2013 ; Vol. 32, No. 1.
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abstract = "Background: Although non muscle invasive bladder cancer (NMIBC) generally has a good long-term prognosis, up to 80{\%} of patients will nevertheless experience local recurrence after the primary tumor resection. The search for markers capable of accurately identifying patients at high risk of recurrence is ongoing. We retrospectively evaluated the methylation status of a panel of 24 tumor suppressor genes (TIMP3, APC, CDKN2A, MLH1, ATM, RARB, CDKN2B, HIC1, CHFR, BRCA1, CASP8, CDKN1B, PTEN, BRCA2, CD44, RASSF1, DAPK1, FHIT, VHL, ESR1, TP73, IGSF4, GSTP1 and CDH13) in primary lesions to obtain information about their role in predicting local recurrence in NMIBC. Methods. Formaldehyde-fixed paraffin-embedded (FFPE) samples from 74 patients operated on for bladder cancer were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA): 36 patients had relapsed and 38 were disease-free at the 5-year follow up. Methylation status was considered as a dichotomous variable and genes showing methylation ≥20{\%} were defined as {"}positive{"}. Results: Methylation frequencies were higher in non recurring than recurring tumors. A statistically significant difference was observed for HIC1 (P = 0.03), GSTP1 (P = 0.02) and RASSF1 (P = 0.03). The combination of the three genes showed 78{\%} sensitivity and 66{\%} specificity in identifying recurrent patients, with an overall accuracy of 72{\%}. Conclusions: Our preliminary data suggest a potential role of HIC1, GSTP1 and RASSF1 in predicting local recurrence in NMIBC. Such information could help clinicians to identify patients at high risk of recurrence who require close monitoring during follow up.",
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T1 - DNA Methylation profiles as predictors of recurrence in non muscle invasive bladder cancer

T2 - An MS-MLPA approach

AU - Casadio, Valentina

AU - Molinari, Chiara

AU - Calistri, Daniele

AU - Tebaldi, Michela

AU - Gunelli, Roberta

AU - Serra, Luigi

AU - Falcini, Fabio

AU - Zingaretti, Chiara

AU - Silvestrini, Rosella

AU - Amadori, Dino

AU - Zoli, Wainer

PY - 2013/11/19

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AB - Background: Although non muscle invasive bladder cancer (NMIBC) generally has a good long-term prognosis, up to 80% of patients will nevertheless experience local recurrence after the primary tumor resection. The search for markers capable of accurately identifying patients at high risk of recurrence is ongoing. We retrospectively evaluated the methylation status of a panel of 24 tumor suppressor genes (TIMP3, APC, CDKN2A, MLH1, ATM, RARB, CDKN2B, HIC1, CHFR, BRCA1, CASP8, CDKN1B, PTEN, BRCA2, CD44, RASSF1, DAPK1, FHIT, VHL, ESR1, TP73, IGSF4, GSTP1 and CDH13) in primary lesions to obtain information about their role in predicting local recurrence in NMIBC. Methods. Formaldehyde-fixed paraffin-embedded (FFPE) samples from 74 patients operated on for bladder cancer were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA): 36 patients had relapsed and 38 were disease-free at the 5-year follow up. Methylation status was considered as a dichotomous variable and genes showing methylation ≥20% were defined as "positive". Results: Methylation frequencies were higher in non recurring than recurring tumors. A statistically significant difference was observed for HIC1 (P = 0.03), GSTP1 (P = 0.02) and RASSF1 (P = 0.03). The combination of the three genes showed 78% sensitivity and 66% specificity in identifying recurrent patients, with an overall accuracy of 72%. Conclusions: Our preliminary data suggest a potential role of HIC1, GSTP1 and RASSF1 in predicting local recurrence in NMIBC. Such information could help clinicians to identify patients at high risk of recurrence who require close monitoring during follow up.

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KW - Non muscle invasive bladder cancer (NMIBC)

KW - Recurrence

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