Cancer Biomarkers - Volume 14, issue 2-3

Authors: Kontogeorgos, George

Article Type: Research Article

Abstract: Endocrine tumors were considered relatively infrequent neoplasms. However, during the last decades, their frequency gradually increased. The use of imaging techniques, guided FNA biopsy, an endoscope camera in the investigation of endocrine lesions, permits early diagnosis. At the histological level, new applications such as non-biotin containing immunohistochemical detection systems, tyramide amplification method, in situ hybridization, FISH, CGH, and other molecular techniques have provided better knowledge on the protein and molecular background. The investigation of somatostatin and dopamine receptors assists targeted therapy of endocrine tumors. Novel treatment modalities have emerged for the management of pituitary and gastroenteropancreatic tumors respectively. Despite this …progress, in some instances, the morphological diagnosis remains questionable. Similarities among normal elements, hyperplastic conditions and benign or malignant lesions can make separation difficult. The “gray zones” representing the overlapping in the sequence of normal parenchyma/ hyperplasia/ adenoma/ carcinoma signify a difficult and controversial diagnostic task, which merits special attention. Furthermore, in most endocrine tumors, the diagnosis of carcinoma is justified only in the presence of local or distant metastases. More precise guidelines are needed, by improving the currently available criteria, to minimize the “gray zones”, leading to a more accurate separation of such endocrine lesions. Show more

Keywords: Classification, endocrine, imaging, pathology, therapy

DOI: 10.3233/CBM-130353

Citation: Cancer Biomarkers, vol. 14, no. 2-3, pp. 163-167, 2014

Authors: Caponio, Maria Angela | Addati, Teresa | Popescu, Ondina | Petroni, Stella | Rubini, Vincenza | Centrone, Marilena | Trojano, Giuseppe | Simone, Giovanni

Article Type: Research Article

Abstract: Determining the primary site of uterine adenocarcinoma (ADC) may be problematic, especially with small specimens. This is particularly important in light of the increase of endocervical and endometrial adenocarcinoma and the decrease in incidence of squamous cell carcinoma. P16INK4a , a member of the INK4 family of cell cycle regulatory proteins, plays a critical role. It functions as a negative regulator of cell cycle progression and differentiation by controlling the activity of the tumor-suppressor protein retinoblastoma (pRb), which regulates the cell cycle. Its expression is variable according to the tumoral histotype and in metastasis. The aim …of this study was to investigate p16INK4a expression in endocervical, endometrial, and metastatic ADCs of extra-uterine origin. Fifty gynaecological biopsies (cervix or endometrium) comprised the study for p16INK4a determination. Cases were classified as (1) diffuse positive (P), in intense nuclear immunostaining and/or cytoplasmic in > 30% of neoplastic cells; (2) focal positive (FP), in intense immunostaining in 10% to 30% in isolated cells or small groups; and (3) negative (N), in absence of immunostaining or weak, sporadic immunostaining in < 10% of neoplastic cells. Included in the study were the following: 6 endocervical ADCs, 11 endometrioid-type endometrial ADCs, 5 endometrial serous papillary ADCs, 7 ovarian ADCs, 4 large intestine ADCs, 1 breast ADC, 12 not-otherwise-specified (NOS) ADCs, and 4 endocervical biopsy without atypia (as control). Diffuse, strong positivity with p16INK4a suggests an endocervical rather than an endometrial or metastatic ADC. In fact, a p16INK4a positive immunostaining pattern was prevalent in endocervical (83%) and serous papillary ADCs of endometrial or ovarian origin, whereas endometrioid ADCs such as metastatic non-ovarian lesions generally presented only focal or negative immunostaining. 10/12 cases of ADC-NOS were reclassified using p16INK4a immunostaining: 2 as endocervical ADCs (2 P), 4 as endometrioid-type endometrial ADCs (2 FP, 2 N), 3 as endometrial serous papillary ADCs (3 FP), and 1 as ovarian serous papillary ADC (1 FP). Show more

Keywords: Uterine adenocarcinoma, metastatic ADCs, NOS-ADCs, immumunohistochemistry, p16INK4a

