[Predictive value of intraepithelial (CD3) T-lymphocyte infiltration in resected colorectal cancer]. / Valor predictivo de la infiltración por linfocitos T intraepiteliales (CD3) en el pronóstico del cáncer colorrectal resecado.

INTRODUCTION: Colorectal cancer (CRC) can induce an anti-tumoral immune response mediated by T-lymphocytes, which express CD3. OBJECTIVES: To analyze the prognostic value of tissue expression of intraepithelial CD3 (CD3I) both overall and in the early tumoral stages. METHODS: We revised 251 patients with resected CRC and favorable clinical course. CD3I expression was analyzed by immunohistochemistry. Multivariate analysis was used to analyze the variables independently associated with survival. We analyzed CD3I(+) expression in relation to survival and tumoral progression, both overall and in patients with pTNM(I-II) stage tumors. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CD3I expression were analyzed. RESULTS: A total of 25.9% of patients with CRC were CD3I(+). After a mean follow-up of 74 months, CD3I(+) expression showed a favorable prognostic value for survival in the multivariate analysis (p=0.045). Survival curves and absence of tumoral progression were more favorable in CD3I(+) cases, both overall (p=0.009 and p=0.004, respectively), and in stages I-II (p=0.029 and p=0.015). The specificity and positive predictive value of CD3I(+) were as follows: Survival: overall: specificity =0.89; positive predictive value =0.91. Stage (I-II): specificity =0.94; positive predictive value =0.98. Absence of tumoral progression: overall: specificity=0.89; positive predictive value =0.88. Stage (I-II): specificity =0.92; positive predictive value =0.96. CONCLUSIONS: CD3I expression has an favorable independent prognostic value, with statistically significantly higher percentages of survival and absence of tumoral progression. This more favorable outcome is maintained in the less advanced stages (I-II). CD3I expression shows high specificity and positive predictive value.

Drawing up an individual risk index for development of metachronous neoplastic lesions in resected colorectal cancer.

AIM: to identify possible risk factors for the development of metachronous lesions in colorectal cancer (CRC) which would allow to establish a post-surgical individual prognostic index. PATIENTS AND METHODS: three hundred eighty-two surgically treated CRC were reviewed. We compared the incidence of metachronous lesions in 40 variables concerning patient clinical data and initial neoplastic findings. An individual risk index for metachronicity was drawn up including those variables which presented significant differences in multivariate logistic regression, dividing patients into three groups. RESULTS: variables with prognostic value for metachronicity were distal cancer location: OR = 2.30 (1.03-5.13), alcohol intake: OR = 2.20 (1.08-4.48), presence of synchronous adenomas: isolated: OR = 2.47 (1.03-4.48), multiple: OR = 4.26 (1.78-10.17), and presence of synchronous advanced adenoma: OR = 2.91 (1.52-12.60). Tumor MUC-5 expression proved to have a protective role: OR = 0.23 (0.08-0.66). An individual risk score was established considering these variables and patients could be classified into three groups, with a discrimination power for metachronicity of p < 0.0000001. Classification in high and low risk groups had a sensitivity = 75.32%, specificity = 84.21%, positive predictive value = 75.34%, negative predictive value = 92.31% and global diagnostic accuracy = 80.75%. CONCLUSIONS: the identification of risk factors for the development of metachronous lesions allow to calculate, at the time of surgical treatment, an individual prognostic index and to classify patients into three different risk groups. In high and low risk groups, both specificity and accuracy were acceptable for the prognosis of metachronous lesions, being remarkable the negative predictive power of our classification, which could become relevant when planning a different endoscopic follow up of these patients.

[Imported histoplasmosis in Navarra: presentation of four cases]. / Descripción de cuatro casos de histoplasmosis importada en Navarra.

