Background: Recent studies have shown that minichromosome maintenance (MCM) proteins (Mcm2-7) may be useful proliferation markers in dysplasia and cancer in various tissues. Aims: To investigate the use of Mcm7 as a proliferation marker in 79 lymph node negative prostate cancers and compare it with Ki-67, a commonly used cell proliferation marker. Methods: The percentage of proliferating cells (proliferation index; PI) was calculated for basal and luminal epithelial cells in benign prostate tissue, prostatic intraepithelial neoplasia (PIN), and epithelial cells in adenocarcinoma. The PI for each biomarker was correlated with the preoperative prostate specific antigen concentration, the Gleason score, surgical resection margin status, and the AJCC pT stage for each patient. Results: The mean PIs for Ki-67 and Mcm7 were: benign luminal epithelium 0.7 and 1.2 and benign basal epithelium 0.8 and 8.2; PIN non-basal epithelium 4.9 and 10.6 and PIN basal epithelium 0.7 and 3.1; adenocarcinoma 9.8 and 22.7, respectively. Mcm7 had a significantly higher mean PI (p,0.0001) than Ki-67 for all cell categories except benign luminal epithelial cells. Mcm7 was a better discriminatory marker of proliferation between benign epithelium, PIN, and invasive adenocarcinoma (p,0.0001) than Ki-67. The drop in Mcm7 mean basal cell PI from benign epithelium to PIN epithelium was significantly larger than for Ki-67 (p,0.0001). Mcm7 had a significantly higher PI than Ki-67 at each risk level. Conclusion: Mcm7 may be a useful proliferation marker in prostatic neoplasia and warrants further evaluation as a complementary tool in the diagnosis of PIN and prostate carcinoma.

Context.-Immunohistochemistry (IHC) is important for cytology but poses special challenges because preanalytic conditions may differ from the conditions of IHC-positive controls.Objectives.-To broadly survey cytology laboratories to quantify preanalytic platforms for cytology IHC and identify problems with particular platforms or antigens. To discover how validation guidelines for HER2 testing have affected cytology.Design. Conclusions.-The platforms for cytology IHC and positive controls differ for most laboratories, yet conditions are uncommonly adjusted for cytology specimens. Except for the unsuitability of air-dried smears for HER2 testing, the survey did not reveal evidence of systematic problems with any antibody or platform. (Arch Pathol Lab Med. 2014;138:1167-1172 doi: 10.5858/arpa.2013-0259-CP) T he goal of cytology is to use the smallest possible biopsy for diagnosis, thereby reducing risk and discomfort for patients, facilitating population-based cancer detection programs, allowing faster diagnosis than can be achieved with larger biopsies, and saving money for the health care system. Even with large-sized surgical biopsies, immunohistochemistry (IHC) is often needed for the diagnosis and determination of prognostic markers. The cytology literature documents the suitability of cytology specimens for IHC 1 and the importance of IHC in allowing patients to realize the benefits of cytology.

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N-of-1 trials target actionable mutations, yet such approaches do not test genomically-informed therapies in patient tumor models prior to patient treatment. To address this, we developed patient-derived xenograft (PDX) models from fine needle aspiration (FNA) biopsies (FNA-PDX) obtained from primary pancreatic ductal adenocarcinoma (PDAC) at the time of diagnosis. Here, we characterize PDX models established from one primary and two metastatic sites of one patient. We identified an activating KRAS G12R mutation among other mutations in these models. In explant cells derived from these PDX tumor models with a KRAS G12R mutation, treatment with inhibitors of CDKs (including CDK9) reduced phosphorylation of a marker of CDK9 activity (phospho-RNAPII CTD Ser2/5) and reduced viability/growth of explant cells derived from PDAC PDX models. Similarly, a CDK inhibitor reduced phospho-RNAPII CTD Ser2/5, increased apoptosis, and inhibited tumor growth in FNA-PDX and patient-matched metastatic-PDX models. In summary, PDX models can be constructed from FNA biopsies of PDAC which in turn can enable genomic characterization and identification of potential therapies.

Biopsy specimens from the terminal ileum of 32 patients with the histopathological diagnosis of lymphocytic colitis or collagenous colitis and 11 control individuals were evaluated for the presence or absence of ileal mucosal abnormalities and for the number of intraepithelial lymphocytes, assessed by immunohistochemical stains for the pan T-cell marker, CD3. We found that the mean CD3 counts in patients with lymphocytic/collagenous colitis were significantly higher than those in the control group. Seven of 14 patients with collagenous colitis and 14 of 18 patients with lymphocytic colitis revealed an increase in intraepithelial T lymphocytes when compared with the control group (P ‫؍‬ .001). Other notable changes included ileal villous atrophy in one case of lymphocytic colitis and in three cases of collagenous colitis and epithelial damage with thickened subepithelial collagen in two cases of collagenous colitis.