Исторические факты о первой в мире клинической постмортальной эксплантации и последующей аллогенной гетеротопной трансплантации донорской почки: легендарные страницы жизни выдающегося хирурга Ю. Вороного

АЛЛОТРАНСПЛАНТАЦИЯПОЧЕК ТРАНСПЛАНТАЦИЯ /истКСЕНОТРАНСПЛАНТАЦИЯИСТОРИЯ МЕДИЦИН

Микрохирургическая техника комбинированной трансплантации поджелудочной железы и почки в экспериментальной модели

ПОДЖЕЛУДОЧНАЯ ЖЕЛЕЗА /хирПОЧКИ /хирТРАНСПЛАНТАЦИЯаллографтхирургические техник

Микрохирургическая техника комбинированной трансплантации поджелудочной железы и почки в экспериментальной модели

ПОДЖЕЛУДОЧНАЯ ЖЕЛЕЗА /хирПОЧКИ /хирТРАНСПЛАНТАЦИЯаллографтхирургические техник

FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer

625 Background: Bange et al. recently found that a single-nucleotide polymorphism (SNP) at codon 388 of fibroblast growth factor receptor 4 (FGFR4) gene, causing a transmembrane domain missense mutation (Gly388Arg), is associated with outcome in node-positive breast cancer. Methods: This study addresses clinical relevance of this SNP, FGFR4 genotype, phenotype, and HER2 regarding patient outcome and influence of adjuvant systemic therapy in a substantial primary breast cancer collective (n=372; 1987–2002), median follow-up 94.5 months. Treatment was administered according to consensus recommendations at the time: 73 patients (all N0) received no adjuvant systemic therapy; 114 received adjuvant chemotherapy (87% CMF-based), 164 tamoxifen, 10 combined chemo-endocrine therapy, 11 unknown. 128 (36%) patients experienced disease recurrence, 104 (81%) distant relapses; 140 (38%) died. PCR-RFLP-analysis of germ-line polymorphism was performed in uninvolved lymph nodes; FGFR4 and HER2 expression were assessed immunohistochemically in tumor tissue arrays. Primary endpoint was DFS, since it best reflects impact of adjuvant systemic therapy. Results: In 51% of patients, homo- or heterozygous Arg388 allele was present. No correlation existed between FGFR4 genotype and expression or HER2 status. In N0 patients, FGFR4 genotype was not correlated with disease outcome. In N+ patients, however, FGFR4 Arg388 was significantly associated with poor DFS (p=0.02) and OS (p=0.04). Notably, this association seems to be attributable to relatively poor therapy response in Arg388 carriers, reflected in their significantly shorter DFS (p=0.02) and OS (p=0.045) among patients receiving adjuvant systemic therapy. It is also seen as a significant interaction term in a multivariate proportional hazards model with Arg388 carriers having only about half as much benefit from adjuvant systemic therapy as wild-type carriers. Conclusions: Our results show that the previously found association of FGFR4 Arg388 genotype with breast cancer progression is strongest in patients with adjuvant systemic therapy, particularly chemotherapy, and thus may reflect therapy resistance. No significant financial relationships to disclose. </jats:p

Prognostic significance of expression patterns of c‐erbB‐2, p53, p16(INK4A), p27(KIP1), cyclin D1 and epidermal growth factor receptor in oesophageal adenocarcinoma: a tissue microarray study

AIMS: To correlate immunohistochemical expression patterns and prognosis in oesophageal adenocarcinoma. METHODS: The expression of c‐erbB‐2, p53, p16(INK4A), p27(KIP1), cyclin D1 and epidermal growth factor receptor (EGFR) was studied in a series of 137 primarily resected oesophageal adenocarcinoma samples. The expression analysis on protein level was performed on routine paraffin wax‐embedded material, with immunohistochemical staining of the samples, assembled on a tissue microarray. The results were correlated with clinicopathological features (pT, pN and G) and survival. RESULTS: 22 (16%) tumours showed an overexpression of the c‐erbB‐2 oncoprotein. Expression of EGFR was observed in 72 (55%) cases, accumulation of p53 in 68 (52%) cases and of cyclin D1 in 102 (77%) cases. Loss of p16(INK4A) expression was observed in 101 (76%) cases and low expression of p27(KIP1) in 91 (71%) cases. Expression of these proteins did not correlate with tumour stage, grade, Lauren's or World Health Organization classification or lymph node status. On univariate survival analysis, more advanced tumour stage (p = 0.002), lymph node involvement (p = 0.003), high tumour grade (p = 0.017) and lack of EGFR expression (p = 0.034) were found to be associated with poorer survival. On multiple regression analysis, only tumour stage (p = 0.03) and lymph node involvement (p = 0.004) were shown to have an association with the survival of the patient. CONCLUSION: The immunohistochemical expression of c‐erbB‐2 oncoprotein, cylin D1, p16(INK4A), p27(KIP1), p53 and EGFR in most oesophageal adenocarcinomas suggests their implication in the pathogenesis of this entity. None of the molecular markers assessed, however, was of prognostic value. Identification of any marker superior to or even approaching the prognostic value of conventional histopathological markers (pT and pN) was therefore not possible