Rol patogénico del gen supresor de tumores PTEN en cáncer ovárico asociado a endometriosis / Pathogenic role of PTEN tumor suppressor gene in ovarian cancer associated to endometriosis

Background: Endometrioid carcinoma and clear cell carcinoma of the ovary are associated to endometriosis. Somatic mutations of PTEN (10q23.3) are present in endometrial endometrioid carcinoma. Therefore, these mutations could be also present in ovarian tumors. Molecular studies show that solitary endometriotic cysts are monoclonal, have aneuploid DNA, have a loss of 9p,11q and 22q heterozygosity (LOH) and a higher cellular proliferation index of the epithelial component. Aim: To determine the cellular proliferation index using Ki 67, the immunohistochemical expression of PTEN and LOH in patients with ovarian endometriosis without atypia (EN), ovarian endometriosis with atypia (EA) and endometriosis with adjacent ovarian carcinoma (ET). Material and methods: Paraffin embedded samples of 37 endometrioid and clear cell carcinomas of the ovary (CC/CE), 15 solitary ovarian EN and 15 ovarian EA, were studied. Expression of Ki 67 and PTEN was measured by immunohistochemistry. LOH of 10q23.3 locus was measured by polymerase chain reaction. Results: Ki 67 was 5.5 and 2.3% in EA and EN, respectively (p <0.005). There was a histological correlation between EA and a higher cellular proliferation index. PTEN was negative in 5 of 15 EN, 9 of 15 EA and 30 of 37 CE/CC. There was a correlation between LOH and loss of PTEN protein in EN, EA and ET (60%). Conclusions: Negative expression on PTEN in EN; EA; ET and CE/CC is a manifestation of the inactivation of this gene. The mechanisms that cause this inactivation, must be elucidated.

Diagrama de flujo inmunohistoquímico para la diferenciación entre adenocarcinomas primarios y tumores metastásicos extraginecológicos más frecuente en el ovario / Immunohistochemical flow chart to differentiate between primary adenocarcinomas and the most frequent extragynecological metastases in the ovary

Background: The pathological differential diagnosis between primary and metastatic ovarian malignant tumors is usually difficult, specially for tumors originating in the gastrointestinal system or breast. Aim: To define an immunohistochemical flow chart to discriminate these tumor types. Material and methods: We performed a immunostaining analysis using a panel of six antibodies (CK 7, CA 125, CEA, CK20, BRST-2 and CA 15-3) in 3 tumor groups: 11 ovarian, 14 breast and 12 colonic primary tumors and in a study group of 38 ovarian tumors whose primary origin was unknown. Results: We defined an ovarian immunohistochemical pattern (CEA-/CK20-, 45 percent in ovarian tumors, 0 percent in breast or colonic tumors, p <0.001); an ovary/breast pattern (CEA+/CK20-, 0 percent in colonic tumors, p <0.001): a breast pattern (CEA+/CK20-/BKST-2+, 64 percent in breast tumors and 0 percent in colonic and ovarian tumors, p <0.001) and a colonic pattern (CEA+/ CK20+/CK7-, 67 percent in colonic tumors and 0 percent in breast and ovarian tumors, p <0.001). Conclusions: Employing a simple panel of antibodies, characteristic immunohistochemical patterns were defined for ovarian, breast and colonic tumors. These patterns allowed the identification of the origin of most tumors of the study group

Prevalencia de anticuerpos anti islotes pancreáticos en 1.021 parientes de diabéticos tipo 1 / Prevalence of anti pancreatic islet antibodies among 1.021 relatives of type 1 diabetic patients

