Unraveling the protein kinase C/NDRG1 signaling network in breast cancer.

N-myc downstream-regulated gene 1 (NDRG1) is a member of the NDRG family of intracellular proteins and plays a central role in a wide range of biological processes including stress response, differentiation, and metabolism. The overexpression of NDRG1 is an indicator of poor prognosis in various types of cancer. Here, we found that NDRG1 is an independent prognostic marker of poor outcome in breast cancer (BC).

VEGFA Status as a Predictive Marker of Therapy Outcome in Metastatic Gastric Cancer Patients Following Ramucirumab-Based Treatment.

Metastatic gastric cancer (mGC) often has a poor prognosis and may benefit from a few targeted therapies. Ramucirumab-based anti-angiogenic therapy targeting the VEGFR2 represents a milestone in the second-line treatment of mGC. Several studies on different cancers are focusing on the major VEGFR2 ligand status, meaning VEGFA gene copy number and protein overexpression, as a prognostic marker and predictor of response to anti-angiogenic therapy.

De-Implementation of Axillary Staging and Radiotherapy in Low-Risk Breast Cancer Patients Aged 70-79 Years from Six Italian Cancer Institutes.

In women aged ≥70 with low-risk breast cancer (BrC), some major international guidelines recommend against sentinel lymph node biopsy (for example, those from the Society of Surgical Oncology, U.S.) and post-lumpectomy radiotherapy (for example, those from the National Comprehensive Cancer Network, U.

Downstream Signaling of Inflammasome Pathway Affects Patients' Outcome in the Context of Distinct Molecular Breast Cancer Subtypes.

Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization.

The role of rapid on site evaluation on touch imprint cytology and brushing during conventional bronchoscopy.

Background: The increase in immunohistochemical and molecular predictive tests in lung cancer requires new strategies for managing small samples taken during bronchoscopic procedures. The value of Rapid On Site Evaluation (ROSE) during conventional bronchoscopic procedures on endobronchial neoplasms in optimizing small biopsies and cytologlogical tissue specimens for diagnostic testing, and ancillary studies was evaluated.

Method: ROSE on touch imprint cytology (TIC) and brushing was performed on 690 consecutive cases of patients undergoing biopsies, using fiber optic bronchoscopy.

Tumor Infiltrating Lymphocytes and NHERF1 Impact on Prognosis of Breast Cancer Patients.

Background: Breast cancer (BC) is a heterogeneous disease, and patients with apparently similar clinicopathological characteristics in clinical practice show different outcome. This study evaluated in primary BCs and in the subgroup of the triple-negative breast cancers (TNBCs) the level of tumor infiltrating lymphocytes (TILs), Na/H exchanger regulatory factor 1 (NHERF1) expression, and their association respect to the clinical outcome of patients.

Material And Methods: NHERF1 expression was assessed by immunohistochemistry in 338 BC samples; the analysis of TILs was examined using hematoxylin and eosin stained slides, according to International TILs Working Group 2014.

Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients.

Background: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stromal "s" and intratumoral "i" CD4+ and CD8+) in BC patients, focusing on the association between these markers and immunocheckpoint molecules such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death ligand 1 (PD-L1) and its receptor (PD-1).

Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced Non-Small Cell Lung Cancer (NSCLC): a Brief Report of 7 Cases.

Background: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark in the targeted therapy of non-small cell lung cancer (NSCLC). Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK protein expression, possibly an alternative to fluorescence in situ hybridization (FISH). In this study, the concordance of FISH and IHC to determine ALK status was evaluated, particularly focusing on discordant cases.

NHERF1 together with PARP1 and BRCA1 expression as a new potential biomarker to stratify breast cancer patients.

It has been recognized that Na/H Exchanger Regulatory Factor 1 (NHERF1) in breast cancer (BC) acts as a tumor suppressor or as an oncogenic protein, depending on its subcellular localization. This study aims to correlate NHERF1 expression to BRCA1 and PARP1 proteins, to investigate their relationship, and their biological and clinical significance. Using immunohistochemistry on tissue microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308 BCs including a subgroup (n=80) of triple negative BCs (TNBCs).

VEGF and TWIST1 in a 16-biomarker immunoprofile useful for prognosis of breast cancer patients.

This study concerns the expression of biomarkers involved in diverse pathways, such as progression, DNA repair mechanisms and angiogenesis to establish an immunoprofile capable of characterizing sporadic versus familial breast cancers (BCs). The aim was to identify a patient subgroup with a different clinical outcome, which could then be directed towards new targeted therapies. Hierarchical cluster analysis (HCA) was carried out using the immunohistochemical score from tissue microarray sections of an initial cohort of 183 (88 sporadic and 95 familial) patients with invasive BC.

Thyroglobulin Determination in Fine Needle Aspiration Biopsy Washout of Suspicious Lymph Nodes in Thyroid Carcinoma Follow up.

Background: Differentiated thyroid carcinomas (DTCs) account for about 1% of all human malignancies. Cervical lymph nodes metastases and recurrences in the thyroid bed frequently occur. Furthermore, about 10-15% of patients develop distant metastases.

Is immunohistochemistry of BRAF V600E useful as a screening tool and during progression disease of melanoma patients?

