Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colon cancer, particularly those that exhibit microsatellite instability. Distinguishing SSA/Ps from the related, but innocuous, microvesicular hyperplastic polyp (MVHP) can be challenging. In this study seven gastrointestinal pathologists reviewed 109 serrated polyps and identified 60 polyps with histological consensus. Microarray analysis was performed on six distal consensus MVHPs < 9 mm, six proximal consensus SSA/Ps > 9 mm, and six normal colon biopsies (three proximal, three distal). Comparative gene expression analysis confirmed the close relationship between SSA/Ps and MVHPs as there was overlapping expression of many genes. However, the gene expression profile in SSA/Ps had stronger and more numerous associations with cancer-related genes compared with MVHPs. Three genes (TFF2, FABP6, and ANXA10) were identified as candidates whose expression can differentiate SSA/Ps from MVHPs, and the differences in expression were confirmed by quantitative RT-PCR. As ANXA10 showed the most promise in differentiating these polyps, the expression of ANXA10 was evaluated by immunohistochemistry in consensus SSA/Ps (n = 26), MVHPs (n = 21), and normal colon (n = 9). Immunohistochemical expression of ANXA10 was not identified in separate samples of normal colon or in the normal colonic epithelium adjacent to the serrated polyps. Consistent with the microarray and quantitative RT-PCR experiments, immunohistochemical expression of ANXA10 was markedly increased in SSA/Ps compared to MVHPs (p < 0.0001). An ANXA10 score ≥ 3 has a sensitivity of 73% and a specificity of 95% in the diagnosis of an SSA/P. In conclusion, we show that SSA/Ps and MVHPs have significant overlap in gene expression, but also important differences, particularly in cancer-related pathways. Expression of ANXA10 may be a potential marker of the serrated pathway to colon cancer.

Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.

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Reading acquisition was related to phonological sensitivity and rapid naming in a longitudinal study with young children. Phonological assessment consisted of rhyme and initial consonant discrimination, while the rapid naming tasks were made up of pictures, letters, and numbers. The subjects were 95 children from two grade levels, primary and first grade. They were tested in the fall and spring of the first year and the spring of the second year. It was found that the phonological and rapid naming tests each predicted unique variance in reading attainment, as measured at the end of the second year of the study. The rapid naming responses became more automatic early in the first grade year, while naming times generally became faster. Although many researchers regard rapid naming as part of the phonological core, the present article discusses the various advantages of considering rapid naming as a separate factor in reading development.

TMPRSS2-ERG, the most common gene fusion in prostate cancer, is associated with expression of a truncated protein product of the oncogene ERG. A novel anti-ERG monoclonal antibody has been recently characterized. We investigated the correlation between ERG rearrangement assessed by fluorescence in situ hybridization (FISH) and ERG expression detected by immunohistochemistry in a large cohort of patients treated with radical prostatectomy for clinically localized prostate cancer. Thirteen tissue microarrays comprising 305 tumors and a subset of 112 samples of nonneoplastic prostatic tissue were assessed for ERG rearrangement status by FISH and for ERG expression by immunohistochemistry. Accuracy of ERG detection by immunohistochemistry in predicting ERG status as assessed by FISH (criterion standard) was calculated in terms of sensitivity, specificity, positive and negative predictive values. Of 305 tumor foci, 103 (34%) showed ERG rearrangement by FISH. ERG was detected by immunohistochemistry in 100 (33%) cases, 99 of which were FISH positive. ERG detection by immunohistochemistry demonstrated a sensitivity and specificity of 96% and 99%, respectively, with positive and negative predictive values of 99% and 98%, respectively. None of the 112 samples of nonneoplastic prostatic tissue was rearranged by FISH or showed any ERG expression. In conclusion, ERG detection by immunohistochemistry in prostate cancer was highly predictive of ERG rearrangement as assessed by FISH in a large cohort of prostatectomy patients. Given the high yield and the easier task of performing immunohistochemistry vs. FISH, ERG assessment by immunohistochemistry may be useful for characterizing ERG status in prostate cancer.