DOI: 10.3233/CBM-130326

Citation: Cancer Biomarkers, vol. 14, no. 2-3, pp. 169-175, 2014

Authors: Saponaro, Concetta | Malfettone, Andrea | Dell'Endice, Teresa Stefania | Brunetti, Anna Elisabetta | Achimas-Cadariu, Patriciu | Paradiso, Angelo | Mangia, Anita

Article Type: Research Article

Abstract: NHERF1 (Na+ /H+ exchanger regulatory factor) is a scaffolding protein, consists of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region. NHERF1 recruits macromolecular complexes at the apical membrane of epithelial cells in many epithelial tissues. It is involved in trafficking and regulation of transmembrane ion transporters and G protein-coupled receptors. Further, NHERF1 also linked other molecules involved in cell growth and cancer progression, such as PDGFR, PTEN, β-catenin, EGFR and HER2/neu. In this review, we focus on the role of NHERF1 during cancer development. Evidences of its involvement in cancer development are present in hepatocellular carcinoma, schwannoma, …glioblastoma, colorectal cancer and particularly in breast cancer. Recent findings obtained from our laboratory show that cytoplasmic NHERF1 expression increases gradually in breast cancer during carcinogenesis, and its overexpression is associated with aggressive clinical parameters, unfavourable prognosis, and increased tumor hypoxia. Interestingly, also nuclear NHERF1 expression seems to play a role both in carcinogenesis and progression of colorectal cancer. These data suggest that NHERF1 could be a new biomarker of advanced malignancies. Show more

Keywords: NHERF1, cancers, carcinogenesis, cancer progression

DOI: 10.3233/CBM-130329

Citation: Cancer Biomarkers, vol. 14, no. 2-3, pp. 177-184, 2014

Authors: Chiorean, Roxana | Braicu, Cornelia | Florian, Ioan Stefan | Leucuta, Daniel | Montefrancesco, Chiara | Crisan, Doinita | Berindan-Neagoe, Ioana | Cernea, Valentin

Article Type: Research Article

Abstract: Glioblastoma multiforme (GBM) represents a very aggressive brain tumor. Angiogenesis is the formation of a network of new blood vessels, from preexisting ones. It plays an important role in the formation of the tumor, as it supplies it with oxygen and nutrients. Angiogenesis and inflammation play essential roles in glioblastoma development. These processes are regulated by the balance of a few molecules, acting as pro- or antiangiogenic and pro- or anti-inflammatory factors. The purpose of our study was to evaluate the expression of 7 markers involved in angiogenesis and inflammation pathways in patients with glioblastoma. VEGF, PDGF-bb, IGF-1, TGF-β, TNF-α, …IL-6 and IL-8 levels were measured using the ELISA method, in the preoperative sera of 14 patients with histopathologically confirmed glioblastoma multiforme and 32 healthy patients. Serum levels of PDGF-bb, IGF-1 and IL-8 were significantly higher in patients with GBM, compared to the control group (p-value < 0.01). A statistically significant correlation has been found between IGF-1 and IL-6 levels (rho= −0.53, p-value < 0.05) and also between TNF-α and IL-6 levels (rho=0.60, p-value < 0.05). Statistically significant associations have been found between the presence of low levels of IL-8 and the development of coagulation necrosis (p-value < 0.05), high levels of VEGF and development of ischemic necrosis (p-value < 0.01) and high levels of IL-8 and the development of endothelial hyperplasia (p-value < 0.05). We have observed no statistically significant associations between the serum levels of the markers and the survival rates. Show more

Keywords: Glioblastoma multiforme, angiogenesis, inflammation, ELISA, histopathology, survival rates

DOI: 10.3233/CBM-130310

Citation: Cancer Biomarkers, vol. 14, no. 2-3, pp. 185-194, 2014

Authors: Sergio, Roman-Roman

Article Type: Other

DOI: 10.3233/CBM-130339

Citation: Cancer Biomarkers, vol. 14, no. 2-3, pp. 195-196, 2014