Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent.

The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages.

Micropapillary urothelial carcinoma of urinary bladder displays immunophenotypic features of luminal and p53-like subtypes and is not a variant of adenocarcinoma.

Objectives: Micropapillary urothelial carcinoma of the urinary bladder (MPUC) is a rare variant of urothelial carcinoma which has aggressive clinical characteristics. The objective is to investigate the molecular subtypes of MPUC and the impact to the clinical outcome and determine whether MPUC represents a variant of adenocarcinoma.

Materials And Methods: We evaluated surrogate immunohistochemical markers of luminal, basal, and p53-like subtypes and correlated with prognosis and the expression of markers related to bladder adenocarcinoma and glandular differentiation in 56 cases of MPUC (10 cases of transurethral resection and 46 cases of radical cystectomy).

TERT promoter mutation status in sarcomatoid urothelial carcinomas of the upper urinary tract.

Aim: To determine TERT promoter mutation status as well as the expression of PAX8, GATA3, p63, p40, p53 and uroplakin III in 17 patients with the upper urinary tract sarcomatoid urothelial carcinoma.

Methods & Results:  TERT C228T mutations were found in six of 17 cases (35%). p53 was expressed in 77% of these tumors.

Significance of Programmed Death Ligand 1 (PD-L1) Immunohistochemical Expression in Colorectal Cancer.

Introduction: The significance of programmed death ligand 1 (PD-L1) expression in the prognosis of patients with colorectal cancer remains to be determined.

Methods: We assessed the levels of PD-L1 expression in tumor-infiltrating immune cells as well as tumor cells, and evaluated the association between PD-L1 expression and clinical outcome in 262 colorectal cancer patients.

Results: In univariate analysis, TNM stage (p < 0.

Tubulocystic renal cell carcinoma is an entity that is immunohistochemically and genetically distinct from papillary renal cell carcinoma.

Aims: Some studies have suggested that tubulocystic carcinoma may be related to papillary renal cell carcinoma. We sought to compare and contrast the molecular and immunohistochemical profiles of tubulocystic carcinoma with those of papillary renal cell carcinoma.

Methods And Results: Twelve cases of pure tubulocystic renal cell carcinoma were subjected to fluorescence in-situ hybridization assessment of chromosomal number for chromosomes 7 and 17, and for TFE3 translocation.

Inflammatory myofibroblastic tumour of the urinary bladder: the role of immunoglobulin G4 and the comparison of two immunohistochemical antibodies and fluorescence in-situ hybridization for the detection of anaplastic lymphoma kinase alterations.

Aims: We examined gene rearrangement and the expression of anaplastic lymphoma kinase (ALK) in urinary bladder inflammatory myofibroblastic tumour (IMT) using fluorescence in-situ hybridization (FISH) and two immunohistochemical antibodies to ALK. We also investigated whether IMT represents an immunoglobulin (Ig)G4-related disease.

Methods And Results: The performance of the Dako FLEX ALK monoclonal antibody (CD246) and the Cell Signaling Technology ALK (D5F3) XP monoclonal antibody were compared.

Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma.

Small cell carcinoma of the prostate (PSCC) is a highly aggressive malignancy that often develops in patients previously treated with hormonal therapy for metastatic prostatic acinar adenocarcinoma. The TMPRSS2-ERG gene rearrangement is highly specific for prostate cancer and shared by PSCC; however, the role of androgen receptor (AR) gene alterations and interaction with TMPRSS2-ERG rearrangement are incompletely understood in PSCC. Sixty-one cases of PSCC were examined for AR gene copy number and TMPRSS2-ERG rearrangement by fluorescence in situ hybridization (FISH) and AR protein expression by immunohistochemistry.

Molecular subtyping of metastatic renal cell carcinoma: implications for targeted therapy.

Background: Renal cell carcinoma (RCC) is known for its ability to metastasize synchronously or metachronously to various anatomic sites. Distinguishing histologic subtypes of metastatic RCC has become increasingly important, as prognosis and therapy can differ dramatically between subtypes. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping metastatic RCC in light of these potential therapeutic implications.

