Expression of HER2 and bradykinin B1 receptors in precursor lesions of gallbladder carcinoma.

AIM: To determine the expression of HER2 and bradykinin B(1) receptors (B(1)R) in the two pathogenic models of gallbladder cancer: the metaplasia-dysplasia-carcinoma and the adenoma-carcinoma pathways. METHODS: Receptor proteins were visualized by immunohistochemistry on 5-µm sections of paraffin-embedded tissue. Expression of both receptors was studied in biopsy samples from 92 patients (6 males and 86 females; age ranging from 28 to 86 years, mean 56 years). High HER2 expression in specimens was additionally investigated by fluorescence in situ hybridization. Cell proliferation in each sample was assessed by using the Ki-67 proliferation marker. RESULTS: HER2 receptor protein was absent in adenomas and in normal gallbladder epithelium. On the contrary, there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia (22/24; 91.7%) and carcinoma in situ (9/10; 90%), the lesions that displayed a significantly high proliferation index. Protein up-regulation of HER2 in the epithelium with metaplasia or carcinoma in situ was not accompanied by HER2 gene amplification. A similar result was observed in invasive carcinomas (0/12). The B(1)R distribution pattern mirrored that of HER2 except that B(1)R was additionally observed in the adenomas. The B(1)R appeared either as cytoplasmic dots or labeling on the apical cell membrane of the cells composing the epithelia with intestinal metaplasia (24/24; 100%) and carcinoma in situ (10/10; 100%) and in the epithelial cells of adenomas. In contrast, both HER2 (4/12; 33%) and B(1)R (1/12; 8.3%) showed a low expression in invasive gallbladder carcinomas. CONCLUSION: The up-regulation of HER2 and B(1)R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis.

[Cytogenetic and molecular profile of genetic diseases in Puerto Montt main hospital]. / Caracterización citogenético-molecular de enfermedades genéticas en el Hospital Base de Puerto Montt.

BACKGROUND: Chromosome aberrations (CA) are the main etiology of multiple congenital malformations, recurrent abortions and intellectual disability (ID) specifically of moderate and severe degree. They account for 0.3 to 1% of newborns (NB) and 6 of 10,000 NB have chromosome imbalances with submicroscopic deletions or duplications smaller than 10 MB that are overlooked by conventional cytogenetic studies. AIM: To report the results of cytogenetic and molecular studies performed in patients with a congenital malformation disease or ID with or without dysmorphic features, attended in a regional hospital. PATIENTS AND METHODS: One hundred and eighty patients, 27 with a clinical diagnosis of Down syndrome, derived for the suspicion of a genetic disease, were studied. A karyogram was performed in all of them and in 30 cases additional molecular studies, such as fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) were carried out. RESULTS: Among the 153 patients without Down syndrome, 20 (13%) had a genetic abnormality responsible for the altered phenotype. Sixteen had a chromosome aberration (structural and numerical aberrations in 75 and 25% respectively) and four had genetic molecular alterations. Additional studies were performed to confirm or better characterize the chromosome aberration in 13 of the 30 patients in whom these were requested. CONCLUSIONS: Chromosome and specific genetic molecular studies in selected cases help to characterize patients with genetic diseases. The collaboration between academic and health care facilities is crucial.

Caracterización citogenético-molecular de enfermedades genéticas en el Hospital Base de Puerto Montt / Cytogenetic and molecular profile of genetic diseases in Puerto Montt main hospital

Background: Chromosome aberrations (CA) are the main etiology of múltiple congenital malformations, recurrent abortions and intellectual disability (ID) specifically of modérate and severe degree. They accountfor 0.3 to 1 percent of newborns (NB) and 6 of 10,000 NB have chromosome imbalances with submicroscopic deletions or duplications smaller than 10 MB that are overlooked by conventional cytogenetic studies. Aim: To report the results of cytogenetic and molecular studies performed in patients with a congenital malformation disease or ID with or without dysmorphic features, attended in a regional hospital. Patients and Methods: One hundred and eighty patients, 27 with a clinical diagnosis ofDown syndrome, derivedfor the sus-picion of a genetic disease, were studied. A karyogram was performed in all ofthem and in 30 cases additional molecular studies, such as fluorescence in situ hybridization (FISH) orpolymerase chain reaction (PCR) were carried out. Results: Amongthe 153 patients without Down syndrome, 20 (13 percent) had a genetic abnormality responsible for the altered phenotype. Sixteen had a chromosome aberration (structural and numerical aberrations in 75 and 25 percent respectively) andfour had genetic molecular alterations. Additional studies were performed to confirm or better characterize the chromosome aberration in 13 ofthe 30 patients in whom these were requested. Conclusions: Chromosome and specific genetic molecular studies in selected cases help to characterize patients with genetic diseases. The collaboration between academic and health care facilities is crucial.