Background: An immunological damage of beta cells in the islets of Langerhans, plays a role in the pathogenesis of type 1 diabetes. Recently, the identification of individuals in pre clinical phase and with high risk of developing type 1 diabetes, has become possible by means of the detection of immune markers such as islet cell antibodies (ICA) and the measurement of first phase response of insulin (FPRI). Subjects and methods: We studied 1,021 first degree relatives of type 1 diabetics, aged 4 to 35 years. ICA were measured using poly-IgG peroxidase in sections of human pancreas. In those subjects with positive ICA and normal oral glucose tolerance test, the FPRI was measured. FPRI was defined as the sum of insulinemias at minutes 1 and 3 after a three minutes 0.5 g/kg glucose load. Results: Thirty subjects were ICA (+), defined as having more than 20 juvenile diabetes foundation units (prevalence of 2.9 percent). No differences in age, sex and closeness of familial relationship was found between ICA (+) and ICA (-) individuals. FPRI was measured in 24 subjects with normal oral glucose tolerance test and was normal in five. Seventeen subjects had a decreased response (between percentiles 1 and 5) and two had a response below percentile 1. No relationship between ICA levels and FPRI was found. Conclusions: The early detection of populations at risk of developing type 1 diabetes should be regarded as an important tool to better understand the natural history of the disease and to develop preventive programs in the future

Marcadores tumorales inmunohistoquímicos en carcinoma ductal infiltrante de la mama / Immunohistochemical tumoral markers in infiltrating ductal mammary carcinoma

Background: Immunohistochemical techniques allow the study of tumoral markers with predictive or prognostic value. Aim: To study tumoral markers in mammary carcinoma and to relate these markers with age and tumoral histological grade. Material and methods: The expression of nuclear estrogen receptor (RE), nuclear progesterone receptor (PGR), p53 and c-erb-B2 proteins was analyzed in 382 cases of infiltrating ductal carcinoma of the breast. Results: The histological grade was I in 22 percent tumors, II in 56 percent and III in 23 percent. Forty nine percent of tumors had positive staining for RE, 41 percent for RPG, 45 percent for p53 and 57 percent for c-erb-B2. Correlation was found between histological grade and expression of RE, p53 and c-erb-B2 between RE and PGR, RE and c-erb-B2 and between c-erb-B2 and p53. RE expression correlated with age. Conclusions: A reliable and rapid evaluation of these markers can be achieved using immunohistochemical staining. The present results are similar to other biochemical and immunohistochemical studies

Análisis histopatológico semicuantitativo de la gastritis crónica: índice de extensión y grado / Histopathological semiquantitative analysis of chronic gastritis: extension and grade index

Three endoscopic systematic biopsies were obtained from 261 patients showing chronic gastritis. Histopathologic features of chronic gastritis were graded from 0 to 3 points according to the Sydney System. In addition, an extension and grading histopathologic score was applied. This score was obtained from the sum of qualified grades for each feature in all three samples. Inflammation, activity, atrophy and intestinal metaplasia were predominantly grade 1 and H pylori density was predominantly grade 2. Only 2,6 percent of the sections whith out atrophy showed intestinal metaplasia, while 79,3 percent of the sections depicting grade 2-3 intestinal metaplasia showed moderate to severe atrophy. Inflammation was more severe in antral lesser curvature and the more severe atrophy was present in the antrum than in the corpus mucosa. Sydney System and extension and grading histopathologic score showed more extensive activity in patients older than 45 years. A lower histopathologic score of H pylori was seen in these patients. The presence of H pylori was directly correlated with inflammation severity and inversely with atrophy. These results, in accordance with data shown in the literature, suggest that the Sydney System and extension and grading histopathologic score can be applied to compare chronic gastritis features in different groups of patients

Cáncer de mama: comparación entre la determinación bioquímica e inmunohistoquímica de los receptores de estrógenos / Breast cancer: comparison between biochemical and immunohistochemical determination of estrogen receptors

