Expression of mismatch repair proteins, β catenin, and E cadherin in intestinal-type sinonasal adenocarcinoma

Abstract

Background: Despite their histological resemblance to colorectal adenocarcinomas, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). Aims: To evaluate the possible role of DNA mismatch repair (MMR) gene defects or disruptions of the E cadherin-b catenin complex in ITAC by investigating the immunohistochemical expression of the MMR gene products, b catenin, and E cadherin in a group of sporadic ITACs. Methods: Ten sporadic cases of ITAC were stained with antibodies against MLH1, MSH2, MSH3, MSH6, b catenin, and E cadherin. Results: Nine cases showed strong nuclear expression of MLH1, whereas one case showed moderate staining. All 10 cases were strongly positive for MSH2 and MSH3. MSH6 was strong in nine cases, and moderate in one. Membranous b catenin expression was strong in all 10 cases, and no case showed cytoplasmic or nuclear staining. E cadherin was strong in seven cases, and moderate in three cases. Conclusions: The preserved nuclear expression of MLH1, MSH2, MSH3, and MSH6 suggests that mutations or promoter methylation of MMR genes do not play a role in the pathogenesis of ITAC. The strong membranous staining for E cadherin and b catenin and lack of abnormal cytoplasmic or nuclear expression is in keeping with the preservation of E cadherin-b catenin complexes and b catenin pathways.

Establishment and genetic characterization of an immortal tumor cell line derived from intestinal-type sinonasal adenocarcinoma

“…The absence of nuclear β-catenin staining is in line with Perez Ordonez et al who found only membranous staining in all ten analyzed cases of ITAC [26]. However in one study, eight of 20 cases (40%) showed membranous, cytoplasmic and nuclear positivity [10].…”

“…Mutations in TP53, with a frequency of 60%-70% in CRC, ranged between 18% and 57% in ITAC [10,33,34], and 50% of loss of heterozygosity was detected at 17p13, the chromosomal locus of TP53 [27]. Other genetic alterations known in CRC, such as APC, β-catenin, p16 and mismatch repair genes were absent in ITAC [10,26,35]. Aiming for a genome-wide view of recurrent genetic abnormalities, CGH (Comparative Genomic Hybridization) and microarray CGH analysis have been performed and revealed frequent gains on chromosome arms 5p, 7q, 8q, 12p, and 20q, and losses on 4, 5q, 8p, 17p and 18q [2,11,17].…”

Genome‐wide analysis of genetic changes in intestinal‐type sinonasal adenocarcinoma

“…11 Further attempts to find genetic alterations as described in colorectal adenocarcinoma concerned APC, b-catenin, and various mismatch repair genes gave negative results. 10,15,17 These results indicate that ITAC and colorectal adenocarcinoma have different genetic pathways of development and progression.…”

Trail Overexpression Inversely Correlates with Histological Differentiation in Intestinal-Type Sinonasal Adenocarcinoma

“…The preserved nuclear expression of MLH1, MSH2, MSH3, and MSH6 suggested that mutations or promoter methylation of MMR genes do not play a role in the pathogenesis of ITAC [42]. …”