Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4

Michele Masetti, Giorgia Acquaviva, Michela Visani, Giovanni Tallini, Adele Fornelli, Moira Ragazzi, Francesco Vasuri, Daniela Grifoni, Simone Di Giacomo, Sirio Fiorino, Raffaele Lombardi, David Tuminati, Matteo Ravaioli, Carlo Fabbri, Maria Letizia Bacchi-Reggiani, Annalisa Pession, Elio Jovine, Dario de Biase

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Abstract

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection.

OBJECTIVE: The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery.

METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated.

RESULTS: Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation.

CONCLUSIONS: Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

Original languageEnglish
Pages (from-to)323-334
Number of pages12
JournalCancer Biomarkers
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 6 2018

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Survivors
Adenocarcinoma
Neoplasms
Methylation
Survival
Mutation
Immunohistochemistry
Genes

Keywords

  • Journal Article

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Masetti, M., Acquaviva, G., Visani, M., Tallini, G., Fornelli, A., Ragazzi, M., ... de Biase, D. (2018). Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4. Cancer Biomarkers, 21(2), 323-334. https://doi.org/10.3233/CBM-170464

Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4. / Masetti, Michele; Acquaviva, Giorgia; Visani, Michela; Tallini, Giovanni; Fornelli, Adele; Ragazzi, Moira; Vasuri, Francesco; Grifoni, Daniela; Di Giacomo, Simone; Fiorino, Sirio; Lombardi, Raffaele; Tuminati, David; Ravaioli, Matteo; Fabbri, Carlo; Bacchi-Reggiani, Maria Letizia; Pession, Annalisa; Jovine, Elio; de Biase, Dario.

In: Cancer Biomarkers, Vol. 21, No. 2, 06.02.2018, p. 323-334.

Research output: Contribution to journalArticle

Masetti, M, Acquaviva, G, Visani, M, Tallini, G, Fornelli, A, Ragazzi, M, Vasuri, F, Grifoni, D, Di Giacomo, S, Fiorino, S, Lombardi, R, Tuminati, D, Ravaioli, M, Fabbri, C, Bacchi-Reggiani, ML, Pession, A, Jovine, E & de Biase, D 2018, 'Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4', Cancer Biomarkers, vol. 21, no. 2, pp. 323-334. https://doi.org/10.3233/CBM-170464
Masetti, Michele ; Acquaviva, Giorgia ; Visani, Michela ; Tallini, Giovanni ; Fornelli, Adele ; Ragazzi, Moira ; Vasuri, Francesco ; Grifoni, Daniela ; Di Giacomo, Simone ; Fiorino, Sirio ; Lombardi, Raffaele ; Tuminati, David ; Ravaioli, Matteo ; Fabbri, Carlo ; Bacchi-Reggiani, Maria Letizia ; Pession, Annalisa ; Jovine, Elio ; de Biase, Dario. / Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4. In: Cancer Biomarkers. 2018 ; Vol. 21, No. 2. pp. 323-334.
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T1 - Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4

AU - Masetti, Michele

AU - Acquaviva, Giorgia

AU - Visani, Michela

AU - Tallini, Giovanni

AU - Fornelli, Adele

AU - Ragazzi, Moira

AU - Vasuri, Francesco

AU - Grifoni, Daniela

AU - Di Giacomo, Simone

AU - Fiorino, Sirio

AU - Lombardi, Raffaele

AU - Tuminati, David

AU - Ravaioli, Matteo

AU - Fabbri, Carlo

AU - Bacchi-Reggiani, Maria Letizia

AU - Pession, Annalisa

AU - Jovine, Elio

AU - de Biase, Dario

PY - 2018/2/6

Y1 - 2018/2/6

N2 - BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection.OBJECTIVE: The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery.METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated.RESULTS: Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation.CONCLUSIONS: Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

AB - BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection.OBJECTIVE: The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery.METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated.RESULTS: Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation.CONCLUSIONS: Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

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DO - 10.3233/CBM-170464

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JO - Cancer Biomarkers

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