Reduced Expression of SMAD4 Is Associated with Poor Survival in Colon Cancer.

PURPOSE: SMAD4 loss is associated with the development of metastases and poor prognosis. We evaluated expression of SMAD4 protein and its association with tumor characteristics, including biomarkers and outcome in terms of relapse-free survival and overall survival. EXPERIMENTAL DESIGN: We used 1,564 stage II/III colon cancer samples from PETACC-3 to evaluate SMAD4 expression by immunohistochemistry. SMAD4 protein expression was validated by assessing mRNA expression using available expression array data. SMAD4 expression was also studied on 34 adenomas and 10 colon cancer liver metastases with their primaries. Loss of SMAD4 immunoreactivity was defined as focal or diffuse. Cases without SMAD4 loss were subdivided into those with strong and weak expression. RESULTS: SMAD4 protein expression was informative in 1,381/1,564 cases. SMAD4 loss was found in 293/1,381 (21%) cases. Of 1,088 cases without SMAD4 loss (79%), 530 showed weak and 558 strong expression. SMAD4 loss occurred also in adenomas, but less extensively than in carcinomas. Liver metastases followed mostly the expression pattern of the primary tumor. SMAD4 loss, including weak expression, identified patients with poor survival in stage II as well as III and in both treatment arms. SMAD4 loss was less frequent in tumors with microsatellite instability and more frequent in those with loss of heterozygosity of 18q. CONCLUSIONS: We conclude that clonal loss of SMAD4 expression in adenomas, carcinomas, and liver metastases increases with disease progression. SMAD4 loss, and to a lesser extent weak expression, is strongly associated with poor survival regardless of stage. Clin Cancer Res; 22(12); 3037-47. ©2016 AACR.

Human papillomavirus genotype distribution among Cameroonian women with invasive cervical cancer: a retrospective study.

OBJECTIVES: We determined the human papillomavirus (HPV) types present in invasive cervical cancer (ICC) of women in Cameroon in order to estimate the potential efficacies of HPV prophylactic vaccines. METHODS: This is a retrospective study using 181 formalin-fixed paraffin-embedded cervical tissue samples of ICC collected from the Institute of Pathology, Gyneco-Obstetric and Pediatric Hospital, Yaoundé, Cameroon. HPV was detected by PCR using modified GP5+/GP6+ (MGP) primers. Genotyping was performed by reverse-blot hybridisation, which allowed the detection of 9 of the 14 high-risk HPV types. RESULTS: Of the 181 samples, 91.7% were squamous cell carcinomas and 6.6% were adenocarcinomas. Counting all the single and multiple infections, the three most common high-risk types in descending order were HPV16 (88%), HPV45 (32%) and HPV18 (14.8%). 54.9% of cases were infected with a single HPV type and 45.1% had two or more HPV infections. CONCLUSIONS: The frequencies of HPV16, HPV45 and multiple infections are all higher than previously reported. These observations have significant implications on the consideration of vaccination strategies because each vaccine has different duration and efficacies in cross-protection of different HPV types. The method used proved to be sensitive and cost-efficient for retrospective studies where fresh materials are not available.

Kidney light chain disease in patients with the acquired immunodeficiency syndrome.

Light chain deposit disease (LCDD) is a rare condition caused by deposition of overproduced monoclonal light chains and has been frequently related to multiple myeloma or lymphocytic disorders. LCDD in association with human immunodeficiency virus (HIV) has only been described twice in the literature and is thought to result from HIV direct/indirect effects on B and T-cell populations, leading to chronic immune activation with paraprotein production. We report a renal LCDD case diagnosed at autopsy in a severely immunodepressed HIV patient and analyse renal histopathology of 18 HIV patients who had an autopsy in our department between 2000 and 2010.

Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.

Infants with severe primary combined immunodeficiency (SCID) and children post-allogeneic hematopoietic stem cell transplantation (HSCT) are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA) techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients.