Claudin-1 positive proliferations in serrated colorectal polyps

Abstract

Aims To analyse the frequency of Claudin-1 positive proliferations in serrated colorectal polyps. Methods Consecutive colorectal polyps originally diagnosed as sessile serrated adenomas (SSAs) and large hyperplastic polyps were reviewed and reclassified as SSAs, microvesicular hyperplastic polyps (MVHP), or serrated polyps (SP) according to current diagnostic criteria. All polyps were assessed for BRAF V600E mutation using multiplex kits, tested for KRAS mutation, and had Claudin-1 immunohistochemistry performed. Results Of 377 cases, 174 were re-classified as SSAs, and 203 as MVHP/SP. Claudin-1 positive spindle cells were present in 9.3% (35/377). Twenty-four of 35 polyps with Claudin-1 positive stromal cells were SSAs, 9 were SP and 2 were MVHPs. Twenty-nine of the 35 Claudin-1 positive cases (82%) harboured BRAF V600E mutation. None of the polyps were KRAS positive. Discussion Perineural-like stromal proliferations have been recently described in 6.5% of BRAF V600E positive SSAs and intestinal perineuromas which are characterised by spindle cells obliterating lamina propria and expressing Claudin-1 protein. As SPs with BRAFV600E mutations are known to overexpress Claudin-1, demonstration of Claudin-1 in the stromal cells is a strong indication of epithelial-mesenchymal interactions in BRAF positive serrated polyps. Claudin-1 immunohistochemistry may also aid in diagnosing colorectal polyps containing spindle cells. To analyse the frequency of Claudin-1 positive proliferations in serrated colorectal polyps. Consecutive colorectal polyps originally diagnosed as sessile serrated adenomas (SSAs) and large hyperplastic polyps were reviewed and reclassified as SSAs, microvesicular hyperplastic polyps (MVHP), or serrated polyps (SP) according to current diagnostic criteria. All polyps were assessed for BRAF V600E mutation using multiplex kits, tested for KRAS mutation, and had Claudin-1 immunohistochemistry performed. Of 377 cases, 174 were re-classified as SSAs, and 203 as MVHP/SP. Claudin-1 positive spindle cells were present in 9.3% (35/377). Twenty-four of 35 polyps with Claudin-1 positive stromal cells were SSAs, 9 were SP and 2 were MVHPs. Twenty-nine of the 35 Claudin-1 positive cases (82%) harboured BRAF V600E mutation. None of the polyps were KRAS positive. Perineural-like stromal proliferations have been recently described in 6.5% of BRAF V600E positive SSAs and intestinal perineuromas which are characterised by spindle cells obliterating lamina propria and expressing Claudin-1 protein. As SPs with BRAFV600E mutations are known to overexpress Claudin-1, demonstration of Claudin-1 in the stromal cells is a strong indication of epithelial-mesenchymal interactions in BRAF positive serrated polyps. Claudin-1 immunohistochemistry may also aid in diagnosing colorectal polyps containing spindle cells.