3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability.

Next-generation Trop-2-targeted therapy against advanced cancers is hampered by expression of Trop-2 in normal tissues. We discovered that Trop-2 undergoes proteolytic activation by ADAM10 in cancer cells, leading to the exposure of a previously inaccessible protein groove flanked by two N-glycosylation sites. We designed a recognition strategy for this region, to drive selective cancer vulnerability in patients.

Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer.

We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models.

as an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: A Study with a Review of the Literature.

Background: GATA binding protein 3 () expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Thus, we undertook the current study to evaluate the expression of and its prognostic value in a large series of breast carcinomas (BCs) with long-term follow-up.

Methods: A total of 702 consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and , and scored.

Pre-operative management of Pleomorphic and florid lobular carcinoma in situ of the breast: Report of a large multi-institutional series and review of the literature.

Background: Pleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated.

Aim: To collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature.

HER2-Positive Lobular Versus Ductal Carcinoma of the Breast: Pattern of First Recurrence and Molecular Insights.

Background: Infiltrating lobular carcinoma (ILC) represents about 10% of breast cancer and rarely shows overexpression of human epidermal growth factor receptor 2 (HER2). We compared biological and clinical characteristics of HER2-positive ILC versus HER2-positive infiltrating ductal carcinoma (IDC).

Patients And Methods: We retrospectively analyzed the data of 328 patients with HER2-positive pure ductal or lobular breast carcinoma, comparing clinical and biological data at diagnosis as well as outcome between the 2 histologies.

High-sensitivity assay for monitoring ESR1 mutations in circulating cell-free DNA of breast cancer patients receiving endocrine therapy.

Approximately 70% of breast cancers (BCs) express estrogen receptor alpha (ERα) and are treated with endocrine therapy. However, the effectiveness of this therapy is limited by innate or acquired resistance in approximately one-third of patients. Activating mutations in the ESR1 gene that encodes ERα promote critical resistance mechanisms.

An international study comparing conventional versus mRNA level testing (TargetPrint) for ER, PR, and HER2 status of breast cancer.

To compare results from messenger RNA (mRNA)-based TargetPrint testing with those from immunohistochemistry (IHC) and in situ hybridization (ISH) conducted according to local standard procedures at hospitals worldwide. Tumor samples were prospectively obtained from 806 patients at 22 hospitals. The mRNA level of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was assessed by TargetPrint quantitative gene expression readouts.

Diagnostic and prognostic microRNAs in the serum of breast cancer patients measured by droplet digital PCR.

Background: Breast cancer circulating biomarkers include carcinoembryonic antigen and carbohydrate antigen 15-3, which are used for patient follow-up. Since sensitivity and specificity are low, novel and more useful biomarkers are needed. The presence of stable circulating microRNAs (miRNAs) in serum or plasma suggested a promising role for these tiny RNAs as cancer biomarkers.

Serologic investigation of undifferentiated nasopharyngeal carcinoma and simian virus 40 infection.

Background: The association between undifferentiated nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) is well established. Nevertheless, available evidence suggests that other cofactors are required for the development of undifferentiated NPC. Several investigations reported simian virus 40 (SV40) footprints in human tumors of different histotypes.

Trop-2 is a determinant of breast cancer survival.

Trop-2 is a calcium signal transducer that drives tumor growth. Anti-Trop-2 antibodies with selective reactivity versus Trop-2 maturation stages allowed to identify two different pools of Trop-2, one localized in the cell membrane and one in the cytoplasm. Of note, membrane-localized/functional Trop-2 was found to be differentially associated with determinants of tumor aggressiveness and distinct breast cancer subgroups.

miR-125b targets erythropoietin and its receptor and their expression correlates with metastatic potential and ERBB2/HER2 expression.

Background: The microRNA 125b is a double-faced gene expression regulator described both as a tumor suppressor gene (in solid tumors) and an oncogene (in hematologic malignancies). In human breast cancer, it is one of the most down-regulated miRNAs and is able to modulate ERBB2/3 expression. Here, we investigated its targets in breast cancer cell lines after miRNA-mimic transfection.

Treatment of a relapsing facial pyoderma gangrenosum (malignant pyoderma).

A case of rapidly relapsing pyoderma gangrenosum (PG) of the left preauricular area with no undermined borders is described. This might be considered a case of malignant pyoderma (PM), a rare variety of PG. Five months after complete healing obtained with systemic corticosteroids, the preauricular lesion of PG relapsed.

Cytoplasmic Trop-1/Ep-CAM overexpression is associated with a favorable outcome in node-positive breast cancer.