Immunohistochemical (IH) assessment of nuclear estrogen receptor has been considered an alternative method to conventional biochemical assay. The present work intends to compare specificity and sensitivity of IH and biochemical technique to assess nuclear estrogen receptor in formalin-fixed and paraffin-embedded mammary carcinoma samples. IH positive reaction was defined as 14 percent or more nuclear staining in 100 cells counted under high magnification (400x). Biochemical assay was considered positive over 10 fmol/mg of protein. 66 cases were collected with a mean age of 55.6 years and a mean tumor size of 25.2 mm. Histologically, 62 cases were ductal carcinomas, 2 lobular carcinomas and 2 medullary carcinomas. Biochemical assay for estrogen receptor was positive in 35 cases (63 percent) and IH in 40 cases (71 percent). The present results show that IH assessment of estrogen receptor is highly specific and sensitive. Estrogen receptor present in non-tumor cells and blood vessels walls may disclose false positive biochemical results and false negative result if the tumor mass is small or there are isolated tumor cells. IH assessment of estrogen receptor can be performed in small samples, including in situ lesions. The method is fast, reliable and of lower cost. IH may be considered the method of choice in cases with insufficient samples for biochemical assay and/or tumors containing scant cells

Marcadores inmunológicos y de secreción insulínica en pacientes diabéticos no insulino dependientes con fracaso secundario a drogas hipoglicemiantes orales / Immunologic and insulin secretion markers in diabetic non insulin dependent patients with secondary failure to oral hypoglycemic agents

The pathogenesis of secondary failure to hypoglycemic agents is heterogenous. Some patients are true insulin dependent diabetics with a slow autoimmune disease suggested by their positive islet cell antibodies. Others, have an increased insulin resistance. To assess the frequency of positive islet cell antibodies in diabetic patients with secondary failure to oral hypoglycemic agents. 31 diabetics, 16 with recent (less than six months) secondary failure and 15 with metabolically stable non insulin dependent diabetes were studied. All patients were older than 25 years old and had a body mass index of less than 30 kg/m2. C peptide levels before and at 5,15 and 30 min after IV glucagon, islet cell antibodies using the Poly Human IgG peroxidase method an insulin sensitivity and secretion (estimated by the Homeostasis Model Assessment) were measured. Patients with secondary failure had lower C peptide levels compared to subjects with stable diabetes (basal: 1.5ñ0.2 and 2.8ñ0.2 ng/ml; 5 min: 2.4ñ0.3 and 5.5ñ0.5 ng/ml; 15 min:1.9ñ0.3 and 4.0ñ0.6 ng/ml; 30 min:1.6ñ0.3 and 3.4ñ0.5 ng/ml). Beta cell activity was 20.6ñ4.3 percent in patients with secondary failure and 92.2ñ9 percent in stable diabetics (p<0.01). Insulin sensitivity was similar in both groups (48.6ñ6 and 42.8ñ3.5 percent respectively). Three patients with secondary failure and none with stable diabetes had positive islet cell antibodies. When comparing patients with secondary failure and positive antibodies and subjects with secondary failure and negative antibodies, the former had non significantly lower age, BMI and C peptide levels. Some diabetic patients with secondary failure have positive islet cell antibodies. They should be measured in these patients to start insulin treatment precociously

Expresión inmunohistoquímica de la oncoproteína p53 en neoplasias melanocíticas de la piel / Immunohistochemical expression of p53 oncoprotein in melanocytic neoplasms of the skin

Con objeto de caracterizar la expresión inmunohistoquímica de la oncoproteína p53 en neoplasias melanocíticas de la piel, se estudiaron 100 casos de nevos y melanoma maligno primario de la piel del período enero 1990 agosto 1994. Se recolectaron 68 casos de nevo melanocítico y 32 casos de melanoma maligno. Reacción positiva se encontró en 8 nevos melanocíticos (11,8 por ciento) y 17 melanomas (53,1 por ciento). Del total de nevos, reacción positiva se observó en 1 compuesto, 2 nevos dérmicos, 3 nevos de Clark y 2 nevos de Spitz. La reacción positiva en melanoma maligno varió de 33 a 71 por ciento en las distintas variedades de melanoma. Los resultados muestran una expresión de oncoproteína p53 de aproximadamente 53 por ciento en melanoma maligno y 12 por ciento en nevos melanocíticos. La reacción positiva se observó en menos del 5 por ciento de las células. La expresión de oncoproteína p53 no está limitada a neoplasias melanocíticas malignas y las mutaciones del gen p53 parecen acumularse en la fase de progresión del melanoma maligno de la piel