OBJECTIVE: Histoplasmosis is a fungal infection caused by the dimorphic fungi Histoplasma capsulatum. Its incidence in Spain has increased in recent years, mainly due to the increased presence of immigrants from Latin America and increased travel to the continent for tourism and cooperation. Our aim was to review the clinical characteristics of cases of histoplasmosis diagnosed in our hospital during the last six years. CASE REPORTS: We diagnosed 4 cases from 4 patients from South America, 3 of whom were HIV positive and 1 diagnosed with dermatomyositis was treated with immunosuppressive drugs. The laboratory diagnosis was carried out by histological and microbiological study, by culture and specific PCR directly on the sample. DISCUSSION: As it is an imported infection there needs to be a high level of suspicion and a detailed history taken to get a diagnosis. This infection requires a differential diagnosis between febrile syndrome in immunosuppressed patients, both HIV positive and immunosuppressive therapy, which originate from endemic areas, or who have a history of staying in them.

[Primary adenocarcinoma of the seminal vesicles]. / Adenocarcinoma primario de vesículas seminales.

OBJECTIVES: To report one case of primary adenocarcinoma of the seminal vesicles. METHODS/RESULTS: We report the case of a 69-year-old man with obstructive voiding symptoms. Digital rectal examination reveals a marked enlargement of posterior area of the prostate and surrounding tissues. Transrectal needle biopsy shows a primary adenocarcinoma of the seminal vesicles. CONCLUSION: Primary adenocarcinoma of the seminal vesicles is an extremely uncommon neoplasm that is often difficult to diagnose as it has in specific morphology and can be confused with other primary adenocarcinomas from prostate, bladder or colon.

Differences and molecular immunohistochemical parameters in the subtypes of infiltrating ductal breast cancer.

Breast cancer is a heterogeneous disease, and patients are categorized into subtypes according to gene expression. We studied the associations among molecular, immunohistochemical, and clinicopathologic features and their distribution according to the subtypes luminal, HER2, basal, and normal-like in 60 patients with invasive ductal breast carcinoma without distant metastasis at the time of diagnosis (M0). We evaluated the hypermethylation of the CDH-1, RASSF1A, SIAH-1 and TSLC-1 genes by methylation-specific polymerase chain reaction and the expression of p53, bcl-2, cyclin D1, E-cadherin, and beta-catenin proteins in tissue microarrays by immunohistochemical analysis. Expression of bcl-2 was associated with the luminal subtype (P=.003), and CDH-1 hypermethylation was present preferentially in HER2 tumors (P=.038). The basal subtype was characterized by the expression of beta-catenin (P=.003). The hypermethylation of CDH-1 and the expression of bcl-2, cyclin D1, and beta-catenin proteins differ among breast cancer subtypes.

Hypermethylation, risk factors, clinical characteristics, and survival in 235 patients with laryngeal and hypopharyngeal cancers.

BACKGROUND: It has been established that promoter hypermethylation occurs in several genes during the pathogenesis of head and neck cancer. The authors investigated the role played by the hypermethylation of 4 cancer-related genes in the survival of patients who had laryngeal and hypopharyngeal cancer and in the occurrence of second primary tumors. METHODS: Archival paraffin-embedded tissue (PET) samples were available from patients who were enrolled in a multicentric European case-control study that was performed between 1979 and 1982 and was followed up to 2000. Genomic DNA extracted from 235 PET samples were analyzed for promoter methylation status of the p16, O(6)-methylguanine-DNA methyltransferase (MGMT), death-associated protein kinase (DAP-K), and E-cadherin genes by using a methylation-specific polymerase chain reaction assay. RESULTS: Hypermethylation was present in 44% of samples for p16, in 27% of samples for MGMT, in 42% of samples for DAP-K, and in 43% of samples for E-cadherin. Hypermethylation of either individual genes or their combination was not associated with mortality from all causes, mortality from upper aerodigestive tract cancer, or the occurrence of second primary tumors. CONCLUSIONS: The analysis of a large series of patients with laryngeal and hypopharyngeal cancer suggested that hypermethylation is a frequent event in laryngeal and hypopharyngeal cancer, but it is not a predictor of mortality or second primary cancer.

[Association between microsatellite instability and clinico-pathological characteristics in sporadic colon cancer]. / Asociación entre la inestabilidad de microsatélites y las características clínicas y anatomopatológicas en pacientes con cáncer de colon esporádico.

