Given the benefit of epidermal growth factor receptor (EGFR) monoclonal antibodies in colorectal cancer (CRC), we sought to evaluate the efficacy of panitumumab in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC).
Anti-EGFR targeted therapy could be applied to about two-thirds of small intestinal adenocarcinoma patients, namely those with wild-type KRAS and BRAF if they have metastatic disease, similar to colorectal cancer patients.
Targeted therapy, against the angiogenic pathway or the epidermal growth factor receptor (EGFR) pathway, for example, is not yet established, but seems promising given the over-expression of vascular epithelial growth factor (VEGF)-A or EGFR observed in SBA.
This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations.
Thus, routine immunohistochemical and/or FISH testing for HER2 for potential targeted anti-HER2 therapy may not be beneficial for patients with primary small intestinal adenocarcinoma.
Small Bowel Adenocarcinoma Frequently Exhibits Lynch Syndrome-associated Mismatch Repair Protein Deficiency But Does Not Harbor Sporadic MLH1 Deficiency.
In conclusion, we established an SBA cell line with molecular characteristics similar to those of clinical SBA samples, including β-catenin deletion and mismatch repair protein deficiency, that will be useful for SBA research.
This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations.
In order to elucidate the molecular background of beta-catenin stabilization in small intestinal adenocarcinoma, we investigated 20 non-familial adenomatous polyposis coli (FAP)-associated tumours, including five microsatellite-unstable carcinomas for beta-catenin alterations, by immunohistochemistry, western blot analysis and sequence analysis on the RNA and DNA levels.
Cutaneous (eight sebaceous adenomas, one sebaceous carcinoma and one keratoacanthoma) and internal tumors (four colonic adenocarcinomas, two endometrial carcinomas, two transitional cell carcinomas of renal pelvis and ureter, one adenocarcinoma of the small bowel, one ovarian carcinoma and one colonic tubular adenoma) were obtained from six patients with MTS and were subjected to microsatellite instability (MI) analysis, and to immunostaining for MLH-1 and MSH-2.
Abnormal expression of E-cadherin and beta-catenin was common and reflects an early alternative to APC in this pathway in which mutations may be found in adenocarcinoma of the small intestine.
Multivariate survival analysis revealed that the combined loss of USP10 and p14ARF expression could be an independent prognostic factor for overall survival in small intestinal adenocarcinoma.
Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4.
Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4.
We analyzed a consecutive series of 71 small bowel adenocarcinomas identified over an 8-year period for DNA mismatch repair (MMR) protein expression to (1) compare the clinicopathologic features of small bowel adenocarcinoma stratified into MMR-deficient (MMRD) and MMR-proficient (MMRP) groups and (2) examine the patterns of MMR protein expression in small bowel adenocarcinoma compared with colorectal carcinoma.
The positive frequencies of PI3K and p-Akt expression were significantly higher in the SIA group (77.4%, 41/53 and 77.4%, 41/53, respectively) than that in the non-cancer group (36.4%, 4/11 and 27.3, 3/11, respectively) and normal small intestine tissue group (36.4%, 4/11 and 18.2, 2/11, respectively).