Biomedical subjects

Helen E Remotti

Publications and source records attributed to Helen E Remotti.

5 recordsLinked to original sources

PubMed2006

BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas.

The Raf/MEK/ERK (MAPK) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Our study was performed to elucidate a possible role of BRAF in the development of IPMN (Intraductal Papillary Mucinous Neoplasm) and IPMC (Intraductal Papillary Mucinous Carcinoma) of the pancreas. Mutations of BRAF and KRAS were evaluated in 36 IPMN/IPMC samples and two mucinous cystadenomas by direct genomic sequencing. Exons 1 for KRAS, and 5, 11, and 15 for BRAF were examined. Totally we identified 17 (47%) KRAS mutations in exon 1, codon 12 and one missense mutation (2.7%) within exon 15 of BRAF. The mutations appear to be somatic since the same alterations were not detected in the corresponding normal tissues. Our data provide evidence that oncogenic properties of BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.

Adenocarcinoma, Mucinous↗

PubMed2006

PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas.

PURPOSE: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene in various human solid tumors. More than 75% of those somatic mutations are clustered in the helical (exon 9) and kinase domains (exon 20). The three hot-spot mutations, E542K, E545K, and H1047R, have been proven to elevate the lipid kinase activity of PIK3CA and activate the Akt signaling pathway. The mutational status of PIK3CA in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) has not been evaluated previously. EXPERIMENTAL DESIGN: To evaluate a possible role for PIK3CA in the tumorigenesis of IPMN and IPMC, exons 1, 4, 5, 6, 7, 9, 12, 18, and 20 were analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing. RESULTS: We identified four missense mutations in the nine screened exons of PIK3CA from 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported as a hot-spot mutation. The remaining three mutations, T324I, W551G, and S1015F, were novel and somatic. CONCLUSION: This is the first report of PIK3CA mutation in pancreatic cancer. Our data provide evidence that the oncogenic properties of PIK3CA contribute to the tumorigenesis of IPMN/IPMC.

Adult↗

PubMed2003

Anorectal gastrointestinal stromal tumors: CT and MR imaging features with clinical and pathologic correlation.

OBJECTIVE: The purpose of this study was to describe the imaging features of anorectal gastrointestinal stromal tumors with clinical and pathologic correlation. CONCLUSION: Anorectal gastrointestinal stromal tumors are mesenchymal neoplasms that typically arise in the muscularis propria of the intestinal wall. The cross-sectional imaging appearance is that of a well-defined mural mass that may have an exophytic component and may invade adjacent structures. A prominent intraluminal component is a rare feature.

Aged↗

PubMed2002

Expression of KIT (CD117) in angiomyolipoma.

Angiomyolipoma is a unique mesenchymal tumor postulated to arise from perivascular epithelioid cells. Immunohistochemical studies have shown that angiomyolipomas express the melanocytic markers HMB-45, MART-1 (Melan A), microphthalmia transcription factor, and tyrosinase, in addition to smooth muscle actin. KIT (CD117) is a transmembrane growth factor receptor expressed in cells of melanocytic and a variety of other cell lineages. To date, KIT immunoreactivity has not been systematically studied in angiomyolipoma. In this study we immunohistochemically analyzed a series of 21 angiomyolipomas (15 hepatic, six renal) with KIT. All were KIT positive: 14 of 21 (67%) with 3+ staining (>50% of tumor cells), 4 of 21 (19%) with 2+ staining (25-50% of tumor cells), and 3 of 21 (14%) with 1+ staining (<25% of tumor cells). In comparison, the percent of angiomyolipomas showing 3+ staining with HMB-45 was 62% and with Melan A was 52%. Positive KIT staining was detected in the epithelioid, spindle, and intermediate small round cells. Most cases showed diffuse cytoplasmic positivity. Strong perinuclear staining was present in the vacuolated clear epithelioid cells. There was focal KIT staining of fat cells. KIT was not detected in the endothelial cells lining blood vessels within the tumor. KIT may be a useful ancillary marker for the diagnosis of angiomyolipoma. Angiomyolipoma should be included in the differential diagnosis of KIT-positive tumors.

Angiomyolipoma↗

PubMedDate not supplied

Gastrointestinal stromal tumors: radiologic features with pathologic correlation.

Gastrointestinal stromal tumors (GISTs) are unique neoplasms that occur throughout the gastrointestinal tract, mesentery, omentum, and retroperitoneum. They are the most common mesenchymal neoplasm of the gastrointestinal tract and are defined by their expression of KIT (CD117), a tyrosine kinase growth factor receptor. The expression of KIT is important to distinguish GISTs from other mesenchymal neoplasms such as leiomyomas, leiomyosarcomas, schwannomas, and neurofibromas and to determine the appropriateness of KIT-inhibitor therapy. The series described herein was accumulated over 2 years and includes 64 pathologically proved GISTs (28 gastric, 27 small intestinal, six anorectal, one colonic, one esophageal, and one from the small bowel mesentery). Radiologic features of GISTs vary depending on tumor size and organ of origin. Since most GISTs arise within the muscularis propria of the stomach or intestinal wall, they most commonly have an exophytic growth pattern and manifest as dominant masses outside the organ of origin. Dominant intramural and intraluminal masses are less common radiologic manifestations. GISTs occurring in the gastrointestinal tract and mesentery characteristically have hemorrhage, necrosis, or cyst formation that appears as focal areas of low attenuation on computed tomographic images. Although the radiologic features of GISTs are often distinct from those of epithelial tumors, criteria to separate GISTs radiologically from other nonepithelial tumors have not yet been fully developed.

Diagnosis, Differential↗