Defective DNA mismatch repair in long-term (≥ 3 years) survivors with pancreatic cancer

John T. Maple, Thomas Christopher Smyrk, Lisa Allyn Boardman, Ruth A. Johnson, Stephen N Thibodeau, Suresh T Chari

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background/Aims: Defective DNA mismatch repair (MMR) in pancreatic cancer, reported in up to 13% of sporadic pancreatic cancers, may predict a good prognosis. To determine if long-term survival in pancreatic cancer could be attributed to defective DNA MMR, we ascertained its prevalence in 35 pancreatic cancer patients who survived ≥ 3 years after surgery. Methods: We performed immunohistochemistry (IHC) for MMR proteins hMLH1, hMSH2, and hMSH6 in all 35 tumors and microsatellite instability (MSI) studies in 34/35 tumors using 10 microsatellite markers in paired normal and tumor DNA. Defective DNA MMR was defined as absence of protein expression on IHC and/or MSI in ≥ 30% of markers studied. Results: On IHC, 3/35 (8.6%) tumors had defective DNA MMR. All 3 had absent expression of a DNA MMR protein (hMLH1 in 2 and hMSH2) and 2/3 also had MSI; the third could not be tested. Definitely 2, and probably all 3 patients had hereditary non-polyposis colon cancer as determined by clinical and genetic profiles. Conclusion: Defective DNA MMR is uncommon in long-term survivors of pancreatic cancer and does not account for the survival benefit in those with sporadic pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)220-227
Number of pages8
JournalPancreatology
Volume5
Issue number2-3
DOIs
StatePublished - 2005

Fingerprint

DNA Mismatch Repair
Pancreatic Neoplasms
Survivors
Microsatellite Instability
Immunohistochemistry
Neoplasms
Proteins
Survival
Microsatellite Repeats
Colonic Neoplasms
DNA

Keywords

  • DNA mismatch repair
  • hHMSH2
  • hMLH1
  • Microsatellite instability
  • Pancreatic neoplasms
  • Prognosis

ASJC Scopus subject areas

  • Endocrinology
  • Gastroenterology

Cite this

Defective DNA mismatch repair in long-term (≥ 3 years) survivors with pancreatic cancer. / Maple, John T.; Smyrk, Thomas Christopher; Boardman, Lisa Allyn; Johnson, Ruth A.; Thibodeau, Stephen N; Chari, Suresh T.

In: Pancreatology, Vol. 5, No. 2-3, 2005, p. 220-227.

Research output: Contribution to journalArticle

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abstract = "Background/Aims: Defective DNA mismatch repair (MMR) in pancreatic cancer, reported in up to 13{\%} of sporadic pancreatic cancers, may predict a good prognosis. To determine if long-term survival in pancreatic cancer could be attributed to defective DNA MMR, we ascertained its prevalence in 35 pancreatic cancer patients who survived ≥ 3 years after surgery. Methods: We performed immunohistochemistry (IHC) for MMR proteins hMLH1, hMSH2, and hMSH6 in all 35 tumors and microsatellite instability (MSI) studies in 34/35 tumors using 10 microsatellite markers in paired normal and tumor DNA. Defective DNA MMR was defined as absence of protein expression on IHC and/or MSI in ≥ 30{\%} of markers studied. Results: On IHC, 3/35 (8.6{\%}) tumors had defective DNA MMR. All 3 had absent expression of a DNA MMR protein (hMLH1 in 2 and hMSH2) and 2/3 also had MSI; the third could not be tested. Definitely 2, and probably all 3 patients had hereditary non-polyposis colon cancer as determined by clinical and genetic profiles. Conclusion: Defective DNA MMR is uncommon in long-term survivors of pancreatic cancer and does not account for the survival benefit in those with sporadic pancreatic cancer.",
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