Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK.

Thirty-three small "flat adenomas," not more than 1 cm in diameter, were collected from surgically and colonoscopically removed specimens, and their colonoscopic and histologic characteristics were described. There were 14 adenomas with mild atypia, five with moderate atypia, 14 with severe atypia (or focal carcinoma limited to the mucosa). The grade of atypia seems to increase with the size of lesions, and these lesions were assumed to play an important role in the adenoma-carcinoma sequence. The importance of recognizing the presence of these small "flat adenomas" in everyday practice is stressed.

Small "flat adenoma" of the large bowel with special reference to its clinicopathologic features.

The growth type of early colorectal carcinoma was classified into two types. The first type is intramucosal polypoid growth (PG-Ca) and the second type nonpolypoid growth (NPG-Ca) which shows mainly massive infiltration of tumor cells below the submucosal layer. The incidence of adenoma-carcinoma sequence was 72 of 75 lesions (96.0%) in pedunculated polypoid carcinoma, and 61 of 71 lesions (85.9%) in sessile and broad-based polypoid carcinomas. Their average sizes were 15.0 and 18.7 mm, respectively. Submucosal invasive carcinoma (SM-Ca) showed a low incidence. They were detected as microscopical or scattered lesions with a few lymphatic and venous permeation. The NPG-Ca contained 32 lesions. Intramucosal carcinoma without adenoma showing slight depression consisted of ten lesions of which the average size was 5.1 mm. The other 22 lesions showed massive submucosal invasion with marked lymphatic and venous permeation. The average size was 10.3 mm being smaller than PG-Ca. Histologically, NPG-Ca was not accompanied with adenoma. The NPG-Ca arose from de novo carcinoma less than 10 mm in diameter and invaded into the submucosal layer. In advanced carcinoma, the PG-Ca showed a low incidence (21.8%), and almost all cases were of the NPG type (78.2%). The NPG advanced carcinomas increased in those over the size of 20 mm. It is concluded that nonpolypoid early colorectal carcinomas easily progress to advanced carcinoma, and de novo carcinoma occupied about 80% of colorectal carcinoma.

Early colorectal carcinoma with special reference to its development de novo

Background While the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumour virus (MMTV), bovine leukaemia virus (BLV), human papilloma viruses (HPVs) and Epstein Barr virus (EBV – also known as herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence. The evidence MMTV and human breast cancer -the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer- the evidence is limited. However in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer -the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer -the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal. Conclusion The influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

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Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein-Barr Virus (EBV).

Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined.

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The Regulation of Steroid Action by Sulfation and Desulfation

Two small carcinomas of the colon were examined, one an intramucosal carcinoma and the other a small carcinoma invading the submucosa. Serial sections did not reveal any adenomatous hyperplasia or polyps in the vicinity. The colonoscopist must be aware of the potential clinical importance of any small mucosal excrescence. Although several studies have indicated that most colonic carcinomas develop from an adenomatous polyp, some carcinomas apparently arise de novo. Further study of the epidemiologic, etiologic, and prognostic factors relating to these apparently uncommon lesions is indicated.

Small nonpolypoid carcinomas of the large intestine.

In this paper, I report a rare, low-grade malignant tumor, solid and papillary epithelial neoplasm of the pancreas (SPENP). I also discuss and review 157 previously reported cases. Unlike other malignant tumors of the pancreas, this neoplasm is typically found in young women, does not have metastases, and is amenable to cure after complete surgical resection. I discuss clinical features, diagnostic procedures, and differential diagnosis. Fine-needle aspiration can be effective in obtaining a preoperative diagnosis of SPENP, since the tumor has characteristic cytologic features. Also, use of clinical data, ultrasonography studies, computed tomography, magnetic resonance imaging, arteriography, and cytologic findings in the preoperative workup are important in obtaining an accurate diagnosis. Although potentially curable, late metastases and current inability to predict aggressive behavior by some tumors require lengthy follow-up.

Solid and papillary epithelial neoplasm of the pancreas, diagnosis by cytology.

Purpose: The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men. Experimental Design: We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age- and tumor grade–matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored. Results: Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen-regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo . Conclusions: Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men. Clin Cancer Res; 22(7); 1744–56. ©2015 AACR .

https://clincancerres.aacrjournals.org/content/clincanres/22/7/1744.full.pdf

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

OBJECTIVE AND IMPORTANCE: Only two cases of primary intracranial myxomas have been described previously in the literature: one patient had a primary intracranial myxoma in the pituitary fossa, and the other patient's myxoma was located in the posterior fossa.

Primary Myxoma of the Temporal Bone in a 17-Year-Old Boy: Case Report

Although estrogen receptor beta (ERβ) has been implicated in prostate cancer (PCa) progression, its potential role in health disparity of PCa remains elusive. The objective of this study was to examine serum estrogens and prostate tumor ERβ expression and examine their correlation with clinical and pathological parameters in African American (AA) versus Caucasian American (CA) men. The circulating 17β-estradiol (E2) was measured by enzyme immunoassay in blood procured from racially stratified normal subjects and PCa patients. Differential expression profile analysis of ERβ was analyzed by quantitative immunohistochemistry using ethnicity-based tissue microarray encompassing 300 PCa tissue cores. In situ ERβ expression was validated by quantitative reverse transcription-PCR in matched microdissected normal prostate epithelium and tumor cells and datasets extracted from independent cohorts. In comparison with normal age-matched subjects, circulating E2 levels were significantly elevated in all PCa patients. Further analysis demonstrates an increase in blood E2 levels in AA men in both normal and PCa in comparison with age- and stage-matched counterparts of CA decent. Histochemical score analysis reveals intense nuclear immunoreactivity for ERβ in tumor cores of AA men than in CA men. Gene expression analysis in microdissected tumors corroborated the biracial differences in ERβ expression. Gene expression analysis from independent cohort datasets revealed correlation between ERβ expression and PCa progression. However, unlike in CA men, adjusted multivariate analysis showed that ERβ expression correlates with age at diagnosis and low prostate-specific antigen recurrence-free survival in AA men. Taken together, our results suggest that E2-ERβ axis may have potential clinical utility in PCa diagnosis and clinical outcome among AA men.

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Byron Crawford

Papers

Small nonpolypoid carcinomas of the large intestine.

Solid and papillary epithelial neoplasm of the pancreas, diagnosis by cytology.

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

Primary Myxoma of the Temporal Bone in a 17-Year-Old Boy: Case Report

High circulating estrogens and selective expression of ERβ in prostate tumors of Americans: implications for racial disparity of prostate cancer