Gastroesophageal junction adenocarcinoma displays abnormalities in homologous recombination and nucleotide excision repair.

Objective: Esophageal adenocarcinoma (EAC) continues to be a disease associated with high mortality. Among the factors leading to poor outcomes are innate resistance to currently available therapies, advanced stage at diagnosis, and complex biology. Platinum and ionizing radiation form the backbone of treatment for the majority of patients with EAC.

Atypical adenomatous hyperplasia of prostate lacks TMPRSS2-ERG gene fusion.

Atypical adenomatous hyperplasia (AAH) is a distinct entity in prostate pathology, defined as a well-circumscribed lobule of closely packed crowded small glands or acini. Although it has been proposed as a precursor lesion to prostate cancer, the biological nature of AAH is currently uncertain. The TMPRSS2-ERG fusion gene is a common recurrent chromosomal rearrangement in prostate cancer and in its precursor lesion, prostatic intraepithelial neoplasia.

Frequent TMPRSS2-ERG rearrangement in prostatic small cell carcinoma detected by fluorescence in situ hybridization: the superiority of fluorescence in situ hybridization over ERG immunohistochemistry.

Small cell carcinoma of the prostate is both morphologically and immunohistochemically similar to small cell carcinoma of other organs such as the urinary bladder or lung. TMPRSS2-ERG gene fusion appears to be a highly specific alteration in prostatic carcinoma that is frequently shared by small cell carcinoma. In adenocarcinoma, immunohistochemistry for the ERG protein product has been reported to correlate well with the presence of the gene fusion, although in prostatic small cell carcinoma, this relationship is not completely understood.

Novel markers of squamous differentiation in the urinary bladder.

Urinary bladder squamous cell carcinoma and urothelial carcinoma with squamous differentiation are often high-grade and high-stage tumors that are thought to be associated with a poorer prognosis and response to therapy compared with urothelial carcinoma without divergent differentiation. Therefore, recognition of a squamous component is increasingly important in guiding prognosis and therapy. We investigated the expression of MAC387, desmoglein-3, and TRIM29 in pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation to determine whether they have utility as diagnostic biomarkers for squamous differentiation.

Clear cell papillary renal cell carcinoma-like tumors in patients with von Hippel-Lindau disease are unrelated to sporadic clear cell papillary renal cell carcinoma.

Clear cell papillary renal cell carcinoma (CCPRCC) shares morphologic overlap with clear cell renal cell carcinoma, although it lacks chromosome 3p and VHL gene abnormalities. Rare cases have been reported in von Hippel-Lindau (VHL) patients (germline mutation of the VHL gene), the significance of which is uncertain. We analyzed morphologic, immunohistochemical, and molecular features in 14 CCPRCC-like tumors and 13 clear cell renal cell carcinomas from 12 patients with VHL disease.

Distinguishing primary adenocarcinoma of the urinary bladder from secondary involvement by colorectal adenocarcinoma: extended immunohistochemical profiles emphasizing novel markers.

Glandular neoplasms involving the urinary bladder carry a challenging differential diagnosis including primary and secondary processes. We investigated the potential diagnostic utility of cadherin-17 and GATA3 in 25 primary adenocarcinomas of the urinary bladder, as compared with other commonly used markers including β-catenin and p63. Urothelial carcinoma with glandular differentiation (11), colorectal adenocarcinoma secondarily involving the bladder (25), and primary colorectal adenocarcinoma (22) were also analyzed and the results were compared using a Fisher exact test.

Mushroom Ganoderma lucidum prevents colitis-associated carcinogenesis in mice.

Background: Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice.

Multilocular cystic renal cell carcinoma: similarities and differences in immunoprofile compared with clear cell renal cell carcinoma.

