EGFR Signaling in Colorectal Carcinoma

The epidermal growth factor receptor (EGFR) and its downstream signaling pathways are involved in the development and progression of several human tumors, including colorectal cancer. Much attention has been given to the EGFR pathway as of lately because both EGFR and some downstream components serve as targets for anticancer therapy. In addition to playing a critical role in targeted therapy, alterations in this pathway can have prognostic implications. The EGFR pathway and its impact on colorectal carcinogenesis and prognosis are the emphasis of this paper. Since prognosis is tightly related to response to various therapies, the predictive value of the components of this pathway will be briefly discussed, but this is not the focus of this paper

Tubular adenoma with high-grade dysplasia in the ileal segment 34 years after augmentation ileocystoplasty: report of a first case

Neoplasms of the urinary bladder following augmentation ileocystoplasty are rare. We present the case of a 39-year-old male with a tubular adenoma with high-grade dysplasia in the ileal segment 34 years after augmentation ileocystoplasty to enlarge a post-chemoradiation-induced shrunken bladder. He presented with gross hematuria. Cystoscopy revealed a papillary tumor at the site of ileovesical anastomosis, and transurethral resection was performed. Histologic examination revealed a tubular adenoma with high-grade dysplasia. There are only two previous reports of tubulovillous adenoma in ileal segment after ileocystoplasty, both without high-grade dysplasia. Our observation supports the hypothesis that an ileal neobladder may undergo all the morphologic and molecular changes observed in the development of gastrointestinal adenocarcinoma. Therefore, patients who had an ileal neobladder created should be closely followed

The Cancer Genomics Resource List 2014

Context.— Genomic sequencing for cancer is offered by commercial for-profit laboratories, independent laboratory networks, and laboratories in academic medical centers and integrated health networks. The variability among the tests has created a complex, confusing environment. Objective.— To address the complexity, the Personalized Health Care (PHC) Committee of the College of American Pathologists proposed the development of a cancer genomics resource list (CGRL). The goal of this resource was to assist the laboratory pathology and clinical oncology communities. Design.— The PHC Committee established a working group in 2012 to address this goal. The group consisted of site-specific experts in cancer genetic sequencing. The group identified current next-generation sequencing (NGS)–based cancer tests and compiled them into a usable resource. The genes were annotated by the working group. The annotation process drew on published knowledge, including public databases and the medical literature. Results.— The compiled list includes NGS panels offered by 19 laboratories or vendors, accompanied by annotations. The list has 611 different genes for which NGS-based mutation testing is offered. Surprisingly, of these 611 genes, 0 genes were listed in every panel, 43 genes were listed in 4 panels, and 54 genes were listed in 3 panels. In addition, tests for 393 genes were offered by only 1 or 2 institutions. Table 1 provides an example of gene mutations offered for breast cancer genomic testing with the annotation as it appears in the CGRL 2014. Conclusions.— The final product, referred to as the Cancer Genomics Resource List 2014, is available as supplemental digital content

Fat, fibre and cancer risk in African Americans and rural Africans

Rates of colon cancer are much higher in African Americans (65: 100,000) than in rural South Africans (Peer reviewe

Fat, fibre and cancer risk in African Americans and rural Africans

Rates of colon cancer are much higher in African Americans (65: 100,000) than in rural South Africans (Peer reviewe

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

doi:10.4061/2011/932932 Review Article EGFR Signaling in Colorectal Carcinoma

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The epidermal growth factor receptor (EGFR) and its downstream signaling pathways are involved in the development and progression of several human tumors, including colorectal cancer. Much attention has been given to the EGFR pathway as of lately because both EGFR and some downstream components serve as targets for anticancer therapy. In addition to playing a critical role in targeted therapy, alterations in this pathway can have prognostic implications. The EGFR pathway and its impact on colorectal carcinogenesis and prognosis are the emphasis of this paper. Since prognosis is tightly related to response to various therapies, the predictive value of the components of this pathway will be briefly discussed, but this is not the focus of this paper. 1