BACKGROUND AND OBJECTIVE: Currently, colon cancer is a leading cause of cancer death world-wide. It progresses according to three molecular pathways, named suppressor, mutador and methylator. Microsatellite instability is a hallmark of the lack of reparation, of DNA mismatches and it characterizes a subset of colon tumors (unstable tumors, MSI). MSI-H patients (high degree of microsatellite instability) seem to share clinico-pathological differences with MSS (microsatellite stable) and MSI-L (low degree of microsatellite instability) patients. In this study, associations between high degree of microsatellite instability and pathological (location, mucinous content, differentiation grade, stages T3N0, stages II and III) and clinical features (response to chemotherapy, disease-free survival and overall survival) were evaluated. PATIENTS AND METHOD: 117 patients with sporadic colon cancer were classified into two populations (MSS/MSI-L and MSI-H) by using PCR and electrophoresis of seven microsatellites, according to the National Cancer Institute recommendations. RESULTS: MSI-H tumors tended to be located in the right colon (p = 0.022) and were of mucinous histologic type (p = 0.04). No differences in disease-free survival and overall survival between group of stage II and III patients with MSS/ MSI-L and corresponding ones with MSI-H colon cancer were found (p = 0.54, p = 0.37, respectively). Conversely, MSI-H patients with stage II colon cancer had a favourable prognosis (p = 0.027). Nevertheless, response to 5-fluorouracil (5-FU) and leucovorin was similar in MSS/ MSI-L and MSI-H groups (p = 0.38). CONCLUSIONS: MSI-H patients are characterized by certain pathological features; those MSI-H patients with a stage II seem to have a better prognosis than MSS/ MSI-L patients.

PTEN and DMBT1 homozygous deletion and expression in medulloblastomas and supratentorial primitive neuroectodermal tumors.

Medulloblastoma, which accounts for 20-25% of all childhood brain tumors, is defined as a primitive neuroectodermal tumor (PNET) located in the cerebellum. Supratentorial PNET are less frequent than medulloblastoma. But their clinical outcome is worse than in medulloblastomas. Chromosome 10q contains at least 2 tumor suppressor genes that might play a role in brain tumor development: PTEN and DMBT1. The aim of this study was to compare the status of homozygous deletion and expression of PTEN and DMBT1 genes in PNET primary tumor samples and cell lines. Homozygous deletions of PTEN and DMBT1 were studied in 32 paraffin-embedded PNET samples (23 medulloblastomas and 9 supratentorial PNET) and in 7 PNET cell lines, by differential PCR and by FISH. PTEN homozygous losses were demonstrated in 7 medulloblastomas (32%) and in no supratentorial PNET, while homozygous deletions of DMBT1 appeared in 1 supratentorial PNET (20%) and in 7 medulloblastomas (33%). No homozygous deletion of PTEN or DMBT1 was detected in any of the PNET cell lines either by differential PCR or by FISH. Expression study of the 2 genes was performed in the 7 PNET cell lines by RT-PCR. One PNET cell line lacked PTEN and DMBT1 expression, while 2 medulloblastoma cell lines did not express DMBT1. Our results add some positive data to the hypothesis that supratentorial PNETs and medulloblastomas might be genetically different.

Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q.

Various genomic alterations have been detected in glioblastoma. Chromosome 7p, with the epidermal growth factor receptor locus, together with chromosome 10q, with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent kinase inhibitor 2A locus, are among the most frequently damaged chromosomal regions in glioblastoma. In this study, we evaluated the genetic status of 32 glioblastomas by comparative genomic hybridization; the sensitivity of comparative genomic hybridization versus differential polymerase chain reaction to detect deletions at the phosphatase and tensin homologue deleted in chromosome 10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of genetic lesions (gain or loss) at 16 different selected loci (including oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13 different chromosomes; and the possible existence of a statistical association between any pair of molecular markers studied, to subdivide the glioblastoma entity molecularly. Comparative genomic hybridization showed that the most frequent region of gain was chromosome 7p, whereas the most frequent losses occurred on chromosomes 10q and 13q. The only statistically significant association was found for 7p gain and 10q loss.