Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Caracterización genética de cuatro poblaciones de ovinos criollos de Argentina / Genetic characterization of four populations of Argentinian creole sheep

Los ovinos criollos son los fundadores de la ganadería ovina en la Argentina y han contribuido de manera sostenida al desarrollo económico, social y cultural de algunas regiones del país. A pesar de ello, es un recurso zoogenético escasamente valorizado y por ende poco estudiado. En orden de caracterizar genéticamente a los ovinos criollos argentinos, se tomaron muestras de ADN de cuatro poblaciones representativas localizadas en las provincias de Buenos Aires, Corrientes, Santiago del Estero y Salta. Estas majadas se seleccionaron por ser grupos conservados, que presentan las características fenotípicas de la raza y no registran la introducción de animales de otras razas en el sistema de reproducción. Un total de 30 marcadores microsatélites y la región D-loop del ADN mitocondrial fueron analizados. El análisis de los microsatélites permitió evidenciar una alta diversidad genética intrapoblacional (Ho= 0,676; He= 0,685; PIC= 0,713). Dicha variabilidad es explicada por diferencias entre los patrones moleculares de los individuos estudiados que pueden clasificarse en 3 grupos de poblaciones significativamente diferentes: BA, SA, SE+CO. Dado que dichas poblaciones explican muy poco de la variabilidad total (7,6%), ellas deberían considerarse perteneciente a una misma raza. El análisis del D-loop mitocondrial demostró que los individuos analizados están relacionados con el haplogrupo asiático, el cual está ampliamente distribuido en las razas españolas que son las antecesoras de la raza criolla argentina. Los resultados obtenidos en este trabajo proveerán información para establecer criterios de manejo de este recurso genético de Argentina con el fin de implementar planes de conservación, recuperación y/o mejora de los programas.

Creole sheep are the founders of sheep farming in Argentina and have contributed in a sustained way to the economic, social and cultural development of some regions of this country. However, it is a scarcely valorised and poorly studied genetic resource. In order to genetically characterize the Argentinian Creole sheep, DNA samples were taken from four representative populations located in the provinces of Buenos Aires, Corrientes, Santiago del Estero and Salta. These flocks were selected because they are considered to be conserved groups, they have the phenotypic characteristics of the creole breed and there are no records about the introduction of animals of other breeds into those systems. A total of 30 microsatellites and the D-loop region of mitochondrial DNA were analysed. Microsatellite analysis showed high level of genetic diversity within populations (Ho= 0.676; He= 0.685; PIC= 0.713). This variability is explained by differences between molecular patterns of the studied individuals, which can be classified into three significantly different population groups: BA, SA, SE+CO. Since these populations explain very little of the total variability (7.6%), it can be considered that they belong to a same race. The analysis of the mitochondrial D-loop showed that Argentinian Creole sheep have haplotypes belonging to the Asian haplogroup, which is widely distributed in the Spanish breeds, which are considered to be their ancestors. The results obtained in the present study will provide information to develop management criteria for this genetic resource in Argentina, in order to implement their conservation, recovery and/or to develop breeding programs.

Gastrointestinal stromal tumor (GIST) presenting in a Meckel's diverticulum.

A meckel's diverticulum is a congenital abnormality of the GI tract seen in approximately 3% of the population. Tumor arising within this entity is a rare, although know complication. We report a gastrointestinal tumor arising within a Meckel's diverticulum in a 28-year-old male.

Cytologic findings in the differential diagnosis of C-cell hyperplasia and medullary carcinoma by fine needle aspiration. A case report.

BACKGROUND: The cytologic features of C-cell hyperplasia of the thyroid have not been previously addressed in the literature. We describe the first case, to our knowledge, of C-cell hyperplasia that was suggested by fine needle aspiration. CASE: Cellular material was obtained from a nonnodular region of the thyroid gland in a 67-year-old male with chronic diarrhea, unexplained elevated serum calcitonin, no clinically detectable thyroid mass and no known medical or family history of an endocrine disorder. Aspiration yielded a scant bimodal cell population composed of benign follicular cells and a second population of larger cells, later confirmed as C-cells via immunohistochemistry. Although the diagnosis of medullary carcinoma was entertained, the absence of a discrete mass clinically and the presence of two interspersed, distinct cell populations suggested the alternate diagnosis, C-cell hyperplasia, which was confirmed by subsequent thyroidectomy. CONCLUSION: C-cell hyperplasia can mimic medullary carcinoma biochemically, and this case suggests the possible role of fine needle aspiration of the thyroid to distinguish between the two. In patients with elevated serum calcitonin and absence of a discrete thyroid nodule, the finding of clusters of calcitonin-positive cells intermixed with normal follicular cells by fine needle aspiration may provide a means of making a presurgical diagnosis of C-cell hyperplasia.

Epithelioid cells in myoid hamartoma of the breast: a potential diagnostic pitfall for core biopsies.

OBJECTIVE: We report six cases of myoid hamartoma of the breast, a rare benign lesion in which the characteristic smooth muscle cells may have epithelioid histology. We emphasize the importance of radiographic correlation and immunohistochemical studies to diagnosis, particularly on stereotactic core biopsies, to avoid potential confusion with infiltrating lobular carcinoma. DESIGN: Case studies. Prospective and retrospective analysis of six cases, including stereotactic biopsy of two. SETTING: Academic medical center-based pathology practice. PATIENTS: Six postmenopausal women, aged 50 to 59 years, with palpable or nonpalpable mammographically evident breast masses. RESULTS: All the lesions were radiographically well circumscribed, most showing heterogeneous radiodensity. Histologically variable amounts of glandular, fibrous, and adipose tissue were admixed with smooth muscle cells, which occasionally had prominent epithelioid features. All the lesions' myoid cells stained for smooth muscle markers as well as steroid receptor proteins. Stereotactic core biopsy was diagnostic in one case, making excision unnecessary. CONCLUSIONS: With proper radiographic correlation and immunohistochemical confirmation, myoid hamartoma can be confidently diagnosed even on the limited tissue samples yielded by stereotactic core biopsy.

Intra-abdominal pulmonary sequestration exhibiting congenital cystic adenomatoid malformation. Report of a case and review of the literature.

We describe the fifth case, to our knowledge, of an intra-abdominal pulmonary sequestration that histologically displayed the features of congenital cystic adenomatoid malformation (CCAM) type 2. This mass was found during routine prenatal ultrasound in an infant with no other congenital malformations. A literature search found 13 previously reported cases of CCAM in extralobar pulmonary sequestration (EPS), nine of which were thoracic and only four were intra-abdominal. An analysis of our case and the 13 previously reported cases shows that the clinical features of EPS containing CCAM type 2 do not differ significantly from those of EPS occurring alone. The presence of CCAM type 2 in our patient is consistent with previously reported cases. Extralobar pulmonary sequestrations located in the abdomen are rarely diagnosed prior to excision, and the presence of CCAM type 2 in this situation may further compound diagnostic difficulties. The morphologic features separating CCAM into three distinct types and the exclusive association of CCAM type 2 occurring in EPS are also discussed.