Background: In clinical practice the gold standard method to assess BRAF status in patients with metastatic melanoma is based on molecular assays. Recently, a mutation-specific monoclonal antibody (VE1), which detects the BRAF V600E mutated protein, has been developed. With this study we aimed to confirm the clinical value of the VE1 Ventana® antibody, as today a univocal validated and accredited immunohistochemical procedure does not exist, to preliminary detect BRAF status in our routine diagnostic procedures.

β-catenin interaction with NHERF1 and RASSF1A methylation in metastatic colorectal cancer patients.

There is an increasing need to identify new biomarkers in colorectal cancer (CRC) to further characterize this malignancy. β-catenin plays a central role in the Wnt signaling pathway. It also binds Na+/H+ exchanger regulating factor 1 (NHERF1) and interacts with the RAS-association domain family 1, isoform A (RASSF1A), but the mechanisms of this possible crosstalk are still not fully understood.

Immunoprofile from tissue microarrays to stratify familial breast cancer patients.

Familial breast cancer (BC) is a heterogeneous disease with variable prognosis. The identification of an immunoprofile is important to predict tumor behavior for the routine clinical management of familial BC patients. Using immunohistochemistry on tissue microarrays, we studied 95 familial BCs in order to analyze the expression of some biomarkers involved in different pathways.

Fine Needle Aspiration Cytology: A Tool to Study NHERF1 Expression as a Potential Marker of Aggressiveness in Lung Cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide and cytology is often the only diagnostic approach. Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) is a protein implicated in various cancers. However, the function of NHERF1 in lung cancer has not been described.

A new germline stop codon mutation in exon 15 of the APC gene predisposing to familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder related to germline mutations of the adenomatous polyposis coli (APC) gene. It is characterized by the detection of numerous adenomatous polyps that, if untreated, develop into colorectal cancer. We studied an Italian family with FAP history and the related colorectal tumor sample of the proband.

Prognostic significance of MGMT gene promoter methylation in differently treated metastatic melanomas.

Aims: The methylation status of the MGMT gene promoter, considered of prognostic significance by enhancing chemosensitivity to alkylating drugs in gliomas and melanomas, was evaluated in a series of primary melanomas and metastases of patients treated with different therapies, to identify any correlation with the patients' outcome or response to different therapeutic regimens.

Methods: Twenty-nine primary melanomas and 74 metastases, collected from 52 patients, were assessed for MGMT gene promoter methylation using a standard methylation specific PCR-based method. All materials were formalin fixed and paraffin embedded.

Well-differentiated papillary mesothelioma of the epididymis in a man with recurrent haematospermia.

We present a case of well-differentiated papillary mesothelioma of the epididymis occurring in a 60-year-old man who came to urologic consult after recurrent episodes of haematospermia. The patient denied pain, fever and trauma in genitals. Local examination revealed indolent swelling at the right testicle and ecography localised a well-circumscribed nodule at the epididymis tail, measuring 2 cm in greater diameter, with associated haemorrhagic hydrocele.

Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.

Background: To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT.

Materials And Methods: Immunohistochemical expression of c-KIT/CD117, p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs. Immunohistochemical and molecular data were statistically crossed with clinicopathological features.

Alterations of 9p21 analysed by FISH and MLPA distinguish atypical spitzoid melanocytic tumours from conventional Spitz's nevi but do not predict their biological behaviour.

Aim:   The aim of this study was to investigate whether 9p21 status influence the prognosis of the spitzoid melanocytic tumours, peculiar lesions whose biological behaviour cannot be predicted by histopathological criteria alone.

Methods And Results:   Twenty-eight atypical spitzoid tumours, 12 conventional Spitz's nevi and one congenital Spitz's nevus were studied by fluorescent in-situ hybridization (FISH) and multiple ligation-dependent probe amplification (MLPA) for the presence of 9p21 deletion. The 28 patients were aged 3-56years (mean 32, median 35), and follow-up ranged between 4 and 156months (mean 51, median 48).

EGFR polysomy in squamous cell carcinoma of the thyroid. Report of two cases and review of the literature.

Aims And Background: Primary squamous cell carcinoma of the thyroid gland (PSCCT) is an uncommon malignancy characterized by a poor prognosis. A radical surgical approach combined with radiotherapy or chemotherapy is the generally accepted treatment for this tumor. The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor modulating the cell proliferation and biological progression of many human epithelial tumors.

Giant genital cavernous haemangioma: case description and surgical management.

Giant genital haemangiomas are rare occurrences. Once properly diagnosed, they should be managed by surgery with wide and deep margins. We present a clinical case and provide suggestions for diagnosis and treatment of this unusual pathology.

Rapidly-growing hemangioma of the testicle clinically simulating an aggressive neoplasm. A case report.

We present a case of intraparenchymatous capillary-type hemangioma of the testicle in an adult. The patient was a 37-year-old man who showed a rapidly enlarging and palpable mass in left testicle. Radical orchiectomy was performed, and histological examination revealed an unencapsulated lobulated tumour with wide hemorrhagic portions.

Expression of estrogen receptor in hemangioma of the uterine cervix: reports of three cases and review of the literature.

The occurrence of hemangioma in the female genital tract, particularly in uterine cervix, is rare. The majority of them show asymptomatic behavior. Surgical excision remains curative in most of the cases.