Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma

Fei Bao, Nicole C. Panarelli, Hanna Rennert, David L. Sherr, Rhonda K. Yantiss

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Immunohistochemical stains are routinely used to detect abnormal DNA mismatch repair (MMR) protein expression in colorectal carcinomas, particularly when Lynch syndrome is suspected. Complete loss of MMR protein expression is often associated with underlying microsatellite instability (MSI), and the combined results of mutL homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), mutS homolog 2 (MSH2), or mutS homolog 6 (MSH6) immunostains may point to the defective MMR protein in tumors with MSI. We have noted that some neoadjuvantly treated colorectal carcinomas display loss of MMR protein immunoexpression, despite a lack of underlying MSI and preserved staining in pretreatment tumor samples. The purpose of this study was to determine the frequency of this finding. We identified 51 neoadjuvantly treated resected colorectal cancers. Posttreatment tumor samples were immunohistochemically stained with MLH1, PMS2, MSH2, and MSH6 antibodies. Loss of staining for any marker was followed by analysis for MSI and assessment of MMR protein expression in pretreatment tumor samples. All of the 51 posttreatment tumor samples showed preserved MLH1, PMS2, and MSH2, but 10 posttreatment tumor samples (20%) showed decreased MSH6 staining. Of these, 9 posttreatment tumor samples displayed loss of staining in less than 100% of tumor cells, but preserved MSH6 expression in pretreatment tumor samples. One case showed a complete absence of MSH6 staining in both pretreatment and posttreatment tumor samples. All 10 cases were microsatellite stable. We conclude that extensive loss of MSH6 immunoexpression is common among neoadjuvantly treated colorectal carcinomas, but generally does not reflect underlying MSI. Therefore, diminished MSH6 staining in treated tumors should prompt immunohistochemical evaluation of pretreatment biopsy samples before genetic testing for Lynch syndrome.

Original languageEnglish (US)
Pages (from-to)1798-1804
Number of pages7
JournalAmerican Journal of Surgical Pathology
Volume34
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

Fingerprint

Neoadjuvant Therapy
Colorectal Neoplasms
Microsatellite Instability
DNA Mismatch Repair
Neoplasms
Staining and Labeling
Hereditary Nonpolyposis Colorectal Neoplasms
Proteins
Genetic Testing
Microsatellite Repeats
Coloring Agents

Keywords

  • hereditary nonpolyposis colorectal cancer
  • immunohistochemistry
  • Lynch syndrome
  • microsatellite instability
  • mismatch repair

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma. / Bao, Fei; Panarelli, Nicole C.; Rennert, Hanna; Sherr, David L.; Yantiss, Rhonda K.

In: American Journal of Surgical Pathology, Vol. 34, No. 12, 12.2010, p. 1798-1804.

Research output: Contribution to journalArticle

Bao, Fei ; Panarelli, Nicole C. ; Rennert, Hanna ; Sherr, David L. ; Yantiss, Rhonda K. / Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma. In: American Journal of Surgical Pathology. 2010 ; Vol. 34, No. 12. pp. 1798-1804.
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