Immunohistochemical staining for DNA mismatch repair proteins in intestinal tract XXXX : how reliable are biopsy samples?

@entity1 @entity6756 @entity41 @entity4309 @entity5 @entity189 @entity4311 @entity14437 @entity1820 @entity14 @entity420 @entity4638
BACKGROUND: In recent years, immunohistochemistry has emerged as an efficient tool in the detection of DNA mismatch repair protein abnormality in @entity14 . Currently, the immunohistochemical test is mainly applied to cancer resection specimens. Detection of mismatch repair abnormality in biopsies carries obvious clinical importance, as it would allow informed decision about the extent of surgery (segmental resection vs total colectomy, prophylactic hysterectomy or not). Moreover, in the case of treated @entity189 with no @entity41 , it provides a means to evaluate the mismatch repair proteins. However, whether biopsy samples can be reliably used for mismatch repair protein detection remains to be determined. MATERIALS AND METHODS: Paired biopsy and resection specimens of @entity420 of the gastrointestinal tract, enriched for @entity1 at increased risk for @entity4309 , were analyzed for immunohistochemical staining patterns for @entity6756 , @entity4311 , @entity4638 , and @entity14437 . Abnormal staining was defined as total loss of protein in the @entity5 with appropriate control. Cases with focal and weak staining, defined as staining of no more than moderate intensity present in <10% of the @entity5 cells, were recorded. Correlation analysis with germline mutation data was in a subset of cases. RESULTS: Among 70 @entity1820 (3 from the small bowel, 36 from the right colon, 15 from the left colon, and 16 from the anorectum), both the biopsy and resection specimens detected the same 29 @entity5 as having loss of staining for at least 1 protein, 14 affecting @entity6756 / @entity14437 and 15 affecting @entity4311 / @entity4638 . Focal and weak staining was most commonly seen for @entity6756 stain in biopsies (4 of 70, 6%), followed by @entity4638 stain in biopsies (3 of 70, 4%). Concordant staining patterns between biopsies and resections were reached in all 70 cases for @entity4311 and @entity14437 , whereas discordant patterns were identified in 3 cases (3 of 70, 4%) for @entity6756 and in 2 cases (2 of 70, 3%) for @entity4638 . None of the discordant patterns affected the final interpretation of whether the immunohistochemistry test was normal or abnormal in either the biopsy or the resection. In 13 of the 13 cases that were known to have a pathogenic germline mutation (5 in @entity6756 in @entity4311 ), the stains were abnormal for the corresponding protein and/or its partner protein in both the biopsy and the resection specimens. CONCLUSIONS: This study provides data indicating that biopsy samples are as reliable as resections in the immunohistochemical detection of mismatch repair protein abnormality in @entity5 . Our study also shows that various staining variations can occur in both biopsies and resections. Awareness and further understanding of such variations will enhance the use of immunohistochemistry, a commonplace tool that is being increasingly used in the screening workup for @entity4309 .