Objective: Trop-1/Ep-CAM modulates growth and survival of transformed cells, and it is highly expressed in most carcinomas including breast cancer. Only membranous staining is typically considered in evaluating Trop-1/epithelial cell adhesion molecule (Ep-CAM) expression in tumor cells. However, there is evidence of retention of Trop-1/Ep-CAM, as functionally incompetent molecules, in intra-cytoplasmic vesicles.

Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation.

In autosomal dominant polycystic kidney disease (ADPKD), renal cyst development and enlargement, as well as cell growth, are associated with alterations in several pathways, including cAMP and activator protein 1 (AP1) signalling. However, the precise mechanism by which these molecules stimulate cell proliferation is not yet fully understood. We now show by microarray analysis, luciferase assay, mutagenesis, and chromatin immunoprecipitation that CREB and AP1 contribute to increased expression of the amphiregulin gene, which codifies for an epidermal growth factor-like peptide, in ADPKD cystic cells, thereby promoting their cell growth.

Metastatic syringoid eccrine carcinoma of the nipple.

Syringoid eccrine carcinoma is a very rare skin tumor. Herein we describe a 72-year-old male patient presenting with a syringoid eccrine carcinoma of the nipple with associated axillary lymph node metastases. Surgery associated with adjuvant radiotherapy was performed.

MicroRNAs: toward the clinic for breast cancer patients.

Expression of microRNAs (miRNAs) has been found to be deregulated in all human cancers, where they may behave either as oncogenes or as tumor-suppressor genes. In the last 5 years, miRNA investigations in breast cancer represented an exciting area of discovery, which produced new knowledge on the molecular basis of this disease, tools for molecular classification, and new markers with diagnostic and prognostic relevance, as well as the discovery of novel breast cancer-predisposing genes. In this review, we describe current knowledge of the role of microRNAs in breast cancer.

MicroRNA profiling for the identification of cancers with unknown primary tissue-of-origin.

Cancer of unknown primary (CUP) represents a common and important clinical problem. There is evidence that most CUPs are metastases of carcinomas whose primary site cannot be recognized. Driven by the hypothesis that the knowledge of primary cancer could improve patient's prognosis, we investigated microRNA expression profiling as a tool for identifying the tissue of origin of metastases.

Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study.

Recent studies have reported the potential clinical utility for metastatic breast cancer (MBC) patients of continuing trastuzumab beyond progression. Based on those results, here the authors have examined the benefits of trastuzumab-continuation by specifically evaluating RECIST responses upon first line trastuzumab-treatment as a potential predictive marker for therapeutic effect of trastuzumab-continuation beyond metastatic disease progression. The authors carried out a retrospective analysis of 272 HER2 positive MBC patients under trastuzumab treatment at 22 different oncology Italian centers during the years of 2000 and 2001 who progressed under first line trastuzumab-treatment.

p53 status identifies two subgroups of triple-negative breast cancers with distinct biological features.

Objective: Despite the clinical similarities triple-negative and basal-like breast cancer are not synonymous. Indeed, not all basal-like cancers are negative for estrogen receptor, progesterone receptor and HER2 expression while triple-negative also encompasses other cancer types. P53 protein appears heterogeneously expressed in triple-negative breast cancers, suggesting that it may be associated with specific biological subgroups with a different outcome.

Oncogenic role of miR-483-3p at the IGF2/483 locus.

hsa-mir-483 is located within intron 2 of the IGF2 locus. We found that the mature microRNA (miRNA) miR-483-3p is overexpressed in 100% of Wilms' tumors. In addition, colon, breast, and liver cancers exhibit high or even extremely high levels of miR-483-3p in approximately 30% of the cases.

High expression of 90K (Mac-2 BP) is associated with poor survival in node-negative breast cancer patients not receiving adjuvant systemic therapies.

90K (Mac-2 BP) expression was evaluated by immunohistochemistry in paraffin-embedded tissue from a consecutive series of lymph-node negative breast cancer patients who did not receive adjuvant systemic treatment. An independent series of patients served as validation set. The association of 90K expression with risk of recurrence and death was examined in survival analyses together with known prognostic factors.

Sex hormone receptor levels in laryngeal carcinoma: a comparison between protein and RNA evaluations.

The larynx is a secondary sex organ, and the hormone dependence of laryngeal carcinomas is considered an interesting matter of speculation. However, while tumors of other secondary sex organs, including the prostate, breast, and endometrium, have been recognized as hormone-dependent cancers, the laryngeal carcinomas are still subject to controversy. In this study, samples from 15 laryngeal carcinomas obtained at the time of surgery were assayed for specific estrogen alpha, progesterone, and androgen receptor expression, both at mRNA and protein levels.