Multilocular cystic renal cell carcinoma (RCC) is an uncommon renal neoplasm composed of thin fibrous septa lining multiple cystic spaces and associated with an excellent prognosis. Clear cells with generally low-grade nuclear features line the cystic spaces and may be present within the fibrous septa, although solid mass-forming areas are by definition absent. Despite the excellent prognosis, molecular-genetic alterations are similar to those of clear cell RCC.

Value of the first post-transplant biopsy for predicting long-term cardiac allograft vasculopathy (CAV) and graft failure in heart transplant patients.

Background: Cardiac allograft vasculopathy (CAV) is the principal cause of long-term graft failure following heart transplantation. Early identification of patients at risk of CAV is essential to target invasive follow-up procedures more effectively and to establish appropriate therapies. We evaluated the prognostic value of the first heart biopsy (median: 9 days post-transplant) versus all biopsies obtained within the first three months for the prediction of CAV and graft failure due to CAV.

Lymphoepithelioma-like carcinoma of the urinary bladder: clinicopathologic, immunohistochemical, and molecular features.

Introduction: Lymphoepithelioma-like carcinoma (LELC) in the urinary tract is a rare malignancy, named for its resemblance to nasopharyngeal undifferentiated carcinoma or lymphoepithelioma. Investigation of immunohistochemical and molecular characteristics of bladder LELC is limited. The pathogenesis and biological behavior of these tumors are controversial.

Triterpenes from Ganoderma Lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase (p38 MAPK).

Medicinal mushroom Ganoderma lucidum is one of the most esteemed natural products that have been used in the traditional Chinese medicine. In this article, we demonstrate that G. lucidum triterpene extract (GLT) suppresses proliferation of human colon cancer cells HT-29 and inhibits tumor growth in a xenograft model of colon cancer.

TP53 mutational analysis supports monoclonal origin of biphasic sarcomatoid urothelial carcinoma (carcinosarcoma) of the urinary bladder.

Sarcomatoid urothelial carcinoma of the urinary bladder is an uncommon neoplasm with biphasic morphology exhibiting both epithelial and sarcomatoid components. Whether this tumor arises from a single cancer stem cell with subsequent differentiation or represents collision of the progeny of two separate cancer stem cells is a matter of controversy. To clarify its clonal origin, we analyzed the TP53 mutation status of a series of 17 sarcomatoid urothelial carcinomas using single-strand conformation polymorphism, DNA sequencing and p53 immunohistochemistry.

Sarcomatoid carcinoma of the upper urinary tract: clinical outcome and molecular characterization.

Sarcomatoid carcinoma (carcinosarcoma) of the upper urinary collecting system is a rare aggressive malignancy composed of malignant epithelial and stromal components. Because of the paucity of reported cases, the clinical behavior, molecular alterations, and potential therapies for this malignancy are not well understood. Eight cases of sarcomatoid carcinoma involving the upper urinary tract were studied.

Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis : a Hoosier Oncology Group trial.

Background: Ovarian tumors frequently express c-Kit and/or platelet-derived growth factor receptors (PDGFRs). Imatinib mesylate blocks the growth of ovarian cancer cells in vitro and may enhance the activity of chemotherapy. This study was conducted to determine the activity of imatinib in combination with docetaxel in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC).

Epidermal growth factor receptor (EGFR) expression in prostatic adenocarcinoma after hormonal therapy: a fluorescence in situ hybridization and immunohistochemical analysis.

Background: The progression of normal prostatic epithelium to androgen-dependent cancer and, eventually, hormone-refractory prostate cancer is a complex process involving many different growth regulatory signals. Activation of epidermal growth factor receptor (EGFR) has been implicated in prostate cancer cell growth.

Methods: This study was undertaken to investigate both amplification of EGFR gene by fluorescence in situ hybridization (FISH) and over-expression of EGFR by immunohistochemical staining in prostate tissue from 71 patients treated by hormonal therapy.

Germ cell origin of testicular carcinoid tumors.

Purpose: Carcinoids are neuroendocrine tumors and most frequently occur within tissues derived from the embryonic gut. These tumors can occur in any organ site but are rare in the testis. The cell type giving rise to testicular carcinoid is unknown.